Pipes Output http://pipes.yahoo.com/pipes/pipe.info?_id=wKB6qta72xGqBxWCkAtvUw Sat, 28 Nov 2009 16:01:25 -0800 http://pipes.yahoo.com/pipes/ http://pubs.acs.org/doi/abs/10.1021/pr9009518?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/0/jprobs.ahead-of-print/pr9009518/images/medium/pr-2009-009518_0003.gif"/>Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). José María Gutiérrez et al http://pubs.acs.org/doi/abs/10.1021/pr9009518?ai=52c&af=R Tue, 24 Nov 2009 08:55:39 -0800 article http://pubs.acs.org/doi/abs/10.1021/pr900721e?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/0/jprobs.ahead-of-print/pr900721e/images/medium/pr-2009-00721e_0007.gif"/>Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Peter Mortensen et al http://pubs.acs.org/doi/abs/10.1021/pr900721e?ai=52c&af=R Wed, 18 Nov 2009 09:51:53 -0800 article http://pubs.acs.org/doi/abs/10.1021/pr900864s?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/0/jprobs.ahead-of-print/pr900864s/images/medium/pr-2009-00864s_0004.gif"/>Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Junmei Zhang et al http://pubs.acs.org/doi/abs/10.1021/pr900864s?ai=52c&af=R Mon, 16 Nov 2009 08:36:44 -0800 article http://pubs.acs.org/doi/abs/10.1021/pr900738b?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/0/jprobs.ahead-of-print/pr900738b/images/medium/pr-2009-00738b_0002.gif"/>Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Fengguo Xu et al http://pubs.acs.org/doi/abs/10.1021/pr900738b?ai=52c&af=R Fri, 30 Oct 2009 09:10:48 -0700 article http://pubs.acs.org/doi/abs/10.1021/pr900711j?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/0/jprobs.ahead-of-print/pr900711j/images/medium/pr-2009-00711j_0007.gif"/>Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Yulan Wang et al http://pubs.acs.org/doi/abs/10.1021/pr900711j?ai=52c&af=R Wed, 28 Oct 2009 12:06:25 -0700 article http://pubs.acs.org/doi/abs/10.1021/pr900668v?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/0/jprobs.ahead-of-print/pr900668v/images/medium/pr-2009-00668v_0001.gif"/>Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Joanna Teul et al http://pubs.acs.org/doi/abs/10.1021/pr900668v?ai=52c&af=R Wed, 28 Oct 2009 12:05:44 -0700 article http://pubs.acs.org/doi/abs/10.1021/pr900158n?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/0/jprobs.ahead-of-print/pr900158n/images/medium/pr-2009-00158n_0001.gif"/>Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Hong Wang et al http://pubs.acs.org/doi/abs/10.1021/pr900158n?ai=52c&af=R Mon, 26 Oct 2009 13:55:16 -0700 article http://pubs.acs.org/doi/abs/10.1021/pr900593r?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/0/jprobs.ahead-of-print/pr900593r/images/medium/pr-2009-00593r_0005.gif"/>Journal of Proteome Research, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Fu Yang et al http://pubs.acs.org/doi/abs/10.1021/pr900593r?ai=52c&af=R Thu, 08 Oct 2009 11:33:02 -0700 article http://pubs.acs.org/doi/abs/10.1021/pr900252n?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/2009/jprobs.2009.8.issue-11/pr900252n/images/medium/pr-2009-00252n_0003.gif"/>Journal of Proteome Research, Volume 8, Issue 11, Page 4934-4942, November 2009. Aihua Sun et al http://pubs.acs.org/doi/abs/10.1021/pr900252n?ai=52c&af=R Thu, 05 Nov 2009 22:43:54 -0800 article http://pubs.acs.org/doi/abs/10.1021/pr9007267?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/2009/jprobs.2009.8.issue-11/pr9007267/images/medium/pr-2009-007267_0004.gif"/>Journal of Proteome Research, Volume 8, Issue 11, Page 4954-4965, November 2009. Kurt Højlund et al http://pubs.acs.org/doi/abs/10.1021/pr9007267?ai=52c&af=R Thu, 05 Nov 2009 21:15:30 -0800 article http://pubs.acs.org/doi/abs/10.1021/pr900452s?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/2009/jprobs.2009.8.issue-11/pr900452s/images/medium/pr-2009-00452s_0010.gif"/>Journal of Proteome Research, Volume 8, Issue 11, Page 5031-5040, November 2009. Xichun Zhou et al http://pubs.acs.org/doi/abs/10.1021/pr900452s?ai=52c&af=R Thu, 05 Nov 2009 21:45:00 -0800 article http://pubs.acs.org/doi/abs/10.1021/pr900470a?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/2009/jprobs.2009.8.issue-11/pr900470a/images/medium/pr-2009-00470a_0004.gif"/>Journal of Proteome Research, Volume 8, Issue 11, Page 5060-5068, November 2009. Rafael Llorach et al http://pubs.acs.org/doi/abs/10.1021/pr900470a?ai=52c&af=R Thu, 05 Nov 2009 21:47:24 -0800 article http://pubs.acs.org/doi/abs/10.1021/pr900489m?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/2009/jprobs.2009.8.issue-11/pr900489m/images/medium/pr-2009-00489m_0005.gif"/>Journal of Proteome Research, Volume 8, Issue 11, Page 5120-5131, November 2009. Teresa Escalante et al http://pubs.acs.org/doi/abs/10.1021/pr900489m?ai=52c&af=R Thu, 05 Nov 2009 21:13:42 -0800 article http://pubs.acs.org/doi/abs/10.1021/pr900569d?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/2009/jprobs.2009.8.issue-11/pr900569d/images/medium/pr-2009-00569d_0003.gif"/>Journal of Proteome Research, Volume 8, Issue 11, Page 5229-5240, November 2009. Antonio Bastone et al http://pubs.acs.org/doi/abs/10.1021/pr900569d?ai=52c&af=R Thu, 05 Nov 2009 21:24:09 -0800 article http://pubs.acs.org/doi/abs/10.1021/pr900580n?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/2009/jprobs.2009.8.issue-11/pr900580n/images/medium/pr-2009-00580n_0004.gif"/>Journal of Proteome Research, Volume 8, Issue 11, Page 5241-5252, November 2009. Hanne Lund et al http://pubs.acs.org/doi/abs/10.1021/pr900580n?ai=52c&af=R Thu, 05 Nov 2009 22:46:28 -0800 article http://pubs.acs.org/doi/abs/10.1021/pr900610q?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/2009/jprobs.2009.8.issue-11/pr900610q/images/medium/pr-2009-00610q_0010.gif"/>Journal of Proteome Research, Volume 8, Issue 11, Page 5275-5284, November 2009. Timothy Clough et al http://pubs.acs.org/doi/abs/10.1021/pr900610q?ai=52c&af=R Thu, 05 Nov 2009 22:42:05 -0800 article http://pubs.acs.org/doi/abs/10.1021/pr900557k?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/2009/jprobs.2009.8.issue-11/pr900557k/images/medium/pr-2009-00557k_0006.gif"/>Journal of Proteome Research, Volume 8, Issue 11, Page 5317-5324, November 2009. Benjamin Rietschel et al http://pubs.acs.org/doi/abs/10.1021/pr900557k?ai=52c&af=R Thu, 05 Nov 2009 22:45:07 -0800 article http://pubs.acs.org/doi/abs/10.1021/pr900564f?ai=52c&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/jprobs/2009/jprobs.2009.8.issue-11/pr900564f/images/medium/pr-2009-00564f_0003.gif"/>Journal of Proteome Research, Volume 8, Issue 11, Page 5387-5395, November 2009. Jian-Ying Zhou et al http://pubs.acs.org/doi/abs/10.1021/pr900564f?ai=52c&af=R Thu, 05 Nov 2009 22:51:20 -0800 article http://xlink.rsc.org/?DOI=b913212k&RSS=1 Lithium-doped silicon nanowires (SiNW) have been used for sensitive detection of neutral lipids by laser-assisted desorption/ionization mass spectrometry (LDI-TOF/MS) for the first time. Those micro-fabricated SiNW chips should find wide application in food control and medicine. wKB6qta72xGqBxWCkAtvUw_6d6bab247c66338c66109d7ad1349d8f Thu, 19 Nov 2009 00:00:00 -0800

Alexander Muck, Thomas Stelzner, Uwe Hubner, Silke Christiansen, Ales Svatos
(Paper from Lab Chip)
Alexander Muck, Lab Chip, 2010, DOI: 10.1039/b913212k
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The content of this RSS Feed (c) The Royal Society of Chemistry]]> http://xlink.rsc.org/?DOI=b914874d&RSS=1 We present a microfluidic chip that is capable of generating complex patterns of shear flow, to study sensory and force transduction mechanisms in cells. wKB6qta72xGqBxWCkAtvUw_3840d9584b02d663e7bd42fc8020a42e Tue, 17 Nov 2009 00:00:00 -0800

Jianbin Wang, Jinseok Heo, Susan Z. Hua
(Paper from Lab Chip)
Jianbin Wang, Lab Chip, 2010, DOI: 10.1039/b914874d
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The content of this RSS Feed (c) The Royal Society of Chemistry]]> http://xlink.rsc.org/?DOI=b911113a&RSS=1 By using a single focusing low-resolution MC-ICP-MS equipped with a hexapole gas-collision cell (Helium), we can precisely and accurately measure the [small delta]29Si (2S.D., 0.2[per thousand]) with a total Si consumption of less than 14 nmol (390 ng Si). wKB6qta72xGqBxWCkAtvUw_830d2bc825c843b8fda733a888a2c5c8 Wed, 25 Nov 2009 00:00:00 -0800

Xiaole Sun, Per Andersson, Magnus Land, Christoph Humborg, Carl-Magnus Morth
(Paper from J. Anal. At. Spectrom.)
Xiaole Sun, J. Anal. At. Spectrom., 2010, DOI: 10.1039/b911113a
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The content of this RSS Feed (c) The Royal Society of Chemistry]]> http://xlink.rsc.org/?DOI=b917008a&RSS=1 The homogeneity of plastic reference materials containing Br, Cd, Cr, Hg and Pb was investigated. Their suitability for XRF and LA-ICP-MS has been shown. wKB6qta72xGqBxWCkAtvUw_7075a42a8fca607cb2579be1d91ecdf0 Thu, 19 Nov 2009 00:00:00 -0800

Christoph Simons, Christian Mans, Stephanie Hanning, Anton Jan[German sz ligature}en, Martin Radtke, Uwe Reinholz, Markus Ostermann, Matthias Michaelis, Julia Wienold, Dorothea Alber, Martin Kreyenschmidt
(Paper from J. Anal. At. Spectrom.)
Christoph Simons, J. Anal. At. Spectrom., 2010, DOI: 10.1039/b917008a
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The content of this RSS Feed (c) The Royal Society of Chemistry]]> http://xlink.rsc.org/?DOI=b912605h&RSS=1 An original method for the resolution of the Eu-Gd-Sm isobaric interference with a collision/reaction cell of an MC-ICP-MS has been developed. The aim of this work is to perform Eu isotopic ratio measurements of irradiated nuclear samples. wKB6qta72xGqBxWCkAtvUw_0aebab4551dbd558c8684b5cdf2d0354 Wed, 11 Nov 2009 00:00:00 -0800

F. Gueguen, A. Nonell, M. Granet, G. Favre, H. Isnard, F. Chartier
(Technical Note from J. Anal. At. Spectrom.)
F. Gueguen, J. Anal. At. Spectrom., 2010, DOI: 10.1039/b912605h
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The content of this RSS Feed (c) The Royal Society of Chemistry]]> http://xlink.rsc.org/?DOI=b911696f&RSS=1 A simple method for mercury speciation in hair samples with a fast sample preparation procedure using high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry is proposed. wKB6qta72xGqBxWCkAtvUw_1d9cd7edf50c893e84edfcfdf3389607 Mon, 02 Nov 2009 00:00:00 -0800

Samuel S. de Souza, Jairo L. Rodrigues, Vanessa C. de Oliveira Souza, Fernando Barbosa Jr.
(Technical Note from J. Anal. At. Spectrom.)
Samuel S. de Souza, J. Anal. At. Spectrom., 2010, DOI: 10.1039/b911696f
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The content of this RSS Feed (c) The Royal Society of Chemistry]]> http://pubs.acs.org/doi/abs/10.1021/ac902005s?ai=54k&af=R Analytical Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Graeme C. McAlister et al http://pubs.acs.org/doi/abs/10.1021/ac902005s?ai=54k&af=R Wed, 25 Nov 2009 07:49:45 -0800 article http://pubs.acs.org/doi/abs/10.1021/ac9015648?ai=54k&af=R Analytical Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Jacek P. Dworzanski et al http://pubs.acs.org/doi/abs/10.1021/ac9015648?ai=54k&af=R Wed, 25 Nov 2009 07:36:15 -0800 article http://pubs.acs.org/doi/abs/10.1021/ac902250p?ai=54k&af=R Analytical Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Jeffrey J. Lange et al http://pubs.acs.org/doi/abs/10.1021/ac902250p?ai=54k&af=R Mon, 23 Nov 2009 06:03:15 -0800 article http://pubs.acs.org/doi/abs/10.1021/ac901635q?ai=54k&af=R Analytical Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Andrew D. Pris et al http://pubs.acs.org/doi/abs/10.1021/ac901635q?ai=54k&af=R Mon, 16 Nov 2009 08:58:01 -0800 article http://pubs.acs.org/doi/abs/10.1021/ac9015853?ai=54k&af=R Analytical Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Besnik Bajrami et al http://pubs.acs.org/doi/abs/10.1021/ac9015853?ai=54k&af=R Wed, 11 Nov 2009 11:48:54 -0800 article http://pubs.acs.org/doi/abs/10.1021/ac901594f?ai=54k&af=R Analytical Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Francisco A. Fernandez-Lima et al http://pubs.acs.org/doi/abs/10.1021/ac901594f?ai=54k&af=R Wed, 11 Nov 2009 11:24:20 -0800 article http://pubs.acs.org/doi/abs/10.1021/ac901498k?ai=54k&af=R Analytical Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Oleg V. Borisov et al http://pubs.acs.org/doi/abs/10.1021/ac901498k?ai=54k&af=R Tue, 10 Nov 2009 09:46:35 -0800 article http://pubs.acs.org/doi/abs/10.1021/ac9024494?ai=54k&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/ancham/0/ancham.ahead-of-print/ac9024494/images/medium/ac-2009-024494_0002.gif"/>Analytical Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Rajendrani Mukhopadhyay http://pubs.acs.org/doi/abs/10.1021/ac9024494?ai=54k&af=R Mon, 09 Nov 2009 07:17:17 -0800 article http://pubs.acs.org/doi/abs/10.1021/ac901663x?ai=54k&af=R Analytical Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Xiao-Yan Cui et al http://pubs.acs.org/doi/abs/10.1021/ac901663x?ai=54k&af=R Fri, 06 Nov 2009 07:52:42 -0800 article http://pubs.acs.org/doi/abs/10.1021/ac9020243?ai=54k&af=R Analytical Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Mrinal K. Sengupta et al http://pubs.acs.org/doi/abs/10.1021/ac9020243?ai=54k&af=R Thu, 05 Nov 2009 10:12:27 -0800 article http://pubs.acs.org/doi/abs/10.1021/ac901595b?ai=54k&af=R Analytical Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Sara E. Andria et al http://pubs.acs.org/doi/abs/10.1021/ac901595b?ai=54k&af=R Thu, 05 Nov 2009 10:04:43 -0800 article http://pubs.acs.org/doi/abs/10.1021/ac9024285?ai=54k&af=R <img src="http://pubs.acs.org//appl/literatum/publisher/achs/journals/production/ancham/0/ancham.ahead-of-print/ac9024285/images/medium/ac-2009-024285_0002.gif"/>Analytical Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Erika Gebel http://pubs.acs.org/doi/abs/10.1021/ac9024285?ai=54k&af=R Fri, 30 Oct 2009 06:21:38 -0700 article http://pubs.acs.org/doi/abs/10.1021/ac901363h?ai=54k&af=R Analytical Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). John A. Goetz et al http://pubs.acs.org/doi/abs/10.1021/ac901363h?ai=54k&af=R Thu, 29 Oct 2009 10:13:19 -0700 article http://pubs.acs.org/doi/abs/10.1021/ac901510s?ai=54k&af=R Analytical Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). Longhua Guo et al http://pubs.acs.org/doi/abs/10.1021/ac901510s?ai=54k&af=R Tue, 10 Nov 2009 09:47:19 -0800 article http://pubs.acs.org/doi/abs/10.1021/ac9018796?ai=54k&af=R Analytical Chemistry, Volume 81, Issue 22, Page 9454-9461, November 15, 2009. Michel Boutin et al http://pubs.acs.org/doi/abs/10.1021/ac9018796?ai=54k&af=R Thu, 12 Nov 2009 21:14:25 -0800 article http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=19942451&dopt=Abstract <table border="0" width="100%"><tr><td align="left"></tr></table><p><b>What Does the Future Hold for Top Down Mass Spectrometry?</b></p> <p>J Am Soc Mass Spectrom. 2009 Oct 29;</p> <p>Authors: Garcia BA</p> <p>Mass spectrometry (MS) research has revolutionized modern biological and biomedical fields. At the heart of the majority of mass spectrometry experiments is the use of Bottom Up mass spectrometry methods where proteins are first proteolyzed into smaller fragments before MS interrogation. The advent of electron capture dissociation and, more recently, electron-transfer dissociation, however, has allowed Top Down (analysis of intact proteins) or middle down (analysis of large polypeptides) mass spectrometry to both experience large increases in development, growth, and overall usage. Nevertheless, for high-throughput large-scale proteomic studies, Bottom Up mass spectrometry has easily dominated the field. As Top Down mass spectrometry methodology and technology continue to develop, will it genuinely be able to compete with Bottom Up mass spectrometry for whole proteome analysis? Discussed here are the current approaches, applications, issues, and future view of high-throughput Top Down mass spectrometry.</p> <p>PMID: 19942451 [PubMed - as supplied by publisher]</p> Garcia BA PubMed:19942451 J Am Soc Mass Spectrom http://www.hubmed.org/display.cgi?uids=19802340 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=19802340">Int J Mass Spectrom</a>. 2008 Oct 1; 276(2-3): 110-115<br>Leach FE, Wolff JJ, Laremore TN, Linhardt RJ, Amster IJ<p>The efficiency of conversion of precursor ions to observable products for electron detachment dissociation (EDD) was measured as a function of the key experimental parameters to determine their optimal values for the Fourier transform mass spectrometry analysis of anionic glycosaminoglycan carbohydrates. These parameters include electron current, electron energy, dispenser cathode heater current, electron beam duration, charge state of the precursor ion, oligomer length, and precursor ion number accumulated in an external radio frequency multipole trap. Precursor conversion is most efficient at an electron current of 15 microA, and decreases at higher and lower values. The conversion of precursor to product ions increases in efficiency as the electron pulse duration is increased. Together, these data suggest that a radially repulsive electric field is produced between the electron beam and negative ions during EDD which causes the reaction cross section to decrease at higher values of electron current (&gt;15 microA). Elevating the heater current of the dispenser cathode increases the electron flux, but also causes ion activation, presumably by blackbody infrared irradiation. An electronic circuit is described that allows the electron current produced by the dispenser cathode to be measured during an EDD or electron capture dissociation (ECD) experiment. http://www.hubmed.org/display.cgi?uids=19802340 http://www.hubmed.org/display.cgi?uids=19802328 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=19802328">Int J Mass Spectrom</a>. 2008 Oct 1; 276(2-3): 136-143<br>Frey BL, Krusemark CJ, Ledvina AR, Coon JJ, Belshaw PJ, Smith LM<p>Electrospray ionization (ESI) of denatured proteins produces a mass spectrum with a broad distribution of multiply charged ions. Attaching fixed positive charges, specifically quaternary ammonium groups, to proteins at their carboxylic acid groups generates substantially higher charge states compared to the corresponding unmodified proteins in positive-mode ESI. Ion-ion reactions of these modified proteins with reagent anions leads to charge reduction by proton transfer. These proton transfer reactions cannot remove charge from the quaternary ammonium groups, which do not have a proton to transfer to the anion. Thus, one might expect charge reduction to stop at a single charge state equal to the number of fixed charges on the modified protein. However, ion-ion reactions yield charge states lower than this number of fixed charges due to anion attachment (adduction) to the proteins. Charge reduction via ion-molecule reactions involving gas-phase bases also give adducts on the modified protein ions in low charge states. Such adducts are avoided by keeping the ions in charge states well above the number of fixed charges. In the present work protein ions were selectively "parked" within an ion trap mass spectrometer in a high charge state by mild radiofrequency excitation that dramatically slows their ion-ion reaction rate-a technique termed "ion parking". The combination of ion parking with the fixed-charge modified proteins permits generation of a large population of ions in a single, very high charge state. http://www.hubmed.org/display.cgi?uids=19802328 http://www.hubmed.org/display.cgi?uids=19424441 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=19424441">Int J Mass Spectrom</a>. 2008 Oct 1; 276(2-3): 149-152<br>McAlister GC, Kiessel SE, Coon JJ<p>Here we report on the reaction of rhenate anions (ReO(3) (-)) with multiply protonated peptide cations in a quadrupole linear ion trap mass spectrometer. These reactions effect the formation of an anion-cation complex that, upon collisional activation, dissociates along the peptide backbone rather than by displacement of the anion. Cleavage of the peptide backbone, with anion retention, leads us to conclude the anion-cationcomplexmust be tightly bound, most probably through coordination chemistry. We describe this chemistry and detail the possible application of such ion attachment reactions to the characterization of intact proteins. http://www.hubmed.org/display.cgi?uids=19424441 http://www.hubmed.org/display.cgi?uids=19050741 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=19050741">Int J Mass Spectrom</a>. 2007 Dec 1; 268(2-3): 227-233<br>Johnson JD, Henriquez RR, Tichy SE, Russell DH, McNeal CJ, Macfarlane RD<p>The purpose of this study is to determine whether the nature of the post-translational modifications of the major apolipoproteins of HDL is different for density-distinct subclasses. These subclasses were separated by ultracentrifugation using a novel density-forming solute to yield a high-resolution separation. The serum of two subjects, a control with a normolipidemic profile and a subject with diagnosed cardiovascular disease, was studied. Aliquots of three HDL subclasses were analyzed by MALDI and considerable differences were seen when comparing density-distinct subclasses and also when comparing the two subjects. A detailed analysis of the post-translational modification pattern of apoA-1 shows evidence of considerable protease activity, particularly in the more dense fractions. We conclude that part of the heterogeneity of the population of HDL particles is due to density-dependent protease activity. http://www.hubmed.org/display.cgi?uids=19050741 http://www.hubmed.org/display.cgi?uids=19050733 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=19050733">Int J Mass Spectrom</a>. 2007 Dec 1; 268(2-3): 190-197<br>Whitelegge JP, Zabrouskov V, Halgand F, Souda P, Bassilian S, Yan W, Wolinsky L, Loo JA, Wong DT, Faull KF<p>Single nucleotide polymorphisms (SNPs) can result in protein sequence polymorphisms (PSPs) when codon translations are altered. Both top-down and bottom-up proteomics strategies can identify PSPs, but only if databases and software are used with this in mind. A 14319 Da protein from human saliva was characterized using the top-down approach on a hybrid linear ion-trap Fourier-transform ion cyclotron resonance mass spectrometer equipped for both collisionally-activated (CAD) and electron-capture (ECD) dissociation. Sequence tags identified the protein as Cystatin SN, and defined the N-terminal signal peptide cleavage site, as well as two disulfide bonds, in agreement with previous studies. The mass of the intact protein (&lt; 5 ppm error) deviated from that calculated from the published gene sequence by 16.031 Da, and, based on CAD and ECD fragment ion assignments, it was concluded that the isoform of the protein analyzed carried a PSP at residue 11 such that the Pro translated from the genome was in fact Leu/Ile. An independently determined SNP (rs2070856) subsequently confirmed the genetic basis of the mass spectral interpretation and defined the residue as Leu. In another example, the PRP3 protein with mass approximately 10,999 Da was found to be an isomeric/isobaric mixture of the reported sequence with PSPs D4N or D50N (rs1049112). Both CAD and ECD datasets support two phosphorylation sites at residues Ser8 and Ser22, rather than Ser17. In the context of discovery proteomics, previously undefined PSPs and PTMs will only be detected if the logic of data processing strategies considers their presence in an unbiased fashion. http://www.hubmed.org/display.cgi?uids=19050733 http://www.hubmed.org/display.cgi?uids=18802500 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=18802500">Int J Mass Spectrom</a>. 2006; 93-105<br>Herrmann KA, Kuppannan K, Wysocki VH<p>Doubly-protonated bradykinin (RPPGFSPFR) and an angiotensin III analogue (RVYIFPF) were subjected to hydrogen/deuterium (H/D) exchange with CD(3)OD in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. A bimodal distribution of deuterium incorporation was present for bradykinin after H/D exchange for 90 s at a CD(3)OD pressure of 4 x 10(-7) Torr, indicating the existence of at least two distinct populations. Bradykinin ion populations corresponding to 0-2 and 5-11 deuteriums (i.e., D(0), D(1), D(2), D(5), D(6), D(7), D(8), D(9), D(10), and D(11)) were each monoisotopically selected and fragmented via sustained off-resonance irradiation (SORI) collision-induced dissociation (CID). The D(0)-D(2) ion populations, which correspond to the slower exchanging population, consistently require lower SORI amplitude to achieve a similar precursor ion survival yield as the faster-reacting (D(5)-D(11)) populations. These results demonstrate that conformation/protonation motif has an effect on fragmentation efficiency for bradykinin. Also, the partitioning of the deuterium atoms into fragment ions suggests that the C-terminal arginine residue exchanges more rapidly than the N-terminal arginine. Total deuterium incorporation in the b(1)/y(8) and b(2)/y(7) ion pairs matches very closely the theoretical values for all ion populations studied, indicating that the ions of a complementary pair are likely formed during the same fragmentation event, or that no scrambling occurs upon SORI. Deuterium incorporation into the y(1)/a(8) pseudo-ion pair does not closely match the expected theoretical values. The other peptide, doubly-protonated RVYIFPF, has a trimodal distribution of deuterium incorporation upon H/D exchange with CD(3)OD at a pressure of 1 x 10(-7) Torr for 600 s, indicating at least three distinct ion populations. After 90 s of H/D exchange where at least two distinct populations are detected, the D(0)-D(7) ion populations were monoisotopically selected and fragmented via SORI-CID over a range of SORI amplitudes. The precursor ion survival yield as a function of SORI amplitude falls into two distinct behaviors corresponding to slower- and faster-reacting ion populations. The slower-reacting population requires larger SORI amplitudes to achieve the same precursor ion survival yield as the faster exchanging population. Total deuterium incorporation into the y(2)/b(5) ion pairs matches closely the theoretical values over all ion populations and SORI amplitudes studied. This result indicates the y(2) and b(5) ions are likely formed by the same mechanism over the SORI amplitudes studied. http://www.hubmed.org/display.cgi?uids=18802500 http://www.hubmed.org/display.cgi?uids=18347735 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=18347735">Int J Mass Spectrom</a>. 2007; 268: 93-105<br>Krutchinsky AN, Cohen H, Chait BT<p>We describe a prototype tandem mass spectrometer that is designed to increase the efficiency of linked-scan analyses by &gt;100-fold over conventional linked-scan instruments. The key element of the mass spectrometer is a novel high ion capacity ion trap, combined in tandem configuration with a quadrupole collision cell and a quadrupole mass analyzer (i.e. a TrapqQ configuration). This ion trap can store &gt;10(6) ions without significant degradation of its performance. The current mass resolution of the trap is 100-450 full width at half maximum for ions in the range 800-4000 m/z, yielding a 10-20 m/z selection window for ions ejected at any given time into the collision cell. The sensitivity of the mass spectrometer for detecting peptides is in the low femtomole range. We can envisage relatively straightforward modifications to the instrument that should improve both its resolution and sensitivity. We tested the tandem mass spectrometer for collecting precursor ion spectra of all the ions stored in the trap and demonstrated that we can selectively detect a phosphopeptide in a mixture of non-phosphorylated peptides. Based on this prototype instrument, we plan to construct a fully functional model of the mass spectrometer for detecting modification sites on proteins and profiling their abundances with high speed and sensitivity. http://www.hubmed.org/display.cgi?uids=18347735 http://www.hubmed.org/display.cgi?uids=18167512 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=18167512">Int J Mass Spectrom</a>. 2007 Jan 1; 259(1-3): 32-39<br>Engelhard VH<p>Over the last 15 years, the ability of mass spectrometry to analyze complex peptide mixtures and identify individual species has provided unprecedented insights into the repertoire of peptide antigens displayed by MHC molecules and recognized by T lymphocytes. These include: understanding the peptide binding specificity of MHC molecules; understanding of roles of different intracellular components of the antigen processing pathways in determining the peptide display; and identification of a large number of individual peptide antigens associated with infectious diseases, cancer, and transplant rejection that have provided the basis for new immunologically based therapies. This review will summarize the impact that the application of mass spectrometry has had on these advances, with particular attention to the contributions of Professor Donald Hunt and members of his laboratory, and point out the opportunities for future work. http://www.hubmed.org/display.cgi?uids=18167512 http://www.hubmed.org/display.cgi?uids=19430539 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=19430539">Int J Mass Spectrom</a>. 2007 Dec 1; 268(2-3): 304-315<br>Xie B, Luo X, Zhao C, Priest CM, Chan SY, O' Connor PB, Kirschner DA, Costello CE<p>Myelin protein zero (P0), a glycosylated single-pass transmembrane protein, is essential in the formation and maintenance of peripheral nervous system (PNS) compact myelin. P0 in Xenopus (xP0) exists primarily as a dimeric form that remains stable after various physical and chemical treatments. In exploring the nature of the interactions underlying the dimer stability, we found that xP0 dimer dissociated into monomer during continuous elution gel electrophoresis and conventional SDS-PAGE, indicating that the dimer is stabilized by non-covalent interactions. Furthermore, as some of the gel-purified monomer re-associated into dimer on SDS-PAGE gels, there is likely a dynamic equilibrium between xP0 dimer and monomer in vivo. Because the carbohydrate and fatty acyl moieties may be crucial for the adhesion role of P0, we used sensitive mass spectrometry approaches to elucidate the detailed N-glycosylation and S-acylation profiles of xP0. Asn92 was determined to be the single, fully-occupied glycosylation site of xP0, and a total of 12 glycans was detected that exhibited new structural features compared with those observed from P0 in other species: (1) the neutral glycans were composed mainly of high mannose and hybrid types; (2) five of twelve were acidic glycans, among which three were sialylated and the other two were sulfated; (3) none of the glycans had core fucosylation; and (4) no glucuronic acid, hence no HNK-1 epitope, was detected. The drastically different carbohydrate structures observed here support the concept of the species-specific variation in N-glycosylation of P0. Cys152 was found to be acylated with stearoyl (C18:0), whereas palmitoyl (C16:0) is the corresponding predominant fatty acyl group on P0 from higher vertebrates. We propose that the unique glycosylation and acylation patterns of Xenopus P0 may underlie its unusual dimerization behaviour. Our results should shed light on the understanding of the phylogenetic development of P0's adhesion role in PNS compact myelin. http://www.hubmed.org/display.cgi?uids=19430539 http://www.hubmed.org/display.cgi?uids=19562102 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=19562102">Int J Mass Spectrom</a>. 2007 Sep 1; 265(2-3): 99-105<br>Wong RL, Amster IJ<p>It is often stated that ions of the same mass-to-charge do not induce space-charge frequency shifts among themselves in an ion cyclotron resonance mass spectrometry measurement. Here, we demonstrate space-charge induced frequency shifts for ions of a single mass-to-charge. The monoisotopic atomic ion, Cs(+), was used for this study. The measured frequency is observed to decrease linearly with an increase in the number of ions, as has been reported previously for space-charge effects between ions of different mass-to-charge. The frequency shift between ions of the same m/z value are compared to that induced between ions of different m/z value, and is found to be 7.5 times smaller. Control experiments were performed to ensure that the observed space-charge effects are not artifacts of the measurement or of experimental design. The results can be rationalized by recognizing that the electric forces between ions in a magnetic field conform to the weak form of the Newton's third law, where the action and reaction forces do not cancel exactly. http://www.hubmed.org/display.cgi?uids=19562102 http://www.hubmed.org/display.cgi?uids=17541451 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=17541451">Int J Mass Spectrom</a>. 2007 Feb 1; 260(2-3): 212-221<br>Norris JL, Cornett DS, Mobley JA, Andersson M, Seeley EH, Chaurand P, Caprioli RM<p>Profiling and imaging biological specimens using MALDI mass spectrometry has significant potential to contribute to our understanding and diagnosis of disease. The technique is efficient and high-throughput providing a wealth of data about the biological state of the sample from a very simple and direct experiment. However, in order for these techniques to be put to use for clinical purposes, the approaches used to process and analyze the data must improve. This study examines some of the existing tools to baseline subtract, normalize, align, and remove spectral noise for MALDI data, comparing the advantages of each. A preferred workflow is presented that can be easily implemented for data in ASCII format. The advantages of using such an approach are discussed for both molecular profiling and imaging mass spectrometry. http://www.hubmed.org/display.cgi?uids=17541451 http://www.hubmed.org/display.cgi?uids=17375895 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=17375895">Int J Mass Spectrom</a>. 2007 Jan 1; 259(1-3): 147-160<br>Hu ZZ, Valencia JC, Huang H, Chi A, Shabanowitz J, Hearing VJ, Appella E, Wu C<p>Complete and accurate profiling of cellular organelle proteomes, while challenging, is important for the understanding of detailed cellular processes at the organelle level. Mass spectrometry technologies coupled with bioinformatics analysis provide an effective approach for protein identification and functional interpretation of organelle proteomes. In this study, we have compiled human organelle reference datasets from large-scale proteomic studies and protein databases for 7 lysosome-related organelles (LROs), as well as the endoplasmic reticulum and mitochondria, for comparative organelle proteome analysis. Heterogeneous sources of human organelle proteins and rodent homologs are mapped to human UniProtKB protein entries based on ID and/or peptide mappings, followed by functional annotation and categorization using the iProXpress proteomic expression analysis system. Cataloging organelle proteomes allows close examination of both shared and unique proteins among various LROs and reveals their functional relevance. The proteomic comparisons show that LROs are a closely related family of organelles. The shared proteins indicate the dynamic and hybrid nature of LROs, while the unique transmembrane proteins may represent additional candidate marker proteins for LROs. This comparative analysis, therefore, provides a basis for hypothesis formulation and experimental validation of organelle proteins and their functional roles. http://www.hubmed.org/display.cgi?uids=17375895 http://www.hubmed.org/display.cgi?uids=17364019 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=17364019">Int J Mass Spectrom</a>. 2007 Jan 1; 259(1-3): 197-203<br>Chi A, Bai DL, Geer LY, Shabanowitz J, Hunt DF<p>Direct analysis of intact proteins on a chromatographic time scale is demonstrated on a modified linear ion trap mass spectrometer using sequential ion/ion reactions, electron transfer and proton transfer, to dissociate the sample and to convert the resulting peptide fragments to a mixture of singly and doubly charged species. Proteins are converted to gas-phase, multiply-charged, positive ions by electrospray ionization and then allowed to react with fluoranthene radical anions. Electron transfer to the multiply charged protein promotes random fragmentation of amide bonds along the protein backbone. Multiply charged fragment ions are then deprotonated in a second ion/ion reaction with even-electron benzoate anions. M/z values for the resulting singly and doubly charged ions are used to read a sequence of 15-40 amino acids at both the N-terminus and the C-terminus of the protein. This information, along with the measured mass of the intact protein, are employed to identify known proteins and to detect the presence of post-translational modifications. In this study, we analyze intact proteins from the Escherchia coli 70S ribosomal protein complex and identify 46 of the 55 known unique components in a single, 90 min, on-line, chromatography experiment. Truncated versions of the above proteins along with several post-translational modifications are also detected. http://www.hubmed.org/display.cgi?uids=17364019 http://www.hubmed.org/display.cgi?uids=19337574 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=19337574">Int J Mass Spectrom</a>. 2007 Jan 1; 259(1-3): 105-116<br>Xia Q, Wang T, Park Y, Lamont RJ, Hackett M<p>Differential analysis of whole cell proteomes by mass spectrometry has largely been applied using various forms of stable isotope labeling. While metabolic stable isotope labeling has been the method of choice, it is often not possible to apply such an approach. Four different label free ways of calculating expression ratios in a classic "two-state" experiment are compared: signal intensity at the peptide level, signal intensity at the protein level, spectral counting at the peptide level, and spectral counting at the protein level. The quantitative data were mined from a dataset of 1245 qualitatively identified proteins, about 56% of the protein encoding open reading frames from Porphyromonas gingivalis, a Gram-negative intracellular pathogen being studied under extracellular and intracellular conditions. Two different control populations were compared against P. gingivalis internalized within a model human target cell line. The q-value statistic, a measure of false discovery rate previously applied to transcription microarrays, was applied to proteomics data. For spectral counting, the most logically consistent estimate of random error came from applying the locally weighted scatter plot smoothing procedure (LOWESS) to the most extreme ratios generated from a control technical replicate, thus setting upper and lower bounds for the region of experimentally observed random error. http://www.hubmed.org/display.cgi?uids=19337574 http://www.hubmed.org/display.cgi?uids=19079801 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=19079801">Int J Mass Spectrom</a>. 2007 Jan 1; 259(1-3): 87-95<br>Robinson EW, Sellon RE, Williams ER<p>Protonated poly(ethylene glycol), produced by electrospray ionization (ESI), with molecular weights ranging from 0.3 to 5 kDa and charge states from 1+ to 7+ were characterized using high-field asymmetric waveform ion mobility spectrometry (FAIMS). Results for all but some of the 3+ and 4+ charge states are consistent with a single gas-phase conformer or family of unresolved conformers for each of these charge states. The FAIMS compensation voltage scans resulted in peaks that could be accurately fit with a single Gaussian for each peak. The peak widths increase linearly with compensation voltage for maximum ion transmission but do not depend on m/z or molecular weight. Fitting parameters obtained from the poly(ethylene glycol) data were used to analyze conformations of oxidized and reduced lysozyme formed from different solutions. For oxidized lysozyme formed from a buffered aqueous solution, a single conformer (or group of unresolved conformers) was observed for the 7+ and 8+ charge states. Two conformers were observed for the 9+ and 10+ charge states formed from more denaturing solutions. Data for the fully reduced form indicate the existence of up to three different conformers for each charge state produced directly by ESI and a general progression from a more extended to a more folded structure with decreasing charge state. These results are consistent with those obtained previously by proton-transfer reactivity and drift tube ion mobility experiments, although more conformers were identified for the fully reduced form of lysozyme using FAIMS. http://www.hubmed.org/display.cgi?uids=19079801 http://www.hubmed.org/display.cgi?uids=19081753 <p><a rel="nofollow" target="_blank" href="http://www.hubmed.org/fulltext.cgi?uids=19081753">Int J Mass Spectrom</a>. 2006 Jul 1; 253(3): 256-262<br>Bush MF, Saykally RJ, Williams ER<p>Forming hydrated clusters containing triply charged metal ions is challenging due to the competing process of dissociation by forming the metal hydroxide with one less net charge and a protonated water molecule. It is demonstrated for the first time that it is possible to form such clusters using a method we call "nanodrop mass spectrometry". Clusters of the form [M(H(2)O)(n)](3+), where M = Ce, Eu, and La, are generated using electrospray ionization and are mass analyzed in a Fourier-transform ion cyclotron resonance mass spectrometer with an ion cell cooled to -140 degrees C. Clusters containing trivalent La with n ranging from 16 to over 160 can be readily produced. These clusters are stable at this temperature for many seconds, enabling all standard methods to probe structure and reactivity of these unusual species. Photodissociation experiments on extensively hydrated clusters of trivalent lanthanum using resonant infrared radiation indicate that a minimum of 17 water molecules is necessary to stabilize these trivalent clusters under the low-energy ion excitation conditions and long time frame of these experiments. These results indicate that a minimum droplet size of approximately a nanometer is necessary for these trivalent species to survive intact. This suggests that elemental speciation of trivalent metal ions from aqueous solutions should be possible using nanodrop mass spectrometry. http://www.hubmed.org/display.cgi?uids=19081753 http://dx.doi.org/10.1002%2Fmas.20272 Radiation metabolomics can be defined as the global profiling of biological fluids to uncover latent, endogenous small molecules whose concentrations change in a dose-response manner following exposure to ionizing radiation. In response to the potential threat of nuclear or radiological terrorism, the Center for High-Throughput Minimally Invasive Radiation Biodosimetry was established to develop field-deployable biodosimeters based, in part, on rapid analysis by mass spectrometry of readily and easily obtainable biofluids. In this review, we briefly summarize radiation biology and key events related to actual and potential nuclear disasters, discuss the important contributions the field of mass spectrometry has made to the field of radiation metabolomics, and summarize current discovery efforts to use mass spectrometry-based metabolomics to identify dose-responsive urinary constituents, and ultimately to build and deploy a noninvasive high-throughput biodosimeter. © 2009 Wiley Periodicals, Inc. Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_06d12791635c90b3a74dbdecc68b4e85 Wed, 04 Nov 2009 04:53:00 -0800 http://dx.doi.org/10.1002%2Fmas.20274 No Abstract wKB6qta72xGqBxWCkAtvUw_89dbff3a97b9062886f7896437ec4ded Wed, 04 Nov 2009 04:49:00 -0800 http://dx.doi.org/10.1002%2Fmas.20273 There are several basic characteristics of mass spectrometry that are not always fully appreciated by the science community. These characteristics include the distinction between relative and absolute isotope abundances, and the influence of isotope fractionation on the accuracy of isotopic measurements. These characteristics can be illustrated in the field of nuclear physics with reference to the measurement of nuclear parameters, which involve the use of enriched isotopes, and to test models of s-, r-, and p-process nucleosynthesis. The power of isotope-dilution mass spectrometry (IDMS) to measure trace elements in primitive meteorites to produce accurate Solar System abundances has been essential to the development of nuclear astrophysics. The variety of mass spectrometric instrumentation used to measure the isotopic composition of elements has sometimes been accompanied by a lack of implementation of basic mass spectrometric protocols which are applicable to all instruments. These metrological protocols are especially important in atomic weight determinations, but must also be carefully observed in cases where the anomalies might be very small, such as in studies of the daughter products of extinct radionuclides to decipher events in the early history of the Solar System. There are occasions in which misleading conclusions have been drawn from isotopic data derived from mass spectrometers where such protocols have been ignored. It is important to choose the mass spectrometer instrument most appropriate to the proposed experiment. The importance of the integrative nature of mass spectrometric measurements has been demonstrated by experiments in which long, double beta decay and geochronological decay half-lives have been measured as an alternative to costly radioactive-counting experiments. This characteristic is also illustrated in the measurement of spontaneous fission yields, which have accumulated over long periods of time. Mass spectrometry is also a valuable tool in the determination of neutron capture cross-section measurements and the application of such determinations in Planetary Science. © 2009 Wiley Periodicals, Inc. Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_453c5106b6e527bf76058f7cf62d7d80 Thu, 29 Oct 2009 08:28:00 -0700 http://dx.doi.org/10.1002%2Fmas.20267 This review discusses recent emerging techniques that have been used to couple flow-injection analysis (FIA) and electrospray ionization-mass spectrometry (ESI-MS) for the quantitation of noncovalent binding interactions. Focus is placed predominantly on two such methods. Diffusion-based measurements, developed by Konermann and co-workers, uses controlled-band dispersion prior to ESI-MS to determine diffusion constants and binding constants based on the temporal variation of ligand signal measured in the mass spectrum (an indirect technique). Dynamic titration, developed by Schug and co-workers, is a direct method, where a temporal compositional gradient of a guest molecule is induced in the presence of host in solution to monitor the concentration dependence of complex formation as a function of observed complex ion abundance after ESI-MS. Further discussion places these techniques in the context of a variety of other direct and indirect ESI-MS-based binding determination methods, and highlights advantages, disadvantages, and practical considerations for their proper use to investigate a broad range of macromolecular and small-molecule interaction systems. © 2009 Wiley Periodicals, Inc. Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_8f5c96095d1e277bb5ef7f7905cb9aca Wed, 04 Nov 2009 05:10:00 -0800 http://dx.doi.org/10.1002%2Fmas.20259 This review of mass spectrometry of sulfonylurea herbicides includes a focus on studies relevant to Canadian Prairie waters. Emphasis is given to data gaps in the literature for the rates of photolysis of selected sulfonylurea herbicides in different water matrices. Specifically, results are evaluated for positive ion electrospray tandem mass spectrometry with liquid chromatography separation for the study of the photolysis of chlorsulfuron, tribenuron-methyl, thifensulfuron-methyl, metsulfuron-methyl, and ethametsulfuron-methyl. LC-MS/MS is shown to be the method of choice for the quantification of sulfonylurea herbicides with instrumental detection limits ranging from 1.3 to 7.2 pg (on-column). Tandem mass spectrometry coupled with the use of authentic standards likewise has proven to be well suited for the identification of transformation products. To date, however, the power of time-of-flight MS and ultrahigh resolution MS has not been exploited fully for the identification of unknown photolysis products. Dissipation of the herbicides under natural sunlight fit pseudo-first-order kinetics with half-life values ranging from 4.4 to 99 days. For simulated sunlight, radiation wavelengths shorter than 400 nm are required to induce significant photolytic reactions. The correlation between field dissipation studies and laboratory photolysis experiments suggests that photolysis is a major pathway for the dissipation of some sulfonylurea herbicides in natural Prairie waters. © 2009 Wiley Periodicals, Inc. Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_6247fbaf512140abb3300b5a0d9c0deb Wed, 04 Nov 2009 04:58:00 -0800 http://dx.doi.org/10.1002%2Fmas.20261 The concept of a dynamic state of body constituents, a precursor of the modern term of proteome dynamics, was conceived over a century ago. But, not until recently can we examine the dynamics of individual "constituents" for example, proteins at a truly global level. The path of advancement in our understanding of protein turnover at the global level is marked by the introduction of some key technological innovations. These methods include the isotopic tracer technique in the 1930s, the two-dimensional gel electrophoresis technique in the 1970s, the sector mass spectrometer that could analyze isotopomers of peptides in the early 1990s, the 2D gel/MALDI-TOF proteomics technology in the late 1990s, the booming liquid chromatography/mass spectrometry proteomics technology in this decade, and the recently emerging protein-tagging approaches that offer single-cell resolution for protein turnover measurements. The long-standing inquiry raised in the 1950s about the existence of a dynamic state in different organisms at different physiological conditions can now be answered with an individual "constituent" resolution on a truly global scale. Now it appears that protein degradation is not necessarily an end to the protein function. Rather, it can be the start of a new function because protein degradation clears the way for the action of other proteins. Protein turnover participates in a multi-layer complex regulatory network and shares equal importance with gene transcription and protein translation. The advances in technologies for protein turnover analysis and the improved understanding of the biological role of protein turnover will likely help to solve some long-standing biomedical problems such as the tuberculosis disease that at the present day still affects one-third of the world population. © 2009 Wiley Periodicals, Inc. Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_591265ead9b8d1ac1cd213808fe287ea Tue, 15 Sep 2009 08:17:00 -0700 http://dx.doi.org/10.1002%2Fmas.20257 This article reviews the numerous ways in which inductively coupled plasma mass spectrometry has been used for the analysis of environmental samples since it was commercially introduced in 1983. Its multielemental isotopic capability, high sensitivity and wide linear dynamic range makes it ideally suited for environmental analysis. Provided that some care is taken during sample preparation and that appropriate calibration strategies are used to circumvent non-spectroscopic interferences, the technique is readily applicable to the analysis of a wide variety of environmental samples (natural waters, soils, rocks, sediments, vegetation, etc.), using quadrupole, time-of-flight or double-focusing sector-field mass spectrometers. In cases where spectroscopic interferences arising from the sample matrix cannot be resolved, then separation methods can be implemented either on- or off-line, which can simultaneously allow analyte preconcentration, thus further decreasing the already low detection limits that are achievable. In most cases, the blank, prepared by following the same steps as for the sample but without the sample, limits the ultimate detection limits that can be reached. © 2009 Wiley Periodicals, Inc. Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_5c612b4c6e44b21c6ff7e373a0e02ecf Mon, 31 Aug 2009 07:21:00 -0700 http://dx.doi.org/10.1002%2Fmas.20263 This review summarized the applications of mass spectrometric techniques for the analysis of the important flame retardants polybrominated diphenyl ethers (PBDEs) to understand the environmental sources, fate and toxicity of PBDEs that were briefly discussed to give a general idea for the need of analytical methodologies. Specific performance of various mass spectrometers hyphenated with, for example, gas chromatograph, liquid chromatograph, and inductively coupled plasma (GC/MS, LC/MS, and ICP/MS, respectively) for the analysis of PBDEs was compared with an objective to present the information on the evolution of MS techniques for determining PBDEs in environmental and human samples. GC/electron capture negative ionization quadrupole MS (GC/NCI qMS), GC/high resolution MS (GC/HRMS) and GC ion trap MS (GC/ITMS) are most commonly used MS techniques for the determination of PBDEs. New analytical technologies such as fast tandem GC/MS and LC/MS become available to improve analyses of higher PBDEs. The development and application of the tandem MS techniques have helped to understand environmental fate and transformations of PBDEs of which abiotic and biotic degradation of decaBDE is thought to be one major source of Br1-9BDEs present in the environment in addition to direct loading from commercial mixtures. MS-based proteomics will offer an insight into the molecular mechanisms of toxicity and potential developmental and neurotoxicity of PBDEs. © 2009 Wiley Periodicals, Inc. Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_fc38f9f91ba79df7232378768936f615 Mon, 31 Aug 2009 07:10:00 -0700 http://dx.doi.org/10.1002%2Fmas.20264 Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been recognized as a primary methodology for the accurate analysis of endogenous steroid hormones in biological samples. This review focuses on the use of LC-MS/MS in clinical laboratories to assist with the diagnosis of diverse groups of endocrine and metabolic diseases. Described analytical methods use on-line and off-line sample preparation and analytical derivatization to enhance analytical sensitivity, specificity, and clinical utility. Advantages of LC-MS/MS as an analytical technique include high specificity, possibility to simultaneously measure multiple analytes, and the ability to assess the specificity of the analysis in every sample. All described analytical methods were extensively validated, utilized in routine diagnostic practice, and were applied in a number of clinical and epidemiological studies, including a study of the steroidogenesis in ovarian follicles. © 2009 Wiley Periodicals, Inc. Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_68bc63b500b3563ca4ef64711cd15380 Tue, 25 Aug 2009 00:55:00 -0700 http://dx.doi.org/10.1002%2Fmas.20262 No Abstract. wKB6qta72xGqBxWCkAtvUw_985a8896036a5d4f24ddc1346104509e Tue, 25 Aug 2009 00:45:00 -0700 http://dx.doi.org/10.1002%2Fmas.20255 The analysis of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, polychlorinated biphenyls, and other related compounds requires complex sample preparation and analytical procedures using highly sensitive and selective state-of-the-art instrumentation to meet very stringent data quality objectives. The analytical procedures (extraction, sample preparation), instrumentation (chromatographic separation and detection by mass spectrometry) and screening techniques for the determination of dioxins, furans, dioxin-like polychlorinated biphenyls and related compounds with a focus on new approaches and alternate techniques to standard regulatory methods are reviewed. © 2009 Wiley Periodicals, Inc. Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_60dd95e3e30755a164d9cd8b4ec32804 Tue, 11 Aug 2009 05:24:00 -0700 http://dx.doi.org/10.1002%2Fmas.20256 This review discusses various mass spectrometry (MS)-based approaches for exploring structural aspects of proteins in solution. Electrospray ionization (ESI)-MS, in particular, has found fascinating applications in this area. For example, when used in conjunction with solution-phase hydrogen/deuterium exchange (HDX), ESI-MS is a highly sensitive tool for probing conformational dynamics. The main focus of this article is a technique that is complementary to HDX, that is, the covalent labeling of proteins by hydroxyl radicals. The reactivity of individual amino acid side chains with .OH is strongly affected by their degree of solvent exposure. Thus, analysis of the oxidative labeling pattern by peptide mapping and tandem mass spectrometry provides detailed structural information. A convenient method for .OH production is the photolysis of H2O2 by a pulsed UV laser, resulting in oxidative labeling on the microsecond time scale. Selected examples demonstrate the use of this technique for structural studies on membrane proteins, and the combination with rapid mixing devices for characterizing the properties of short-lived protein (un)folding intermediates. © 2009 Wiley Periodicals, Inc. Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_228e61d9017ec7a6802795040c8fd58d Tue, 11 Aug 2009 05:32:00 -0700 http://dx.doi.org/10.1002%2Fmas.20253 Glycosphingolipids (GSLs), composed of a hydrophilic carbohydrate chain and a lipophilic ceramide anchor, play pivotal roles in countless biological processes, including infectious diseases and the development of cancer. Knowledge of the number and sequence of monosaccharides and their anomeric configuration and linkage type, which make up the principal items of the glyco code of biologically active carbohydrate chains, is essential for exploring the function of GSLs. As part of the investigation of the vertebrate glycome, GSL analysis is undergoing rapid expansion owing to the application of novel biochemical and biophysical technologies. Mass spectrometry (MS) takes part in the network of collaborations to further unravel structural and functional aspects within the fascinating world of GSLs with the ultimate aim to better define their role in human health and disease. However, a single-method analytical MS technique without supporting tools is limited yielding only partial structural information. Because of its superior resolving power, robustness, and easy handling, high-performance thin-layer chromatography (TLC) is widely used as an invaluable tool in GSL analysis. The intention of this review is to give an insight into current advances obtained by coupling supplementary techniques such as TLC and mass spectrometry. A retrospective view of the development of this concept and the recent improvements by merging (1) TLC separation of GSLs, (2) their detection with oligosaccharide-specific proteins, and (3) in situ MS analysis of protein-detected GSLs directly on the TLC plate, are provided. The procedure works on a nanogram scale and was successfully applied to the identification of cancer-associated GSLs in several types of human tumors. The combination of these two supplementary techniques opens new doors by delivering specific structural information of trace quantities of GSLs with only limited investment in sample preparation. © 2009 Wiley Periodicals, Inc. Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_a6a16bbbc2e6fd18126bb79193ef12c8 Thu, 16 Jul 2009 07:53:00 -0700 http://dx.doi.org/10.1002%2Fmas.20243 The brain is unquestionably the most fascinating organ, and the hippocampus is crucial in memory storage and retrieval and plays an important role in stress response. In temporal lobe epilepsy (TLE), the seizure origin typically involves the hippocampal formation. Despite tremendous progress, current knowledge falls short of being able to explain its function. An emerging approach toward an improved understanding of the complex molecular mechanisms that underlie functions of the brain and hippocampus is neuroproteomics. Mass spectrometry has been widely used to analyze biological samples, and has evolved into an indispensable tool for proteomics research. In this review, we present a general overview of the application of mass spectrometry in proteomics, summarize neuroproteomics and systems biology-based discovery of protein biomarkers for epilepsy, discuss the methodology needed to explore the epileptic hippocampus proteome, and also focus on applications of ingenuity pathway analysis (IPA) in disease research. This neuroproteomics survey presents a framework for large-scale protein research in epilepsy that can be applied for immediate epileptic biomarker discovery and the far-reaching systems biology understanding of the protein regulatory networks. Ultimately, knowledge attained through neuroproteomics could lead to clinical diagnostics and therapeutics to lessen the burden of epilepsy on society. © 2009 Wiley Periodicals, Inc., Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_0dd44fd756d71c6730debda8449a2b46 Mon, 13 Jul 2009 06:44:00 -0700 http://dx.doi.org/10.1002%2Fmas.20239 The distribution analysis of (essential, beneficial, or toxic) metals (e.g., Cu, Fe, Zn, Pb, and others), metalloids, and non-metals in biological tissues is of key interest in life science. Over the past few years, the development and application of several imaging mass spectrometric techniques has been rapidly growing in biology and medicine. Especially, in brain research metalloproteins are in the focus of targeted therapy approaches of neurodegenerative diseases such as Alzheimer's and Parkinson's disease, or stroke, or tumor growth. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) using double-focusing sector field (LA-ICP-SFMS) or quadrupole-based mass spectrometers (LA-ICP-QMS) has been successfully applied as a powerful imaging (mapping) technique to produce quantitative images of detailed regionally specific element distributions in thin tissue sections of human or rodent brain. Imaging LA-ICP-QMS was also applied to investigate metal distributions in plant and animal sections to study, for example, the uptake and transport of nutrient and toxic elements or environmental contamination. The combination of imaging LA-ICP-MS of metals with proteomic studies using biomolecular mass spectrometry identifies metal-containing proteins and also phosphoproteins. Metal-containing proteins were imaged in a two-dimensional gel after electrophoretic separation of proteins (SDS or Blue Native PAGE). Recent progress in LA-ICP-MS imaging as a stand-alone technique and in combination with MALDI/ESI-MS for selected life science applications is summarized. © 2009 Wiley Periodicals, Inc., Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_41182148a9e33289fb20c3ad10ce9fd6 Thu, 25 Jun 2009 08:06:00 -0700 http://dx.doi.org/10.1002%2Fmas.20252 Hydrophilic interaction liquid chromatography (HILIC), although not a new technique, has enjoyed a recent renaissance with the introduction of robust and reproducible stationary phases. It is consequently finding application in metabolomics studies, which have traditionally relied on the stability of reversed phases (RPs), since the biofluids analyzed are predominantly aqueous and thus contain many polar analytes. HILIC's retention of those polar compounds and use of solvents readily compatible with mass spectrometry have seen its increasing adoption in studies of complex aqueous metabolomes. This review describes the stationary phases and their features, surveys HILIC-LC-MS's role in metabolomics experiments, discusses approaches to data extraction and analysis including multivariate analysis, and reviews the literature on HILIC-MS applications in metabolomics. © 2009 Wiley Periodicals, Inc., Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_eaeb9a5de970baf6baa81d0bf06b6c30 Thu, 25 Jun 2009 08:09:00 -0700 http://dx.doi.org/10.1002%2Fmas.20238 Microfabrication of analytical devices is currently of growing interest and many microfabricated instruments have also entered the field of mass spectrometry (MS). Various (atmospheric pressure) ion sources as well as mass analyzers have been developed exploiting microfabrication techniques. The most common approach thus far has been the miniaturization of the electrospray ion source and its integration with various separation and sampling units. Other ionization techniques, mainly atmospheric pressure chemical ionization and photoionization, have also been subject to miniaturization, though they have not attracted as much attention. Likewise, all common types of mass analyzers have been realized by microfabrication and, in most cases, successfully applied to MS analysis in conjunction with on-chip ionization. This review summarizes the latest achievements in the field of microfabricated ion sources and mass analyzers. Representative applications are reviewed focusing on the development of fully microfabricated systems where ion sources or analyzers are integrated with microfluidic separation devices or microfabricated pums and detectors, respectively. Also the main microfabrication methods, with their possibilities and constraints, are briefly discussed together with the most commonly used materials. © 2009 Wiley Periodicals, Inc., Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_d70668c22d7a81a9fbb7047d1db55f20 Tue, 09 Jun 2009 09:48:00 -0700 http://dx.doi.org/10.1002%2Fmas.20244 The variations in the isotopic composition of calcium caused by fractionation in heterogeneous systems and by nuclear reactions can provide insight into numerous biological, geological, and cosmic processes, and therefore isotopic analysis finds a wide spectrum of applications in cosmo- and geochemistry, paleoclimatic, nutritional, and biomedical studies. The measurement of calcium isotopic abundances in natural samples has challenged the analysts for more than three decades. Practically all Ca isotopes suffer from significant isobaric interferences, whereas low-abundant isotopes can be particularly affected by neighboring major isotopes. The extent of natural variations of stable isotopes appears to be relatively limited, and highly precise techniques are required to resolve isotopic effects. Isotope fractionation during sample preparation and measurements and instrumental mass bias can significantly exceed small isotope abundance variations in samples, which have to be investigated. Not surprisingly, a TIMS procedure developed by Russell et al. (Russell et al., . Geochim Cosmochim Acta 42: 1075-1090) for Ca isotope measurements was considered as revolutionary for isotopic measurements in general, and that approach is used nowadays (with small modifications) for practically all isotopic systems and with different mass spectrometric techniques. Nevertheless, despite several decades of calcium research and corresponding development of mass spectrometers, the available precision and accuracy is still not always sufficient to achieve the challenging goals. The present article discusses figures of merits of presently used analytical methods and instrumentation, and attempts to critically assess their limitations. In Sections 2 and 3, mass spectrometric methods applied to precise stable isotope analysis and to the determination of 41Ca are described. Section 4 contains a short summary of selected applications, and includes tracer experiments and the potential use of biological isotope fractionation in medical studies, paleoclimatic and paleoceanographic, and other terrestrial as well as extraterrestrial investigations. © 2009 Wiley Periodicals, Inc., Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_20d78893d61a7e3856445fb307d382c8 Tue, 23 Jun 2009 01:50:00 -0700 http://dx.doi.org/10.1002%2Fmas.20241 In the post-genomics era, proteomics has become a central branch in life sciences. An understanding of biological functions will not only rely on protein identification, but also on protein quantification in a living organism. Most of the existing methods for quantitative proteomics are based on isotope labeling combined with molecular mass spectrometry. Recently, a remarkable progress that utilizes inductively coupled plasma-mass spectrometry (ICP-MS) as an attractive complement to electrospray MS and MALDI MS for protein quantification, especially for absolute quantification, has been achieved. This review will selectively discuss the recent advances of ICP-MS-based technique, which will be expected to further mature and to become one of the key methods in quantitative proteomics. © 2009 Wiley Periodicals, Inc. Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_86fde51c9064676181fae1439015401c Tue, 02 Jun 2009 00:41:00 -0700 http://dx.doi.org/10.1002%2Fmas.20233 Cluster secondary ion mass spectrometry (cluster SIMS) has played a critical role in the characterization of polymeric materials over the last decade, allowing for the ability to obtain spatially resolved surface and in-depth molecular information from many polymer systems. With the advent of new molecular sources such as , , , and , there are considerable increases in secondary ion signal as compared to more conventional atomic beams (Ar+, Cs+, or Ga+). In addition, compositional depth profiling in organic and polymeric systems is now feasible, without the rapid signal decay that is typically observed under atomic bombardment. The premise behind the success of cluster SIMS is that compared to atomic beams, polyatomic beams tend to cause surface-localized damage with rapid sputter removal rates, resulting in a system at equilibrium, where the damage created is rapidly removed before it can accumulate. Though this may be partly true, there are actually much more complex chemistries occurring under polyatomic bombardment of organic and polymeric materials, which need to be considered and discussed to better understand and define the important parameters for successful depth profiling. The following presents a review of the current literature on polymer analysis using cluster beams. This review will focus on the surface and in-depth characterization of polymer samples with cluster sources, but will also discuss the characterization of other relevant organic materials, and basic polymer radiation chemistry. © 2009 Wiley Periodicals, Inc., Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_76c901c92bf85d0afe621e4cd11e7701 Fri, 15 May 2009 01:25:00 -0700 http://dx.doi.org/10.1002%2Fmas.20237 The photoneuroendocrine circadian system of the brain consists of (a) specialized photoreceptors in the retina, (b) a circadian generator located in the forebrain that contains "clock genes," (c) specialized nuclei in the forebrain involved in neuroendocrine secretion, and (d) the pineal gland. The circadian generator is a nucleus, called the suprachiasmatic nucleus (SCN). The neurons of this nucleus contain "clock genes," the transcription of which exhibits a circadian rhythm. Most circadian rhythms are generated by the neurons of this nucleus and, via neuronal and humoral connections, the SCN controls circadian activity of the brain and peripheral tissues. The endogenous oscillator of the SCN is each day entrained to the length of the daily photoperiod by light that reach the retina, and specialized photoreceptors transmit impulses to the SCN via the optic nerves. Mass screening for day/night variations in gene expression in the circadian system as well as in the whole brain and peripheral tissues have, during the last decade, been performed. However, studies of circadian changes in the proteome have been less investigated. In this survey, the anatomy and function of the circadian-generating system in mammals is described, and recent proteomic studies that investigate day/night changes in the retina, SCN, and pineal gland are reviewed. Further circadian changes controlled by the SCN in gene and protein expression in the liver are discussed. © 2009 Wiley Periodicals, Inc. Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_a971c36b896c2e73c3efdc231232bb15 Tue, 12 May 2009 09:00:00 -0700 http://dx.doi.org/10.1002%2Fmas.20240 The roles of metal ions to sustain normal function and to cause dysfunction of neurological systems have been confirmed by various studies. However, because of the lack of adequate analytical method to monitor the transfer kinetics of metal ions in the brain of a living animal, research on the physiopathological roles of metal ions in the CNS remains in its early stages and more analytical efforts are still needed. To explicitly model the possible links between metal ions and physiopathological alterations, it is essential to develop in vivo monitoring techniques that can bridge the gap between metalloneurochemistry and neurophysiopathology. Although inductively coupled plasma mass spectrometry (ICP-MS) is a very powerful technique for multiple trace element analyses, when dealing with chemically complex microdialysis samples, the detection capability is largely limited by instrumental sensitivity, selectivity, and contamination that arise from the experimental procedure. As a result, in recent years several high efficient and clean on-line sample pretreatment systems have been developed and combined with microdialysis and ICP-MS for the continuous and in vivo determination of the concentration-time profiles of metal ions in the extracellular space of rat brain. This article reviews the research relevant to the development of analytical techniques for the in vivo determination of dynamic variation in the concentration levels of metal ions in a living animal. © 2009 Wiley Periodicals, Inc. Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_55ab20f34a4bf054ed3764c804b0bb9d Tue, 12 May 2009 09:04:00 -0700 http://dx.doi.org/10.1002%2Fmas.20232 The electrodynamic ion funnel has enabled the manipulation and focusing of ions in a pressure regime (0.1-30 Torr) that has challenged traditional approaches, and provided the basis for much greater mass spectrometer ion transmission efficiencies. The initial ion funnel implementations aimed to efficiently capture ions in the expanding gas jet of an electrospray ionization interface and radially focus them for efficient transfer through a conductance limiting orifice. We review the improvements in fundamental understanding of ion motion in ion funnels, the evolution in its implementations that have brought the ion funnel to its current state of refinement, as well as applications of the ion funnel for purposes such as ion trapping, ion cooling, low pressure electrospray, and ion mobility spectrometry. © 2009 Wiley Periodicals, Inc., Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_46daee56cb5f1da0696a37bddbefa1f6 Thu, 23 Apr 2009 04:19:00 -0700 http://dx.doi.org/10.1002%2Fmas.20234 This article reviews recent literature on current methodologies based on chromatography coupled to mass spectrometry to analyze phenolic compounds with endocrine-disrupting capabilities. For this review we chose alkylphenol ethoxylates, bisphenol A, bisphenol F, and their degradation products and halogenated derivatives, which are considered important environmental contaminants. Additionally, some related compounds such as bisphenol diglycidylethers were included. Growing attention has been paid to the mass spectrometric characterization of these compounds and the instrumentation and strategies used for their quantification and confirmation. The current use of gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) methodologies with different mass spectrometers and ionization and monitoring modes is discussed. Practical aspects with regards to the use of these analytical techniques, such as derivatizing reagents in GC-MS, ion suppression in LC-MS, and the most problematic aspects of quantification, are included in the discussion. © 2009 Wiley Periodicals, Inc., Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_2773a91de03e4fa0497dbf3a3cc4fd61 Tue, 14 Apr 2009 08:00:00 -0700 http://dx.doi.org/10.1002%2Fmas.20221 Protein glycosylation regulates protein function and cellular distribution. Additionally, aberrant protein glycosylations have been recognized to play major roles in human disorders, including neurodegenerative diseases. Glycoproteomics, a branch of proteomics that catalogs and quantifies glycoproteins, provides a powerful means to systematically profile the glycopeptides or glycoproteins of a complex mixture that are highly enriched in body fluids, and therefore, carry great potential to be diagnostic and/or prognostic markers. Application of this mass spectrometry-based technology to the study of neurodegenerative disorders (e.g., Alzheimer's disease and Parkinson's disease) is relatively new, and is expected to provide insight into the biochemical pathogenesis of neurodegeneration, as well as biomarker discovery. In this review, we have summarized the current understanding of glycoproteins in biology and neurodegenerative disease, and have discussed existing proteomic technologies that are utilized to characterize glycoproteins. Some of the ongoing studies, where glycoproteins isolated from cerebrospinal fluid and human brain are being characterized in Parkinson's disease at different stages versus controls, are presented, along with future applications of targeted validation of brain specific glycoproteins in body fluids. © 2009 Wiley Periodicals, Inc., Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_4b75d54f86f27b1abd531b4e05c8376d Wed, 08 Apr 2009 03:25:00 -0700 http://dx.doi.org/10.1002%2Fmas.20235 Natural products, and their derivatives and mimics, have contributed to the development of important therapeutics to combat diseases such as infections and cancers over the past decades. The value of natural products to modern drug discovery is still considerable. However, its development is hampered by a lack of a mechanistic understanding of their molecular action, as opposed to the emerging molecule-targeted therapeutics that are tailored to a specific protein target(s). Recent advances in the mass spectrometry-based proteomic approaches have the potential to offer unprecedented insights into the molecular action of natural products. Chemical proteomics is established as an invaluable tool for the identification of protein targets of natural products. Small-molecule affinity selection combined with mass spectrometry is a successful strategy to "fish" cellular targets from the entire proteome. Mass spectrometry-based profiling of protein expression is also routinely employed to elucidate molecular pathways involved in the therapeutic and possible toxicological responses upon treatment with natural products. In addition, mass spectrometry is increasingly utilized to probe structural aspects of natural products-protein interactions. Limited proteolysis, photoaffinity labeling, and hydrogen/deuterium exchange in conjunction with mass spectrometry are sensitive and high-throughput strategies that provide low-resolution structural information of non-covalent natural product-protein complexes. In this review, we provide an overview on the applications of mass spectrometry-based techniques in the identification and characterization of natural product-protein interactions, and we describe how these applications might revolutionize natural product-based drug discovery. © 2009 Wiley Periodicals, Inc., Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_7a1aed0eef2ffa4f97dc81164c7773b2 Tue, 24 Mar 2009 03:11:00 -0700 http://dx.doi.org/10.1002%2Fmas.20226 Oxidative stress has been implicated in the pathogenesis of numerous human diseases and disorders, but the mechanistic basis often remains enigmatic. The Sod2 mutant mouse, which is sensitized to mitochondrial stress, is an ideal mutant model for studying the role of oxidative stress in a diverse range of complications arising from mitochondrial dysfunction and diminished antioxidant defense. To fully appreciate the widespread molecular consequences under increased oxidative stress, a systems approach utilizing proteomics is able to provide a global overview of the complex biological changes, which a targeted single biomolecular approach cannot address fully. This review focuses on the applications of mass spectrometry and functional proteomics in the Sod2 mouse. The combinatorial approach provides novel insights into the interplay of chemistry and biology, free radicals and proteins, thereby augmenting our understanding of how redox perturbations influence protein dynamics. Ultimately, this knowledge can lead to the development of free radical-targeted therapies. © 2009 Wiley Periodicals, Inc., Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_9721d450b506ec2c990c34b634681195 Tue, 17 Mar 2009 07:29:00 -0700 http://dx.doi.org/10.1002%2Fmas.20219 Mass spectrometry is the tool of choice to investigate protein phosphorylation, which plays a vital role in cell regulation and diseases such as cancer. However, low abundances of phosphopeptides and low degrees of phosphorylation typically necessitate isolation and concentration of phosphopeptides prior to MS analysis. This review discusses the enrichment of phosphopeptides with immobilized metal affinity chromatography, reversible covalent binding, and metal oxide affinity chromatography. Capture of phosphopeptides on TiO2 seems especially promising in terms of selectivity and recovery, but the success of all methods depends on careful selection of binding, washing, and elution solutions. Enrichment techniques are complementary, such that a combination of methods greatly enhances the number of phosphopeptides isolated from complex samples. Development of a standard series of phosphopeptides in a highly complex mixture of digested proteins would greatly aid the comparison of different enrichment methods. Phosphopeptide binding to magnetic beads and on-plate isolation prior to MALDI-MS are emerging as convenient methods for purification of small (µL) samples. On-plate enrichment can yield &gt;70% recoveries of phosphopeptides in mixtures of a few digested proteins and can avoid sample-handling steps, but this technique is likely limited to relatively simple samples such as immunoprecipitates. With recent advances in enrichment techniques in hand, MS analysis should provide important insights into phosphorylation pathways. © 2009 Wiley Periodicals, Inc., Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_6e9c323a1d847992ccf0a62be09ef4ad Wed, 04 Mar 2009 06:20:00 -0800 http://dx.doi.org/10.1002%2Fmas.20220 Laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) is a solid sampling technique in continuous expansion in all types of research fields in which direct multi-elemental or isotopic analysis is required. In particular, this technique shows unique characteristics that made its use recommended in many archaeometric applications, where valuable solid artifacts are often the target samples, because it offers flexibility to achieve spatially resolved information with high detection power and a wide linear range, in a fast and straightforward way, and with minimal sample damage. The current review provides a systematic survey of publications that reported the use of LA-ICPMS in an archaeological context, highlights its main capabilities and limitations and discusses the most relevant parameters that influence the performance of this technique for this type of application. © 2009 Wiley Periodicals, Inc., Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_806577099f71797f7ea678bd76eb0727 Tue, 24 Feb 2009 06:02:00 -0800 http://dx.doi.org/10.1002%2Fmas.20212 Flavonoids are secondary plant metabolites of great structural variety and high medicinal significance. The search for new chemical entities and the quality control of flavonoid containing natural products require easy-to-use but reliable and robust analytical methodologies. For structural elucidation of flavonoids and their glycosides, nuclear magnetic resonance (NMR) and mass spectroscopy (MS) are the generally used techniques. In phytochemical analyses, however, high amounts of flavonoids are difficult to isolate for NMR, thus low sample volume requiring MS based methods are emerging. This review summarizes and compares currently available methods for structural elucidation of flavonoids by LC-MS and LC-MSn, and focuses on the identification options of unknown flavonoid glycosides in complex samples (e.g., plant extracts) with the emphasis on the differentiation of isomeric compounds. © 2008 Wiley Periodicals, Inc., Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_71bd1a252d90220073ebcf5d54da0466 Tue, 30 Dec 2008 01:58:00 -0800 http://dx.doi.org/10.1002%2Fmas.20213 Mass spectrometry has become the gold standard for the identification of proteins in proteomics. In this review, I will discuss the available literature on proteomic experiments that analyze human cerebrospinal fluid (CSF) and brain extracellular fluid (ECF), mostly obtained by cerebral microdialysis. Both materials are of high diagnostic value in clinical neurology, for example, in cerebrovascular disorders like stroke, neurodegenerative diseases like Alzheimer's Disease, Parkinson's Disease, amyotrophic lateral sclerosis (ALS), traumatic brain injury and cerebral infectious and inflammatory disease, such as multiple sclerosis. Moreover, there are standard procedures for sampling. In a number of studies in recent years, biomarkers have been proposed in CSF and ECF for improved diagnosis or to control therapy, based on proteomics and mass spectrometry. I will also discuss the needs for a transition of research-based experimental screening with mass spectrometry to fast and reliable diagnostic instrumentation for clinical use. © 2008 Wiley Periodicals, Inc., Mass Spec Rev wKB6qta72xGqBxWCkAtvUw_f569ccf2414e6cb305562814a1c6548b Tue, 30 Dec 2008 02:02:00 -0800 http://dx.doi.org/10.1002%2Fjms.1696 The present study was initiated to define the composition of the membrane proteome of the Natural Killer (NK) like cell line YTS. Isolated membranes were treated with reagents that have been reported to remove peripheral membrane proteins. Additional steps involving trifluoroethanol (TFE) were introduced in an effort to remove remaining nonintegral membrane proteins. This treatment resulted in the release of a subset of proteins without any apparent disruption of membrane integrity. The membranes were solubilized and digested with trypsin in 25% TFE. The resulting peptides were separated using an off-line two-dimensional reversed phase LC technique at alkaline and acidic pHs. Mass spectrometric analysis identified 1843 proteins with high confidence scores. On the basis of the presence of transmembrane regions or evidence of posttranslational modifications and prediction algorithms, approximately 40% of the identified proteins were predicted as plausible membrane proteins. The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes. The analytical approaches presented in this study offer robust generic methods for the identification and characterization of membrane proteins. These observations highlight the fact that the membrane is a dynamic entity that is composed of integral and stably associated proteins. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_62b7917802ca524d8dcdd1e6ca9ba6e4 Fri, 27 Nov 2009 01:34:00 -0800 http://dx.doi.org/10.1002%2Fjms.1694 A simple and sensitive liquid chromatography tandem multiple-stage mass spectrometry (HPLC/MS/MS) method suitable for bulk lisinopril analysis was developed, by which lisinopril and its RSS isomer were separated and differentiated. In the collision-induced dissociation (CID) mass spectra of the [M + H]+ ions, the abundance of the fragment ion of m/z 246 for lisinopril was about two times higher than the ion of m/z 245; however, the former fragment ion was noted to be a little lower than the latter for RSS isomer at all collision energies. In the CID mass spectra of the [M + Li]+ ion, the abundance of the rearrangement ion of m/z 315 for the RSS isomer was about three times higher than that for lisinopril. Furthermore, the difference was supported by the results of energy-resolved mass spectrometry (ERMS) in the test range of collision energies. Similar differences were also observed between the CID mass spectra of lisinopril and RSS isomer methylester, which indicated that the RSS isomer could be rapidly characterized by the CID mass spectra of both the protonated and lithium adduct ion. Elemental compositions of all the ions were confirmed by Fourier Transform ion cyclotron resonance ESI mass spectrometry (FT-ICR-ESI/MS). In addition, theoretical computations were carried out to support the experimental results. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_ef41bb556ed1f24c515874dac8b85fc3 Fri, 27 Nov 2009 01:34:00 -0800 http://dx.doi.org/10.1002%2Fjms.1704 Differentiation of [beta]-amino acid enantiomers with two chiral centres was investigated by kinetic method with trimeric metal-bound complexes. Four enantiomeric pairs of [beta]-amino acids were studied: cis-(1R,2S)-, cis-(1S,2R)-, trans-(1R,2R)- and trans-(1S,2S)-2-aminocyclopentanecarboxylic acids (cyclopentane [beta]-amino acids), and cis-(1R,2S)-, cis-(1S,2R)-, trans-(1R,2R)-, and trans-(1S,2S)-2-aminocyclohexanecarboxylic acids (cyclohexane [beta]-amino acids). The results showed that the choice of metal ion (Cu2+, Ni2+) and chiral reference compound ([alpha]- and [beta]-amino acids) had an effect on the enantioselectivity. Especially, aromaticity of the reference compound was noted to enhance the enantioselectivity. The fixed-ligand kinetic method, a modification of the kinetic method, was then applied to the same [beta]-amino acids, with dipeptides used as fixed ligands. With this method, dipeptide containing an aromatic side chain enhanced the enantioselectivity. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_42e86a60644c1054d4e29bf2fc1bff67 Wed, 25 Nov 2009 21:41:00 -0800 http://dx.doi.org/10.1002%2Fjms.1703 N-Hydroxylated polyamine derivatives were found to decompose during the ionization process of liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) experiments. The phenomenon was studied with a model compound, a synthetic N-hydroxylated tetraamine derivative. It was found that reduction, oxidation and water elimination occurred during APCI to generate the corresponding amine, N-oxide, and imine. The investigation further revealed that decomposition of hydroxylamines during APCI depends upon the concentration of the analyte and on the acidity of the solution introduced into the ionization source. The pH-dependence of decomposition was utilized for the development of an MS method that allows for the unambiguous identification of N[bond]OH functionalities. This method was applied for the study of natural products including polyamine toxins from the venom of the spider Agelenopsis aperta and mayfoline, a cyclic polyamine derivative of the shrub Maytenus buxifolia. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_3b95320b559ed96a1cb0fcb5b51d7573 Wed, 25 Nov 2009 21:41:00 -0800 http://dx.doi.org/10.1002%2Fjms.1700 Recombinant monoclonal antibodies (MAbs) can be heterogeneous due to modifications that can occur during expression, purification or during storage. These large multichain proteins ([sim]150 kDa) are structurally challenging for detailed characterization to identify the sites of modifications. We report the use of LTQ Orbitrap mass spectrometry to accurately measure the average masses of individual glycoforms by direct infusion of an intact antibody. To identify the site-specific modification of methionines in the antibody caused by forced oxidation, we used a 'middle-down' approach. The antibody was subjected to limited digestion using the endoproteinase Lys-C and reduced to generate Fab heavy chain, single chain Fc and light chain fragments ([sim]25 kDa each). These species were subjected to on-line liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) analysis using an LTQ Orbitrap, where these large precursors were dissociated by higher-energy collisions in the C-trap. High resolution and accuracy achieved for resulting fragments allowed us to show in a site-specific manner that only the methionines in the Fc heavy chain were oxidized under the studied conditions. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_467da1d5aecded982848edb1a8734e4e Wed, 25 Nov 2009 21:41:00 -0800 http://dx.doi.org/10.1002%2Fjms.1699 An information-rich on-target performic acid oxidation method, which is compatible with alkylation for differentiation of free cysteine versus disulfide-containing peptides, is described. On-target oxidation is achieved using performic acid vapor to oxidize disulfide-containing peptides and/or small proteins on the matrix-assisted laser desorption/ionization (MALDI) sample deposits. The on-target oxidation method is preferred over solution-phase oxidation methods because (1) less sample handing is required, (2) oxidation throughput is drastically increased and (3) ion suppression effects are reduced because performic acid is not added directly to the MALDI spot. The utility of this method is demonstrated by simultaneous oxidation of multiple MALDI sample deposits containing model disulfide-linked peptides, intact bovine insulin and a bovine ribonuclease A proteolytic digest. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_a6cc49b93a5f062e5d5dea25365b22f2 Mon, 23 Nov 2009 19:52:00 -0800 http://dx.doi.org/10.1002%2Fjms.1698 Peptide samples derived from enzymatic in-gel digestion of proteins resolved by gel electrophoresis often contain high amount of salts originating from reaction and separation buffers. Different methods are used for desalting prior to matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS), e.g. reversed-phase pipette tip purification, on-target washing, adding co-matrices, etc. As a suitable matrix for MALDI MS of peptides, [alpha]-cyano-4-hydroxycinnamic acid (CHCA) is frequently used. Crystalline CHCA shows the ability to bind peptides on its surface and because it is almost insoluble in acidic water solutions, the on-target washing of peptide samples can significantly improve MALDI MS signals. Although the common on-target washing represents a simple, cheap and fast procedure, only a small portion of the available peptide solution is efficiently used for the subsequent MS analysis. The present approach is a combination of the on-target washing principle carried out in a narrow-end pipette tip (e.g. GELoader tip) and preconcentration of peptides from acidified solution by passing it through small CHCA crystals captured inside the tip on a glass microfiber frit. The results of MALDI MS analysis using CHCA-tip peptide preconcentration are comparable with the use of homemade POROS R2 pipette tip microcolumns. Advantages and limitations of this approach are discussed. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_ce5ca7a170087de98ede552d16ba8e2a Wed, 18 Nov 2009 22:28:00 -0800 http://dx.doi.org/10.1002%2Fjms.1697 Proteins in the nucleus accumbens mediate many cocaine-induced behaviors. In an effort to measure changes in nucleus accumbens protein expression as potential biomarkers for addiction, coronal tissue sections were obtained from rats that developed behavioral sensitization after daily administration of cocaine, or from daily saline-treated controls. The tissue sections were subjected to matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) profiling and tissue imaging. For profiling experiments, brain sections were manually spotted with matrix over the nucleus accumbens, a brain region known to regulate cocaine sensitization. Summed mass spectra (10 000 laser shots, grid) were acquired and spectra were aligned to reference peaks. Using bioinformatics tools, eight spectral features were found to be altered by cocaine treatment. Based on additional sequencing experiments with MALDI tandem MS and database searches of measured masses, secretoneurin (m/z 3653) was identified as having an increased expression. In addition, the distribution of m/z 3653 in the nucleus accumbens was determined by MALDI tissue imaging, and the increased expression of its precursor protein, secretogranin II, was verified by immunoblotting. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_a142dd8d6daa3e448b02831d9dbdb886 Mon, 16 Nov 2009 00:43:00 -0800 http://dx.doi.org/10.1002%2Fjms.1695 Parkinson's disease (PD) is a very serious neurological disorder, and current methods of treatment fail to achieve long-term control. SCH 420814 is a potent, selective and orally active adenosine A2A receptor antagonist discovered by Schering-Plough. Stability testing provides evidence of the quality of a bulk drug when exposed to the influence of environmental factors. Understanding the drug degradation profiles is critical to the safety and potency assessment of the drug candidate for clinical trials. As a result, identification of degradation products has taken an important role in drug development process. In this study, a rapid and sensitive method was developed for the structural determination of the degradation products of SCH 420814 formed under different forced conditions. The study utilizes a combination of liquid chromatography-tandem-mass spectrometry (LC-MS/MS) and Fourier Transform (FT) MS techniques to obtain complementary information for structure elucidation of the unknowns. This combination approach has significant impact on degradation product identification. A total of ten degradation products of SCH 420814 were characterized using the developed method. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_ff7e36ad68af28ecbbd6cbd5ea3c1ad9 Wed, 11 Nov 2009 23:50:00 -0800 http://dx.doi.org/10.1002%2Fjms.1693 The reactions of resonant electron capture by the molecules of benzene nitroderivatives has been studied in the gas phase. Some fragment negative ions were found to be unstable with respect to electron autodetachment. This circumstance has been used for the determination of their structure. In particular, it has been established that the low measured appearance energy of neutral component of [M[bond]H]- ion beam is a result of isomerization of nitrobenzenes' molecular ion, leading to the 2-nitrosophenol structure with the subsequent formation of the phenoxide anion in the autodetaching state. The effective yield curves of some types of fragment ions demonstrate fine vibrational structures, testifying the predissociation mechanism of ion formation. For all detected ions, the absolute cross sections of formation have been measured. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_b022a93bcd7b5b1c0b1773a97b8e5dcb Mon, 09 Nov 2009 01:02:00 -0800 http://dx.doi.org/10.1002%2Fjms.1687 Disposable plasticware such as plastic test tubes are routinely used in all proteomics laboratories. Additives in polymers are used to protect them against oxygen or ultraviolet (UV) light degradation. Hindered amine light stabilizers (HALSs) are of utmost importance in modern polyolefin (polypropylene, polyethylene) stabilization. In this article, we demonstrate that the manufacturing polymeric agent: poly-(N-[beta]-hydroxyethyl-2,2,6,6-tetramethyl-4-hydroxy-piperidinyl succinate), known as Tinuvin-622 or Lowilite 62, from the HALS family, leaches from laboratory polypropylene or polyethylene plastic test tubes into the standard solvents for sample preparation. The analysis of these polluted samples by matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF) mass spectrometry, in the positive mode, shows highly contaminated mass spectra, due to the high sensitivity of this technique. These contaminants have mass range and mass defect similar to those of peptides arising from the digestion of a protein in a conventional proteomics study. Therefore, they can be really harmful for proteomics studies, leading to misattributions, preventing any protein identification. In this article, an MS and MS/MS fingerprint of this pollutant is given and some pieces of advice to avoid it are proposed. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_a34cc8b525a84108021df1ced668296b Thu, 05 Nov 2009 22:14:00 -0800 http://dx.doi.org/10.1002%2Fjms.1689 A sensitive LC/MS/MS method has been developed by derivatization of 17[beta]-estradiol (E2) with dansyl chloride to quantitate 17[beta]-E2 in female rat serum. The use of E2-d5 minimized interferences from endogenous 17[beta]-E2 in order to achieve a limit of quantitation (LOQ) of 2.5 pg/ml using 150 µl of female rat serum. The recovery of the dansyl derivative was 95% or greater in quality control samples. The intra and interday assay precision was better than 8.2 and 6.2%, respectively, with accuracies ranging from 97 to 101% in the quality control samples. The assay was used for the quantitation of serum E2 as a biomarker for the estrogen receptor (ER) antagonist activity of small molecule SERMs (selective estrogen receptor modulators) in the female rat brain. The study revealed that a statistically significant upregulation of serum 17[beta]-E2 occurred for rats dosed with SERMs that are known to penetrate the brain and disrupt the hypothalamic-pituitary-ovarian (HPO) axis. Variations in 17[beta]-E2 in ascending dose studies also correlated with the corresponding trends in CYP17a1 levels, an mRNA biomarker for ovarian hyperstimulation. This biomarker assay has provided a useful screen for medicinal chemistry optimization to produce SERMs that do not interfere with negative feedback of estrogens on the brain and for biological hypothesis testing. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_e7ee7e978df827e9bb0857aca162ae8b Sun, 01 Nov 2009 19:50:00 -0800 http://dx.doi.org/10.1002%2Fjms.1690 Upon collision-induced activation, gaseous sodium adducts generated by electrospray ionization of disodium salts of 1,2- 1,3-, and 1,4-benzene dicarboxylic acids (m/z 233) undergo an unprecedented expulsion of CO2 by a rearrangement process to produce an ion of m/z 189 in which all three sodium atoms are retained. When isolated in a collision cell of a tandem-in-space mass spectrometer, and subjected to collision-induced dissociation (CID), only the m/z 189 ions derived from the meta and para isomers underwent a further CO2 loss to produce a peak at m/z 145 for a sodiated arene of formula (Na3C6H4)+. This previously unreported m/z 145 ion, which is useful to differentiate meta and para benzene dicarboxylates from their ortho isomer, is in fact the sodium adduct of phenelenedisodium. Moreover, the m/z 189 ion from all three isomers readily expelled a sodium radical to produce a peak at m/z 166 for a radical cation [([bull]C6H4CO2Na2)+], which then eliminated CO2 to produce a peak at m/z 122 for the distonic cation ([bull]C6H4Na2)+. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_09c6157f64a3f2d445c52dc7530c5206 Fri, 30 Oct 2009 00:01:00 -0700 http://dx.doi.org/10.1002%2Fjms.1688 The mononuclear complex Pd(1-TosC-N3)2Cl2 (2) containing 1-(p-toluenesulfonyl)cytosine (1) as a ligand, as well as dinuclear complexes Pd2(1-TosC--N3,N4)4 (3) and Pd2(1-TosC--N3,N4)2DMSO2Cl2 (4) containing the ligand anion (1-TosC-), was mass analyzed by electrospray ionization ion trap MS/MS and high resolution MS. Complexes 3 and 4 were obtained by recrystallization of 2 from DMF and DMSO, respectively. The behavior of complex 2 in different solutions was monitored by electrospray ionization mass spectrometry (ESI-MS). Under the applied ESI-MS conditions, complex 2 in methanol reorganized itself dominantly as new complex 3 and the solvent did not coordinate the formed species. In H2O/DMSO, CH3CN/DMSO and CH3OH/DMSO solutions, complex 2 formed several new species with solvent molecules involved in their structure, e.g. complex 4 was formed as the major product. The newly formed species were also examined by LC-MS-DAD, confirming the solvent induced reorganization and the solution instability of complex 2. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_ae709220837c4685ed00fab1c354fd13 Fri, 30 Oct 2009 00:02:00 -0700 http://dx.doi.org/10.1002%2Fjms.1686 Electrospray ionization mass spectrometry (ESI/MS) has allowed the discovery of novel dimer ions emerging from solutions of metalloporphyrin salts and their investigation by collision-induced dissociation (CID) with N2 molecules. ESI mass spectra have been recorded for the formation of the oxygen or chloride-bridged dimer ions [(FeTPP)2OH]+, [(MnTPP)2OH]+, [(FeTPP)2Cl]+ and [(MnTPP)2Cl]+ derived from various solutions of FeTPPCl and MnTPPCl salts. The CID of [(FeTPP)2OH]+ proceeds mainly by neutral loss of (FeTPP)OH to form [FeTPP]+ and, to a minor extent, to form the charge-reversed products. The CID of [(MnTPP)2OH]+ exhibits exclusively the product ion [MnTPP]+ by loss of neutral (MnTPP)OH. [(FeTPP)2Cl]+ and [(MnTPP)2Cl]+ dissociate by loss of (Fe/MnTPP)Cl to give rise to [Fe/MnTPP]+. [(FeTPP)2O]+ and [(FeTPP)2OH]+ were generated from a solution of the dimer, (FeTPP)2O. Dissociation of [(FeTPP)2O]+ yields two product ions, [FeTPP]+ and [(FeTPP)O]+, with higher onsets compared to the equivalent fragments formed from [(FeTPP)2OH]+. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_8e7ecbed50d10e96d69f3d58f3a53f79 Tue, 27 Oct 2009 03:40:00 -0700 http://dx.doi.org/10.1002%2Fjms.1684 In recent years, it has become increasingly interesting to understand the performance of mass spectrometers at pressures much higher than those employed with conventional operating conditions. This interest has been driven by several influences, including demand for the development of reduced-power miniature mass spectrometers, desire for improved ion transfer into and through mass spectrometers, enhanced-yield preparative mass separations, and mass filtering at the atmospheric pressure interface. In this study, an instrument was configured to allow for the performance characterization of a rectilinear ion trap (RIT) at pressures up to 50 mtorr with air used as the buffer gas. The mass analysis efficiency, mass resolution, isolation efficiency, and collision-induced dissociation (CID) efficiency were evaluated at pressures ranging from 1 to 50 mtorr. The extent of degradation of mass resolution, isolation efficiency and ion stability as functions of pressure were characterized. Also, the optimal resonance ejection conditions were obtained at various pressures. Operations at 50 mtorr demonstrated improved CID efficiency in addition to peak widths of 2 and 5 m/z units (full width at half-maximum, FWHM) for protonated caffeine (m/z 195) and Ultramark (m/z 1521) respectively. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_aea5c2de082e0f18a02374ff52197882 Tue, 27 Oct 2009 03:40:00 -0700 http://dx.doi.org/10.1002%2Fjms.1683 Four co-eluting components, with experimentally measured Mr of 23 658, 23 786, 24 278 and 24 406 Da, were detected by reversed-phase high-performance liquid chromatography (RP-HPLC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis in the dephosphorylated casein fraction of a milk sample collected at middle lactation stage from an individual donkey belonging to the Ragusano breed. By coupling RP-HPLC, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), enzymatic digestions, MALDI-TOF MS and capillary RP-HPLC/nano-electrospray ionization tandem mass spectrometry (nESI-MS/MS) analyses, the four components were identified as donkey's [alpha]s1-CNs and their sequences completely characterized, using the known mare's [alpha]s1-CN (GenBank Acc. No. AAK83668; Mr 23750.7 Da) as reference. The proteins with Mr of 23 786 and 23 658 Da differ in the presence of a glutamine residue at position 83 in the full-length component and present the amino acid substitutions Q8[rarr]H and H115[rarr]Y with respect to the mare's [alpha]s1-CN. The other two components with Mr 24 406 and 24 278 Da, which also differ in the presence of a glutamine residue at position 88 in the full-length component, show the insertion of the pentapeptide HTPRE between Leu33 and the Glu34. The two [alpha]s1-CNs bearing the pentapeptide insertion were named variants A (202 amino acids; Mr 24 406) and A1 (201 amino acids; Mr 24 278), whereas the two [alpha]s1-CNs without the pentapeptide were named variants B (197 amino acids; Mr 23 786) and B1 (196 amino acids; Mr 23 658). Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_4d23154bcafa38c27fbe7d375c56f46a Tue, 27 Oct 2009 03:39:00 -0700 http://dx.doi.org/10.1002%2Fjms.1685 The validity of the urinary protein profile to characterize the pathological states of diabetic, nephropathic and diabetic-nephropathic patients was considered on the basis of previously obtained results by MALDI/MS, showing a different abundance ratio of the collagen [alpha]1 and [alpha]5 chain precursor fragments at m/z 1219 and 2049 and of the uromodulin precursor fragment at m/z 1912 observed in healthy subjects and patients; a larger number of subjects was examined and the obtained results were statistically evaluated. The p values related to the observed differences indicate that they are statistically significant when comparing all patients versus healthy controls, diabetic with normo or microalbuminuria versus nephropathic with advanced renal disease patients and diabetic with normo or microalbuminuria versus diabetic with advanced nephropathy patients. The scatter plot matrix gives evidence of the strict inverse relationship between the abundances of ions at m/z 1912 and 1219, the correlation coefficient being particularly high (r = 0.921, p &lt; 0.001). The relationship between the true positive rate (sensitivity) and false positive rate (1 - specificity) for every possible cutoff value in abundance of the considered ionic species was investigated through the receiver-operating characteristic (ROC) curve. The obtained data indicate that a good differentiation of nephropathic patients with advanced renal disease and diabetic patients with advanced nephropathy versus healthy subjects can be easily obtained by this approach. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_ed95b04e3ff2bf04ee6b5b4f7f59acc7 Thu, 22 Oct 2009 03:37:00 -0700 http://dx.doi.org/10.1002%2Fjms.1677 Three lipocyclopeptide antibiotics, aspartocins A (1), B (2), and C (3), were obtained from the aspartocin complex by HPLC separation methodology. Their structures were elucidated using previously published chemical degradation results coupled with spectroscopic studies including ESI-MS, ESI-Nozzle Skimmer-MSMS and NMR. All three aspartocin compounds share the same cyclic decapeptide core of cyclo [Dab2 (Asp1-FA)-Pip3-MeAsp4-Asp5-Gly6-Asp7-Gly8-Dab9-Val10-Pro11]. They differ only in the fatty acid side chain moiety (FA) corresponding to (Z)-13-methyltetradec-3-ene-carbonyl, (+,Z)-12-methyltetradec-3-ene-carbonyl and (Z)-12-methyltridec-3-ene-carbonyl for aspartocins A (1), B (2), and C (3), respectively. All of the sequence ions were observed by ESI-MSMS of the doubly charged parent ions. However, a number of the sequence ions observed were of low abundance. To fully sequence the lipocyclopeptide antibiotic structures, these low abundance sequence ions together with complementary sequence ions were confirmed by ESI-Nozzle-Skimmer-MSMS of the singly charged linear peptide parent fragment ions H-Asp5-Gly6-Asp7-Gly8-Dab9-Val10-Pro11-Dab21+-Asp1-FA. Cyclization of the aspartocins was demonstrated to occur via the [beta]-amino group of Dab2 from ions of moderate intensity in the ESI-MSMS spectra. As the fatty acid moieties do not undergo internal fragmentations under the experimental ESI mass spectral conditions used, the 14 Da mass difference between the fatty acid moieties of aspartocins A (1) and B (2) versus aspartocin C (3) was used as an internal mass tag to differentiate fragment ions containing fatty acid moieties and those not containing the fatty acid moieties. The most numerous and abundant fragment ions observed in the tandem mass spectra are due to the cleavage of the tertiary nitrogen amide of the pipecolic acid residue-3 (16 fragment ions) and the proline residue-11 (7 fragment ions). In addition, the neutral loss of ethanimine from [alpha],[beta]-diaminobutyric acid residue 9 was observed for the parent molecular ion and for 7 fragment ions. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_9dd4af1bf16f96a4eb97bdb3544c7fd2 Fri, 16 Oct 2009 01:17:00 -0700 http://dx.doi.org/10.1002%2Fjms.1681 Commercial copper wire and its polymer insulation cladding was investigated for the presence of three synthetic antioxidants (ADK STAB AO412S, Irganox 1010 and Irganox MD 1024) by three different mass spectrometric techniques including electrospray ionization-ion trap-mass spectrometry (ESI-IT-MS), matrix-assisted laser desorption/ionization reflectron time-of-flight (TOF) mass spectrometry (MALDI-RTOF-MS) and reflectron TOF secondary ion mass spectrometry (RTOF-SIMS). The samples were analyzed either directly without any treatment (RTOF-SIMS) or after a simple liquid/liquid extraction step (ESI-IT-MS, MALDI-RTOF-MS and RTOF-SIMS). Direct analysis of the copper wire itself or of the insulation cladding by RTOF-SIMS allowed the detection of at least two of the three antioxidants but at rather low sensitivity as molecular radical cations and with fairly strong fragmentation (due to the highly energetic ion beam of the primary ion gun). ESI-IT- and MALDI-RTOF-MS-generated abundant protonated and/or cationized molecules (ammoniated or sodiated) from the liquid/liquid extract. Only ESI-IT-MS allowed simultaneous detection of all three analytes in the extract of insulation claddings. The latter two so-called 'soft' desorption/ionization techniques exhibited intense fragmentation only by applying low-energy collision-induced dissociation (CID) tandem MS on a multistage ion trap-instrument and high-energy CID on a tandem TOF-instrument (TOF/RTOF), respectively. Strong differences in the fragmentation behavior of the three analytes could be observed between the different CID spectra obtained from either the IT-instrument (collision energy in the very low eV range) or the TOF/RTOF-instrument (collision energy 20 keV), but both delivered important structural information. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_f00fde71feaae21bafd3e4f623171afd Wed, 14 Oct 2009 03:07:00 -0700 http://dx.doi.org/10.1002%2Fjms.1680 One of the main objectives of wheat glutenin subunit (GS) analysis is the identification of protein components linked to wheat quality. The proteomic characterization of glutenin has to consider the relatively low levels of arginine and lysine residues and the close sequence similarity among the different groups of these subunits, which hinders or even prevents the identification of the GS. In this study, a proteomic approach has been applied to resolve the heterogeneity of wheat glutenin components. Proteins extracted from Triticum durum flour were first analyzed by two-dimensional gel electrophoresis, which greatly reduced glutenin complexity. The identity of each spot was confirmed by nano liquid chromatography tandem mass spectrometry analysis of tryptic peptides. In parallel, measurements of the high mass range by matrix-assisted laser desorption/ionization time-of-flight analysis allowed detection of the large tryptic peptides. Gathering all data from search engine interrogation, very high sequence coverage was obtained for high molecular weight GS, including Bx7 and By8, in agreement with the known genetic profile of durum wheat. In addition, a truncated form of By8, never detected before, was also found. Low molecular weight GS (LMW-GS) B-type was identified with reasonable sequence coverage, while a clear identification of LWM-GS C- and D-type was hindered by the incompleteness of the wheat DNA databases. This study represents the first comprehensive analysis of the glutenin proteome and provides a reliable method for classifying wheat varieties according to their glutenin profile. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_f4b8553ddb915c5f1be672513e727b72 Wed, 14 Oct 2009 03:07:00 -0700 http://dx.doi.org/10.1002%2Fjms.1682 Fragmentation reactions of [beta]-hydroxymethyl-, [beta]-acetoxymethyl- and [beta]-benzyloxymethyl-butenolides and the corresponding [gamma]-butyrolactones were investigated by electrospray ionization tandem mass spectrometry (ESI-MS/MS) using collision-induced dissociation (CID). This study revealed that loss of H2O [M + H -18]+ is the main fragmentation process for [beta]-hydroxymethylbutenolide (1) and [beta]-hydroxymethyl-[gamma]-butyrolactone (2). Loss of ketene ([M + H -42]+) is the major fragmentation process for protonated [beta]-acetoxymethyl-[gamma]-butyrolactone (4), but not for [beta]-acetoxymethylbutenolide (3). The benzyl cation (m/z 91) is the major ion in the ESI-MS/MS spectra of [beta]-benzyloxymethylbutenolide (5) and [beta]-benzyloxymethyl-[gamma]-butyrolactone (6). The different side chain at the [beta]-position and the double bond presence afforded some product ions that can be important for the structural identification of each compound. The energetic aspects involved in the protonation and gas-phase fragmentation processes were interpreted on the basis of thermochemical data obtained by computational quantum chemistry. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_5b8112a6e9740225e38304750033cf18 Tue, 13 Oct 2009 03:17:00 -0700 http://dx.doi.org/10.1002%2Fjms.1678 Five glucosylceramides (GlcCers) were isolated by reversed phase high-performance liquid chromatography from the MeOH extracts of a marine sponge, Haliclona (Reniera) sp., collected from the coast of Ulleung Island, Korea, and analyzed by fast atom bombardment mass spectrometry (FAB-MS) in positive-ion mode. FAB-mass spectra of these compounds included protonated molecules [M + H]+ and abundant sodiated molecules [M + Na]+ from a mixture of m-NBA and NaI. The structures of these GlcCers, which were similar, were elucidated by FAB-linked scan at constant B/E. To find diagnostic ions for their characterization, the GlcCers were analyzed by collision-induced dissociation (CID) linked scan at constant B/E. The CID-linked scan at constant B/E of [M + H]+ and [M + Na]+ precursor ions resulted in the formation of numerous characteristic product ions via a series of dissociative processes. The product ions formed by charge-remote fragmentation provided important information for the characterization of the fatty N-acyl chain moiety and the sphingoid base, commonly referred to as the long-chain base. The product ions at m/z 203 and 502 were diagnostic for the presence of a sodiated sugar ring and [beta]-D-glucosylsphinganine, respectively. For further confirmation of the structure of the fatty N-acyl chain moiety in each GlcCer, fatty acid methyl esters were obtained from the five GlcCers by methanolysis and analyzed by FAB-MS in positive-ion mode. On the basis of these dissociation patterns, the structures of the five GlcCers from marine sponge were elucidated. In addition, the accurate mass measurement was performed to obtain the elemental composition of the GlcCers isolated from marine sponge. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_17b87c0ed885a8312823b28139d5e6a7 Mon, 12 Oct 2009 04:33:00 -0700 http://dx.doi.org/10.1002%2Fjms.1672 Benzylpyridinium ions are often used as 'thermometer ions' in order to evaluate the internal energy distribution of the ions formed in sources of mass spectrometers. However, the detailed fragmentation pathways of these parent ions were not well established. In particular, fragmentation involving a rearrangement (RR) process may be influencing the simulated distribution curves. In a previous study, we suggested that such RR actually occurred under electrospray ionization/mass spectrometry (ESI/MS) and fast atom bombardment/mass spectrometry (FAB/MS) experiments. Here, we present a systematic study of different substituted benzylpyridinium ions. Theoretical calculations showed that RR fragmentation leading to substituted tropylium ions could occur under 'soft ionization' conditions, such as ESI or FAB. Experimental results obtained under gas-phase reactivity conditions showed that some substituted benzylpiridinium compounds actually undergo RR fragmentations under ESI/MS conditions. Mass-analyzed kinetic experiments were also carried out to gain information on the reaction pathways that actually occur, and these experimental results are in agreement with the reaction pathways theoretically proposed. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_52e0d5f2ef99107bef1fb3caacbc5e8d Mon, 12 Oct 2009 04:33:00 -0700 http://dx.doi.org/10.1002%2Fjms.1631 Saffron is one of the oldest natural dyestuffs and is obtained from the dried stigmata of Crocus sativus L. Nowadays, saffron is considered as an invaluable spice of golden-yellow hue, a precious ingredient in the Eastern and Mediterranean cuisines. It is characterized by a bitter taste that is caused by the chemical properties of its constituents. The yellowness of saffron results from the presence of crocins (glycosyl esters of crocetin), its main color compounds, which are examined in the present study in the crude methanol extracts by high performance liquid chromatography (HPLC) coupled with spectrophotometric and electrospray mass spectrometric detection (HPLC-UV-Vis-ESI MS). This technique allowed the separation and identification of trans- and cis-isomers of crocins. Their mass spectra registered in the negative ion mode comprised the quasi-molecular and fragment ions, as well as a range of other ions. Doubly charged ions were found for trans-isomers only, due to the high symmetry of their molecules. Modification of the eluent allowed the identification of several signals corresponding to adduct ions of crocins with the used additives. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_8593f49a6095fbb3a4eedd74e17cdd1b Thu, 08 Oct 2009 20:50:00 -0700 http://dx.doi.org/10.1002%2Fjms.1673 A new software tool called lipID is reported, which supports the identification of glycerophospholipids, glycosphingolipids, fatty acids and small oligosaccharides in mass spectra. The user-extendable software is a Microsoft (MS) Excel Add-In developed using Visual Basic for Applications and is compatible with all Versions of MS Excel since MS Excel 97. It processes singly given mass-to-charge values as well as mass lists considering a number of user-defined options. The software's mode of operation, usage and options are explained and the benefits and limitations of the tool are illustrated by means of three typical analytical examples of lipid analyses. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_f9bcb4c070515c65c22be2201f3cebe3 Wed, 07 Oct 2009 21:43:00 -0700 http://dx.doi.org/10.1002%2Fjms.1679 No Abstract. wKB6qta72xGqBxWCkAtvUw_77dbe4beaf0db24ac6cecd7070c02f52 Fri, 02 Oct 2009 04:31:00 -0700 http://dx.doi.org/10.1002%2Frcm.4318 The study of hyper-velocity impacts of micrometeoroids is important for the calibration of dust sensors in space applications. For this purpose, submicron-sized synthetic dust grains comprising either polystyrene or poly[bis(4-vinylthiophenyl)sulfide] were coated with an ultrathin overlayer of an electrically conductive organic polymer (either polypyrrole or polyaniline) and were accelerated to speeds between 3 and 35 km s-1 using the Heidelberg Dust Accelerator facility. Time-of-flight mass spectrometry was applied to analyse the resulting ionic impact plasma using a newly developed Large Area Mass Analyser (LAMA). Depending on the projectile type and the impact speed, both aliphatic and aromatic molecular ions and cluster species were identified in the mass spectra with masses up to 400 u. Clusters resulting from the target material (silver) and mixed clusters of target and projectile species were also observed. Impact velocities of between 10 and 35 km s-1 are suitable for a principal identification of organic materials in micrometeoroids, whereas impact speeds below [sim]10 km s-1 allow for an even more detailed analysis. Molecular ions and fragments reflect components of the parent molecule, providing determination of even complex organic molecules embedded in a dust grain. In contrast to previous measurements with the Cosmic Dust Analyser instrument, the employed LAMA instrument has a seven times higher mass resolution - approximately 200 - which allowed for a detailed analysis of the complex mass spectra. These fundamental studies are expected to enhance our understanding of cometary, interplanetary and interstellar dust grains, which travel at similar hyper-velocities and are known to contain both aliphatic and aromatic organic compounds. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_901073b93a32ad6904462e0b2b9fe6e0 Tue, 17 Nov 2009 19:46:00 -0800 http://dx.doi.org/10.1002%2Frcm.4329 Hepatotoxic pyrrolizidine alkaloid (HPA)-containing plants have always been a threat to human and livestock health worldwide. Adonifoline, a main HPA in Senecio scandens Buch.-Ham. ex D. Don (Qianli guang), was used officially as an infusion in cases of oral and pharyngeal infections in China. In this study in vivo metabolism of adonifoline was studied for the first time by identifying the metabolites of adonifoline present in bile, urine and feces of rats using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MSn) (ion trap) as well as liquid chromatography/electrospray ionization high-resolution mass spectrometry (LC/ESI-HRMS) (quadrupole-time of flight). In total 19 metabolites were identified and, among them, retronecine-N-oxides were confirmed by matching their fragmentation patterns with their fully characterized synthetic compounds. These metabolites are all involved in both phase I and phase II metabolic processes and the principal in vivo metabolism pathways of adonifoline were proposed. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_5fcc3bb52445b0db8551aa349b7b8a4e Sun, 15 Nov 2009 21:41:00 -0800 http://dx.doi.org/10.1002%2Frcm.4326 The aim of this study was to investigate the utility of ion trap mass spectrometry (ITMS) in combination with the two desorption/ionization methods, electrospray (ESI) and atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI), for the detection of antioxidants which are applied in lubricants. These experiments should form the base for future investigations of antioxidants in tribologically formed thin layers on the surface of frictional systems. Seventeen different antioxidants were selected out of the group of hindered phenolic and aromatic aminic compounds. Practically all antioxidants could be characterized by positive ion ESI- and AP-MALDI-ITMS, forming various types/species of molecular ions (e.g. [M]+., [M+H]+, [M+Na]+ or [M-2H+H]+). A few compounds could be analyzed by negative ion ESI-MS, too, but none by negative ion AP-MALDI-MS. The influence of target materials in AP-MALDI-MS (gold- and titanium nitride (TiN)-covered stainless steel, micro-diamond-covered hard metal, hand-polished and sand-blasted stainless steel targets) with respect to the molecular ion intensity and type of molecular ion of two selected antioxidants was evaluated. The surface properties are of particular interest because in friction tests different materials with different surface characteristics are used. However, the MS results indicate that optimal target surfaces have to be found for individual antioxidants in AP-MALDI-MS but in general smooth surfaces were superior to rough surfaces. Finally the gold-covered stainless steel MALDI target provided the best mass spectra and was selected for all the antioxidants investigated. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_b4ca7b394d9d2c0d7f130e747a5092f7 Tue, 17 Nov 2009 19:47:00 -0800 http://dx.doi.org/10.1002%2Frcm.4330 Penicillium expansum is a ubiquitous species for which there are only few reports for chemical investigation in marine environments. Among the numerous secondary metabolites produced by this species, communesins represent a new class of cytotoxic and insecticidal indole alkaloids. In this study, we investigated a marine P. expansum strain exhibiting neuroactivity on a Diptera larvae bioassay. Bio-guided purification led to the isolation and the identification of communesin B as the main active compound by HRMS and 1H and 13C NMR. Liquid chromatography analyses with detection by electrospray ionization coupled with tandem mass spectrometry (LC/ESI-MS/MS) and high-resolution tandem mass spectrometry (LC/HRMS/MS) allowed the identification and characterization of four other known communesins (A, D, E and F) in the crude extract. A fragmentation model for dimethyl epoxide communesins was proposed after detailed interpretation of their MS/MS spectra. Further analyses of the extract using the modelled fragmentations led to the detection of seven new communesins found as minor compounds. Chemical structural elucidation of these new derivatives is discussed based on their fragmentation characteristics. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_6fe7f644f6056129446e9668f27e2d0e Sun, 15 Nov 2009 21:43:00 -0800 http://dx.doi.org/10.1002%2Frcm.4335 A simple and rapid method has been used for the screening and identification of the main phenolic compounds from Helichrysum devium using high-performance liquid chromatography with on-line UV and electrospray ionization mass spectrometric detection (LC-DAD/ESI-MSn). The total aerial parts and different morphological parts of the plant, namely leaves, flowers and stems, were analyzed separately. A total of 34 compounds present in the methanolic extract from Helichrysum devium were identified or tentatively characterized based on their UV and mass spectra and retention times. Three of these compounds were positively identified by comparison with reference standards. The phenolic compounds included derivatives of quinic acid, O-glycosylated flavonoids, a caffeic acid derivative and a protocatechuic acid derivative. The characteristic loss of 206 Da from malonylcaffeoyl quinic acid was used to confirm the malonyl linkage to the caffeoyl group. This contribution presents one of the first reports on the analysis of phenolic compounds from Helichrysum devium using LC-DAD/ESI-MSn and highlights the prominence of quinic acid derivatives as the main group of phenolic compounds present in these extracts. We also provide evidence that the methanolic extract from the flowers was significantly more complex when compared to that of other morphological parts. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_bd2de6efa8acfbce9236551de6cc3f9a Tue, 17 Nov 2009 19:49:00 -0800 http://dx.doi.org/10.1002%2Frcm.4336 A rapid and reliable method based on ultra-performance liquid chromatography (UPLC) coupled with photodiode-array detection (PDA) and electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-Q-TOF-MS/MS) has been developed for separation and identification of major constituents in extracts of root bark of Pseudolarix kaempferi Gordon (PKG). Identification of the constituents was carried out by interpretation of their retention times, UV absorption spectra, MS and MS/MS spectra, as well as the data provided by authentic standards and literatures. A total of 20 components were separated in only 8.0 min on a small particle size C18 column (1.7 µm). These components included nine diterpene acids, seven glycosides and four triterpenoids, among which pseudolaric acid C-O-[beta]-D-glucopyranoside and pseudolaric acid C2-O-[beta]-D-glucopyranoside were separated and identified for the first time in this study. Furthermore, the fragmentation patterns of the three types of compounds were elucidated for the first time. This established UPLC-PDA/Q-TOF-MS/MS method is reliable and effective for the separation and identification of the 20 compounds and will be useful for quality control of the crude materials of Pseudolarix kaempferi Gordon and their related preparations. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_f3b3e0978520cb3fdded9aa7e27cab39 Sun, 15 Nov 2009 21:45:00 -0800 http://dx.doi.org/10.1002%2Frcm.4331 An online nano-aerosol sample deposition method for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is described in which matrix and analyte particles between 50 and 500 nm are aerodynamically focused onto a tight spot, ca. 200 µm in diameter, on the target plate under vacuum. MALDI analysis of the target is performed without additional sample preparation. The method is evaluated with insulin as the analyte and alpha-cyano-4-hydroxycinnamic acid (CHCA) as the matrix. Two preparation modes are compared with conventional dried-droplet deposition: mixture deposition where a single layer is deposited consisting of particles that contain both matrix and analyte, and layered deposition where an underlayer of matrix particles and an overlayer of analyte particles are deposited separately. Desalting is performed by adding ammonium sulfate to the solution used to generate the matrix aerosol. With mixture deposition, the optimum matrix-to-analyte mole ratio is about 500:1 compared with 5000:1 for the conventional dried-droplet method. With layered deposition, the thicknesses of the matrix and analyte layers are more important determinants of the analyte signal intensity than the matrix-to-analyte mole ratio. Analyte signal intensities are independent of matrix layer thickness above 200 nm, and the optimum analyte signal is obtained with an analyte layer thickness of about 100 nm. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_491492c9931080fd5111e99c6aee9d45 Sun, 15 Nov 2009 21:45:00 -0800 http://dx.doi.org/10.1002%2Frcm.4337 Aminomonosaccharides (glucosamine, galactosamine, and mannosamine) in H2O and D2O were ionized by atmospheric pressure chemical ionization (APCI) and their fragmentation patterns were investigated to identify them. All the aminomonosaccharides showed the same fragment ions but their relative ion intensities were different. Major product ions generated in H2O were [M + H]+, [M + H - H2O]+, and [2M + H - 3H2O]+, while in D2O were [MD6 + D]+, [MD6 + D - D2O]+, and [2MD6 + D - D2O - 2HDO]+. At a high fragmentor voltage above 120 V, the relative ion intensities of the major product ions showed different trends according to the aminomonosaccharides. For the use of H2O as solvent and eluent, the order of the ion intensity ratio of [M + H - H2O]+/[2M + H - 3H2O]+ was galactosamine &gt; mannosamine &gt; glucosamine. When using D2O as solvent and eluent, the order of the ion intensity ratios of [MD6 + D - D2O]+/[MD6 + D]+ and [2MD6 + D - D2O - 2HDO]+/[MD6 + D]+ was mannosamine &gt; galactosamine &gt; glucosamine. It was found that glucosamine, galactosamine, and mannosamine could be distinguished by the specific trends of the major product ion ratios in H2O and D2O. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_50e8ec103bc9c6f1f706804a7b400c0e Sun, 15 Nov 2009 21:46:00 -0800 http://dx.doi.org/10.1002%2Frcm.4340 Polyamines are a class of aliphatic compounds which include putrescine, cadaverine, spermine and spermidine. They are involved in a variety of cellular processes and have been implicated in a number of different pathophysiological mechanisms. Polyamines are volatile compounds having a distinctive odour normally perceived as being unpleasant. The measurement of their abundance has, however, been restricted to compounds present in the aqueous phase. Using selected ion flow tube mass spectrometry (SIFT-MS) we have shown that the polyamines react with the ions H3O+, NO+ and O2+ to form distinctive product ions allowing their levels to be quantified in the vapour phase. The low volatility of spermine did not allow extensive analysis of this compound by SIFT-MS while the adherent properties of cadaverine and putrescine required the use of PTFE transfer lines and couplers. Our data suggested the presence of cadaverine and putrescine in both oral air and the headspace of putrefying bovine muscle, while product ions corresponding to putrescine and spermidine were found in the headspace of human semen. SIFT-MS therefore appears to be a practical means of measuring vapour-phase polyamine levels, having applications in biology, medicine and dentistry, and food science. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_13cf8880c4f31cb27ae1c329395a0b97 Sun, 15 Nov 2009 21:40:00 -0800 http://dx.doi.org/10.1002%2Frcm.4338 Identification of microbial contaminants in drinking water is a challenge to matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) due to low levels of microorganisms in fresh water. To avoid the time-consuming culture step of obtaining enough microbial cells for subsequent MALDI-MS analysis, a combination of membrane filtration and nanoparticles- or microparticles-based magnetic separation is a fast and efficient approach. In this work, the interaction of bacteria and fluidMAG-PAA, a cation-exchange superparamagnetic nanomaterial, was investigated by MALDI-MS analysis and transmission electron microscopy. FluidMAG-PAA selectively captured cells of Salmonella, Bacillus, Enterococcus and Staphylococcus aureus. This capture was attributed to the aggregation of negatively charged nanoparticles on bacterial cell regional surfaces that bear positive charges. Three types of non-porous silica-encapsulated anion-exchange magnetic microparticles (SiMAG-Q, SiMAG-PEI, SiMAG-DEAE) were capable of concentrating a variety of bacteria, and were compared with silica-free, smaller fluidMAG particles. Salmonella, Escherichia coli, Enterococcus and other bacteria spiked in aqueous solutions, tap water and reservoir water were separated and concentrated by membrane filtration and magnetic separation based on these ion-exchange magnetic materials, and then characterized by whole cell MALDI-MS. By comparing with the mass spectra of the isolates and pure cells, bacteria in fresh water can be rapidly detected at 1 × 103 colony-forming units (cfu)/mL. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_8b82a50bde14e2780058df1fdd1a01a8 Sun, 15 Nov 2009 21:48:00 -0800 http://dx.doi.org/10.1002%2Frcm.4339 The absolute photoionization cross-sections of aromatics and aromatic derivatives including toluene, ethylbenzene, n-propylbenzene, o-xylene, m-xylene, p-xylene, 1,3,5-trimethylbenzene, styrene, phenylacetylene, indene, indane, 1-methylnaphthalene, benzyl alcohol and benzaldehyde were measured at the photon energy range from ionization thresholds to 11.7 eV. The experiments were performed by tunable synchrotron vacuum ultraviolet (VUV) photoionization mass spectrometry. Benzene was chosen as a calibration standard, since its photoionization cross-section is well known. Binary liquid mixtures of the investigated molecules and benzene were used in the measurements. Photo-induced fragments from the molecules were also observed, and their photoionization cross-sections are also presented. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_befdf8e890c2ad5d33affebff7a76813 Sun, 15 Nov 2009 21:49:00 -0800 http://dx.doi.org/10.1002%2Frcm.4341 Analyzing brain microdialysate samples by mass spectrometry is challenging due to the high salt content of the artificial cerebral spinal fluid (aCSF), low analyte concentrations and small sample volumes collected. A drug and its major metabolites can be examined in brain microdialysates by targeted approaches such as selected reaction monitoring (SRM) which provides selectivity and high sensitivity. However, this approach is not well suited for metabolite profiling in the brain which aims to determine biotransformation pathways. Identifying minor metabolites, or metabolites that arise from brain metabolism, remains a challenge and, for a drug in early discovery, identification of metabolites present in the brain can provide useful information for understanding the pharmacological activity and potential toxicological liabilities of the drug. A method is described here for rapid metabolite profiling in brain microdialysates that involves sample clean-up using C18 ZipTips to remove salts followed by direct infusion nanoelectrospray with an LTQ/Orbitrap mass spectrometer using real-time internal recalibration. Full scan mass spectra acquired at high resolving power (100 K at m/z 400) were examined manually and with mass defect filtering. Metabolite identification was aided by sub-parts-per-million mass accuracy and structural characterization was accomplished by tandem mass spectrometry (MS/MS) experiments in the Orbitrap or LTQ depending on the abundance of the metabolite. Using this approach, brain microdialysate samples from rats dosed with one of four CNS drugs (imipramine, reboxetine, citalopram or trazodone) were examined for metabolites. For each drug investigated, metabolites, some of which not previously reported in rat brain, were identified and characterized. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_95286ba8eb645aa021540c15ef97db6b Sun, 15 Nov 2009 21:51:00 -0800 http://dx.doi.org/10.1002%2Frcm.4342 Pine bark is an important source of polyphenolic compounds, mainly procyanidins, with reported protective effects against disease. In previous works, barks of two varieties of pine (P. pinaster and P. radiata) were extracted with ethanol, and partially purified to obtain the aqueous fractions (FA), that contained mainly polymeric procyanidins. The mean degree of polymerization was 7.9 for radiata (rFA) and 10.6 for pinaster (pFA). FAs were chromatographed on Sephadex LH-20 by using a gradient of methanol, water and acetone, to render a series of sub-fractions. In this work, the procyanidin compositions of these sub-fractions were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The mass spectra of sub-fractions from FA of P. pinaster showed signals of procyanidin polymers up to tridecamers, whereas for those from P. radiata the maximum degree of polymerization was 15. For this latter case, the MALDI-TOF mass spectra detected the presence of prodelphinidins in a small amount. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_3ff660b5e76721947ff66278c8c048ae Wed, 18 Nov 2009 03:12:00 -0800 http://dx.doi.org/10.1002%2Frcm.4343 The selective capture of target peptides poses a great challenge to modern chemists and biologists, especially when enriching them from proteome samples possessing extremes in concentration dynamic range and sequence diversity. While approaches based on traditional techniques such as biotin-avidin pairing offer versatile tools to design strategies for selective enrichment, problems are still encountered due to sample loss or poor selectivity of enrichment. Here we show that the recently introduced fluorous chemistry approach has attractive properties as an alternative method for selective enrichment. Through appending a perfluorine group to the target peptide, it is possible to dramatically increase the peptide's hydrophobicity and thus enable facile separation of labeled from non-labeled peptides. Use of reversed-phase chromatography allowed for improved peptide recovery in comparison with results obtained using the formerly reported fluorous bonded phase methods. Furthermore, this approach also allowed for on-line separation and identification of both labeled and unlabeled peptides in a single experiment. The net result is an increase in the confidence of protein identification by tandem mass spectrometry (MS2) as all peptides and subsequent information are retained. Successful off-line and on-line enrichment of cysteine-containing peptides was obtained, and high quality MS2 spectra were obtained by tandem mass spectrometry due to the stability of the tag, allowing for facile identification via standard database searching. We believe that this strategy holds great promise for selective enrichment and identification of low abundance target proteins or peptides. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_2200777c94b720bf4df5af420e172e77 Wed, 18 Nov 2009 03:15:00 -0800 http://dx.doi.org/10.1002%2Frcm.4344 N-Demethylation of tropine is an important step in the degradation of this compound and related metabolites. With the purpose of understanding the reaction mechanism(s) involved, it is desirable to measure the 15N kinetic isotope effects (KIEs), which can be accessed through the 15N isotope shift ([Delta][delta]15N) during the reaction. To measure the isotope fractionation in 15N during tropine degradation necessitates the extraction of the residual substrate from dilute aqueous solution without introducing artefactual isotope fractionation. Three protocols have been compared for the extraction and measurement of the 15N/14N ratio of tropine from aqueous medium, involving liquid-liquid phase partitioning or silica-C18 solid-phase extraction. Quantification was by gas chromatography (GC) on the recovered organic phase and [delta]15N values were obtained by isotope ratio measurement mass spectrometry (irm-MS). Although all the protocols used can provide satisfactory data and both irm-EA-MS and irm-GC-MS can be used to obtain the [delta]15N values, the most convenient method is liquid-liquid extraction from a reduced aqueous volume combined with irm-GC-MS. The protocols are applied to the measurement of 15N isotope shifts during growth of a Pseudomonas strain that uses tropane alkaloids as sole source of carbon and nitrogen. The accuracy of the determination of the 15N/14N ratio is sufficient to be used for the determination of 15N-KIEs. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_6664ab41ae1154e8c569296991e56a58 Wed, 18 Nov 2009 03:14:00 -0800 http://dx.doi.org/10.1002%2Frcm.4347 Hexose-modified peptides, products of the enzymatic hydrolysis of glycated proteins, could be used as markers of diabetes mellitus, the aging process and other diseases. The main difficulty in this approach is the detection of glycated peptides in the complex mixtures of compounds. In this study we investigated the formation of borate complexes of the peptide-derived Amadori products by high-resolution mass spectrometry (HRMS) and tandem mass spectrometry (MS/MS) experiments. It was found that the formation of a complex with the borate ion stabilizes the sugar moiety, resulting in the simplification of the fragmentation patterns of peptide-derived Amadori products. The level of dehydration, as well as the elimination of formaldehyde from the precursor ions of borate complexes, was lower as compared to the free peptide. On the other hand the intensity of the b- and y-type ions for borate complexes is significantly higher in comparison to the free peptide-derived Amadori product. Moreover, the elimination of a whole hexose moiety was not detected in the examined peptides. Copyright © 2009 John Wiley & Sons, Ltd. wKB6qta72xGqBxWCkAtvUw_d26308d395b8bd40ac32420e7e183fec Wed, 18 Nov 2009 03:13:00 -0800 http://dx.doi.org/10.1002%2Frcm.4304 No Abstract. wKB6qta72xGqBxWCkAtvUw_94bc69ecbc032338196a7048a2fd894b Wed, 18 Nov 2009 03:21:00 -0800