{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T16:51:34Z","timestamp":1761929494147,"version":"build-2065373602"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2010,3,30]],"date-time":"2010-03-30T00:00:00Z","timestamp":1269907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2010,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Drug bioactivation leading to the formation of reactive species capable of covalent binding to proteins represents an important cause of drug\u2010induced toxicity. Reactive metabolite detection using\n                    <jats:italic>in<\/jats:italic>\n                    <jats:italic>vitro<\/jats:italic>\n                    microsomal incubations is a crucial step in assessing potential toxicity of pharmaceutical compounds. The most common method for screening the formation of these unstable, electrophilic species is by trapping them with glutathione (GSH) followed by liquid chromatography\/mass spectrometry (LC\/MS) analysis. The present work describes the use of a brominated analog of glutathione,\n                    <jats:italic>N<\/jats:italic>\n                    \u2010(2\u2010bromocarbobenzyloxy)\u2010GSH (GSH\u2010Br), for the\n                    <jats:italic>in<\/jats:italic>\n                    <jats:italic>vitro<\/jats:italic>\n                    screening of reactive metabolites by LC\/MS. This novel trapping agent was tested with four drug compounds known to form reactive metabolites, acetaminophen, fipexide, trimethoprim and clozapine.\n                    <jats:italic>In<\/jats:italic>\n                    <jats:italic>vitro<\/jats:italic>\n                    rat microsomal incubations were performed with GSH and GSH\u2010Br for each drug with subsequent analysis by liquid chromatography\/high\u2010resolution mass spectrometry on an electrospray time\u2010of\u2010flight (ESI\u2010TOF) instrument. A generic LC\/MS method was used for data acquisition, followed by drug\u2010specific processing of accurate mass data based on mass defect filtering and isotope pattern matching. GSH and GSH\u2010Br incubations were compared to control samples using differential analysis (Mass Profiler) software to identify adducts formed via the formation of reactive metabolites. In all four cases, GSH\u2010Br yielded improved results, with a decreased false positive rate, increased sensitivity and new adducts being identified in contrast to GSH alone. The combination of using this novel trapping agent with powerful processing routines for filtering accurate mass data and differential analysis represents a very reliable method for the identification of reactive metabolites formed in microsomal incubations. Copyright \u00a9 2010 John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/rcm.4507","type":"journal-article","created":{"date-parts":[[2010,3,30]],"date-time":"2010-03-30T03:29:35Z","timestamp":1269919775000},"page":"1241-1250","source":"Crossref","is-referenced-by-count":46,"title":["Improved detection of reactive metabolites with a bromine\u2010containing glutathione analog using mass defect and isotope pattern matching"],"prefix":"10.1002","volume":"24","author":[{"given":"Andr\u00e9","family":"LeBlanc","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tze Chieh","family":"Shiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lekha","family":"Sleno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,4,7]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1081\/DMR-200028812"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2005.12.007"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/15287399409531852"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx700186p"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx034170b"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/jms.1098"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2008.09.014"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/bms.1200220602"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx049741u"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac702232r"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/jms.1610"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac071119u"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.3504"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.3953"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.2195"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx0496791"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx050303c"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2004.04.019"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo971176v"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/20014091111677"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/00045391-200007020-00011"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(87)90069-4"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1159\/000136531"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.3109\/03602539709037573"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(90)90174-S"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.3092"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.3329"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1185\/03007998609110426"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1984.tb02460.x"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(92)90027-M"},{"key":"e_1_2_6_32_2","first-page":"429","volume":"45","author":"Guy C","year":"1990","journal-title":"Therapie"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.296.6636.1604-e"},{"key":"e_1_2_6_34_2","first-page":"251","volume":"106","author":"Hawkins T","year":"1993","journal-title":"N. 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