A Validated Stable Isotope Dilution Liquid Chromatography Tandem Mass Spectrometry Assay for the Trace Analysis of Cocaine and Its Major Metabolites in Plasma

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• 作者：Gurkeerat Singh ; Vinod Arora ; P. Thomas Fenn ; Berend Mets ; and Ian A. Blair
• 刊名：Analytical Chemistry
• 出版年：1999
• 出版时间：May 15, 1999
• 年：1999
• 卷：71
• 期：10
• 页码：2021 - 2027
• 全文大小：79K
• 年卷期：v.71,no.10(May 15, 1999)
• ISSN：1520-6882

文摘

A validated method has been developed for the simultaneous quantitation of cocaine and its major metabolites(ecgonine methyl ester, benzoylecgonine, and norcocaine)in rat plasma. The method is based upon the use of stableisotope dilution liquid chromatography/atmospheric pressure chemical ionization/tandem mass spectrometry.Previously reported methods do not have the sensitivityand specificity that can be attained with this method.Plasma samples required no cleanup apart from proteinprecipitation, and no derivatization was required. Selectedreaction monitoring was performed on the transitions ofm/z 200 to m/z 182 (ecgonine methyl ester), m/z 290to m/z 168 (benzoylecgonine), m/z 304 to m/z 182(cocaine), and m/z 290 to m/z 168 (norcocaine). Thestandard curves were linear over the range from 2 ng/mL (benzoylecgonine, cocaine, and norcocaine) or 5 ng/mL (ecgonine methyl ester) to 1000 ng/mL in rat plasma.The lower limit of quantitation (LLQ) for benzoylecgonine,cocaine, and norcocaine was 2 ng/mL, and for ecgoninemethyl ester, the LLQ was 5 ng/mL for plasma. Thissimple, rapid, reliable, and sensitive method of quantitation had excellent accuracy and precision for the fouranalytes. The method was sensitive enough to permit adetailed study of the pharmacokinetics of cocaine and itsmetabolites after administration of a bolus intravenousdose to rats.