A validated stable isotope dilution liquid chromatography tandem mass spectrometry assay for the trace analysis of cocaine and its major metabolites in plasma

Gurkeerat Singh, Vinod Arora, P. Thomas Fenn, Berend Mets, Ian A. Blair

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 stable isotope dilution liquid chromatography/atmospheric pressure chemical ionization/tandem mass spectrometry. Previously reported methods do not have the sensitivity and specificity that can be attained with this method. Plasma samples required no cleanup apart from protein precipitation, and no derivatization was required. Selected reaction monitoring was performed on the transitions of m/z 200 to m/z 182 (ecgonine methyl ester), m/z 290 to m/z 168 (benzoylecgonine), m/z 304 to m/z 182 (cocaine), and m/z 290 to m/z 168 (norcocaine). The standard 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 ecgonine methyl ester, the LLQ was 5 ng/mL for plasma. This simple, rapid, reliable, and sensitive method of quantitation had excellent accuracy and precision for the four analytes. The method was sensitive enough to permit a detailed study of the pharmacokinetics of cocaine and its metabolites after administration of a bolus intravenous dose to rats.

Original languageEnglish (US)
Pages (from-to)2021-2027
Number of pages7
JournalAnalytical Chemistry
Volume71
Issue number10
DOIs
StatePublished - May 15 1999

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Trace analysis
Liquid chromatography
Metabolites
Cocaine
Isotopes
Dilution
Mass spectrometry
Assays
Plasmas
Rats
Pharmacokinetics
Atmospheric pressure
Ionization
norcocaine
benzoylecgonine
ecgonine methyl ester
Monitoring
Proteins

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry

Cite this

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abstract = "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 stable isotope dilution liquid chromatography/atmospheric pressure chemical ionization/tandem mass spectrometry. Previously reported methods do not have the sensitivity and specificity that can be attained with this method. Plasma samples required no cleanup apart from protein precipitation, and no derivatization was required. Selected reaction monitoring was performed on the transitions of m/z 200 to m/z 182 (ecgonine methyl ester), m/z 290 to m/z 168 (benzoylecgonine), m/z 304 to m/z 182 (cocaine), and m/z 290 to m/z 168 (norcocaine). The standard 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 ecgonine methyl ester, the LLQ was 5 ng/mL for plasma. This simple, rapid, reliable, and sensitive method of quantitation had excellent accuracy and precision for the four analytes. The method was sensitive enough to permit a detailed study of the pharmacokinetics of cocaine and its metabolites after administration of a bolus intravenous dose to rats.",
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A validated stable isotope dilution liquid chromatography tandem mass spectrometry assay for the trace analysis of cocaine and its major metabolites in plasma. / Singh, Gurkeerat; Arora, Vinod; Fenn, P. Thomas; Mets, Berend; Blair, Ian A.

In: Analytical Chemistry, Vol. 71, No. 10, 15.05.1999, p. 2021-2027.

Research output: Contribution to journalArticle

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