A quantitative LC–MS/MS method for simultaneous determination of cocaine and its metabolites in whole blood

Xiabin Chen, Xirong Zheng, Kai Ding, Ziyuan Zhou, Chang Guo Zhan, Fang Zheng

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

As new metabolic pathways of cocaine were recently identified, a high performance liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed to simultaneously determine cocaine and nine cocaine-related metabolites in whole blood samples. One-step solid phase extraction was used to extract all of the ten compounds and corresponding internal standards from blood samples. All compounds and internal standards extracted were separated on an Atlantis T3 (100 Å, 3 μm, 2.1 mm × 150 mm I.D) column and detected in positive ion and high sensitivity mode with multiple reaction monitoring. This method was validated for its sensitivity, linearity, specificity, accuracy, precision, recovery, and stability. All of the ten compounds were quantifiable ranging from the lower limit of quantification (LLOQs) of ∼10 nM (1.9–3.2 ng/ml) to ∼1000 nM (190–320 ng/ml) without any interfering substance. Accuracy and precision were determined, and both of them were within the acceptance criteria of the United States (US) Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. The recovery was above 66.7% for all compounds. Stability tests demonstrated the stability of compounds under different storage conditions in whole blood samples. The method was successfully applied to a pharmacokinetic study with co-administration of cocaine and alcohol in rats.

Original languageEnglish
Pages (from-to)243-251
Number of pages9
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume134
DOIs
StatePublished - Feb 5 2017

Bibliographical note

Publisher Copyright:
© 2016 Elsevier B.V.

Funding

This work was supported by the National Institutes of Health (NIH) through an Avant-Garde Award ( UH2 DA041115 ) and R01 grants ( R01 DA035552 , R01 DA032910 , R01 DA013930 , and R01 DA025100 ). The authors gratefully acknowledge helpful discussions with Dr. Markos Leggas and Ms. Jamie Horn.

FundersFunder number
National Institutes of Health (NIH)R01 DA035552, R01 DA013930, UH2 DA041115, R01 DA025100
National Institutes of Health (NIH)
Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug AbuseR01DA032910
Author National Institute on Drug Abuse DA031791 Mark J Ferris National Institute on Drug Abuse DA006634 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA026117 Mark J Ferris National Institute on Alcohol Abuse and Alcoholism AA028162 Elizabeth G Pitts National Institute of General Medical Sciences GM102773 Elizabeth G Pitts Peter McManus Charitable Trust Mark J Ferris National Institute on Drug Abuse

    Keywords

    • Alcohol
    • Cocaine
    • Drug metabolism
    • LC–MS/MS
    • SPE

    ASJC Scopus subject areas

    • Analytical Chemistry
    • Pharmaceutical Science
    • Drug Discovery
    • Spectroscopy
    • Clinical Biochemistry

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