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

31 Scopus citations


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
StatePublished - Feb 5 2017

Bibliographical note

Publisher Copyright:
© 2016 Elsevier B.V.


  • 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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