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.
Document Type
Article
Publication Date
2-5-2017
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.jpba.2016.11.024
Funding Information
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).
Related Content
Refer to Web version on PubMed Central for supplementary material.
Repository Citation
Chen, Xiabin; Zheng, Xirong; Ding, Kai; Zhou, Ziyuan; Zhan, Chang-Guo; and Zheng, Fang, "A Quantitative LC-MS/MS Method for Simultaneous Determination of Cocaine and Its Metabolites in Whole Blood" (2017). Molecular Modeling and Biopharmaceutical Center Faculty Publications. 17.
https://uknowledge.uky.edu/mmbc_facpub/17
Supplementary Material
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Pharmacy and Pharmaceutical Sciences Commons, Substance Abuse and Addiction Commons
Notes/Citation Information
Published in Journal of Pharmaceutical and Biomedical Analysis, v. 134, p. 243-251.
© 2016 Elsevier B.V. All rights reserved.
This manuscript version is made available under the CC‐BY‐NC‐ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/.
The document available for download is the author's post-peer-review final draft of the article.