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Simultaneous quantification of buprenorphine, norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide in human placenta by liquid chromatography mass spectrometry

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Abstract

A LCMS method was developed and validated for the determination of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and norbuprenorphine glucuronide (NBUP-Gluc) in placenta. Quantification was achieved by selected ion monitoring of m/z 468.4 (BUP), 414.3 (NBUP), 644.4 (BUP-Gluc), and 590 (NBUP-Gluc). BUP and NBUP were identified monitoring MS2 fragments m/z 396, 414 and 426 for BUP, and 340, 364 and 382 for NBUP, and glucuronide conjugates monitoring MS3 fragments m/z 396 and 414 for BUP-Gluc, and 340 and 382 for NBUP-Gluc. Linearity was 1–50 ng/g. Intra-day, inter-day and total assay imprecision (% RSD) were <13.4%, and analytical recoveries were 96.2–113.1%. Extraction efficiencies ranged from 40.7–68%, process efficiencies 38.8–70.5%, and matrix effect 1.3–15.4%. Limits of detection were 0.8 ng/g for all compounds. An authentic placenta from an opioid-dependent pregnant woman receiving BUP pharmacotherapy was analyzed. BUP was not detected but metabolite concentrations were NBUP-Gluc 46.6, NBUP 15.7 and BUP-Gluc 3.2 ng/g.

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Acknowledgments

This research was supported by the National Institutes of Health, Intramural Research Program, National Institute on Drug Abuse, and funding for Marta Concheiro, Ph.D. from the Ministerio de Educación y Ciencia of Spain (Grant number EX-2007-1194). The authors would like to thank Drs. Fred Askin, Gerrun March, and Leigh Ruane from Johns Hopkins Bayview Medical Center (Baltimore, MD) for their help in providing placenta samples.

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Authors and Affiliations

  1. Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Biomedical Research Center (BRC), 251 Bayview Boulevard, Suite 200, Room 05A721, Baltimore, MD, 21224, USA

    Marta Concheiro-Guisan, Diaa M. Shakleya & Marilyn A. Huestis

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  1. Marta Concheiro-Guisan
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  2. Diaa M. Shakleya
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  3. Marilyn A. Huestis
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Correspondence to Marilyn A. Huestis.

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Concheiro-Guisan, M., Shakleya, D.M. & Huestis, M.A. Simultaneous quantification of buprenorphine, norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide in human placenta by liquid chromatography mass spectrometry. Anal Bioanal Chem 394, 513–522 (2009). https://doi.org/10.1007/s00216-009-2706-z

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  • DOI: https://doi.org/10.1007/s00216-009-2706-z

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