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Determination of Morphine, Fentanyl and Their Metabolites in Small Sample Volumes Using Liquid Chromatography Tandem Mass Spectrometry

NCJ Number
Journal of Analytical Toxicology Volume: 44 Issue: 4 Dated: 2020 Pages: 325-330
Date Published
May 2020
6 pages

Since the United States and many other countries worldwide are currently experiencing a public health crisis due to the abuse of heroin and illicitly manufactured fentanyl, the current project developed a liquid chromatography tandem mass spectrometry (LC–MS-MS)-based method for the detection of morphine, fentanyl, and their metabolites, including morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), normorphine, norfentanyl and deuterated internal standards in limited sample volumes with the limit of detection of 5.0/0.5 ng/mL (morphine, M3G, M6G, normorphine/fentanyl, norfentanyl).


The inter-assay precision (percent CV) was less than 12 percent for all assays, and the inter-assay bias (percentage) was less than 5 percent. The ruggedness of the method, dilution effect, and carryover were also investigated as part of the study. The simultaneous quantification of morphine, fentanyl, and its metabolites with this simple and time- and cost-efficient method could be successfully applied to samples taken for pharmacokinetic evaluation (antemortem and postmortem) after a single dose of morphine or co-administration of morphine with other drugs (e.g., fentanyl) in rats. (publisher abstract modified)

Date Published: May 1, 2020