Journal
JOURNAL OF ANALYTICAL TOXICOLOGY
Volume 37, Issue 6, Pages 337-344Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/jat/bkt042
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Funding
- National Institute on Drug Abuse, National Institutes of Health [R01 DA010100, R01 DA016718, N01-DA-9-7767, K12 DA14040]
- National Institute of Justice [DN-BX-K532]
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The opioid analgesic oxycodone is widely abused and increasingly associated with overdose deaths. A sensitive analytical method was developed for oxycodone and its metabolites, noroxycodone and oxymorphone, in human plasma, urine (enzymatic hydrolysis at 50C for 16 h) and liver microsomes (HLMs). Liquidliquid extraction was followed by high-performance liquid chromatographyelectrospray ionization-tandem mass spectrometry. The calibration range was 0.2250 ng/mL for plasma and HLM and 105000 ng/mL for urine. Intra- and interrun accuracies were within 13.3 of target; precisions were within 12.8 for all matrices. Recoveries from plasma were: oxycodone, 75.6; noroxycodone, 37.4 and oxymorphone, 18.2. Analytes exhibited room temperature stability in plasma and urine up to 24 h, and freezethaw stability in plasma up to three cycles. In 24-h hydrolyzed urine from subjects administered intranasal oxycodone (30 mg/70 kg, n 5), mean concentrations (ng/mL) and daily doses excreted were: oxycodone, 1150, 6.53; noroxycodone, 1330, 7.81 and oxymorphone, 3000, 17.1. Oxycodone incubated with HLM produced more noroxycodone than oxymorphone. With a panel of recombinant human cytochrome P450s (CYPs), CYP2C18 and CYP3A4 produced the most noroxycodone, whereas CYP2D6 produced the most oxymorphone. These results demonstrate a new method suitable for both in vivo and in vitro metabolism and pharmacokinetic studies of oxycodone.
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