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 50°C for 16 h) and liver microsomes (HLMs). Liquid-liquid extraction was followed by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. The calibration range was 0.2-250 ng/mL for plasma and HLM and 10-5000 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 freeze-thaw stability in plasma up to three cycles. In 24-h hydrolyzed urine from subjects administered intranasal oxycodone (30 mg/70 kg, n 5 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.
|Number of pages||8|
|Journal||Journal of Analytical Toxicology|
|State||Published - Jul 2013|
Bibliographical noteFunding Information:
This work was supported in part by grants, a contract and a career development award from the National Institute on Drug Abuse, National Institutes of Health: R01 DA010100 (D.E.M.), R01 DA016718 (S.L.W.), N01-DA-9–7767 (D.E.M.) and K12 DA14040 (M.R.L.), and a grant from the National Institute of Justice 2011: DN-BX-K532 (D.E.M.).
ASJC Scopus subject areas
- Analytical Chemistry
- Environmental Chemistry
- Health, Toxicology and Mutagenesis
- Chemical Health and Safety