Urinary Pharmacokinetics of Immediate and Controlled Release Oxycodone and its Phase I and II Metabolites using LC-MS/MS.

Oxycodone is a schedule II semi-synthetic opioid in the United States that is prescribed for its analgesic effects and has a high potential for abuse. Prescriptions for oxycodone vary based on the dosage and formulation, immediate release (IR) and controlled release (CR). Monitoring oxycodone metabolites is beneficial for forensic casework. The limited studies that involve pharmacokinetics of the urinary excretion of oxycodone metabolites leave a knowledge gap regarding the excretion of conjugated and minor metabolites, pharmacokinetic differences by formulation, and the impact of CYP2D6 activity on the metabolism and excretion of oxycodone. The objectives of this study were to compare urinary excretion of phase I and II metabolites by formulation and investigate if ratio changes over time could be used to predict the time of intake. Subjects (n=7) received a single 10 mg IR tablet of Oxycodone Actavis. A few weeks later the same subjects received a single 10 mg CR tablet of Oxycodone Actavis. During each setting, urine was collected at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 9, 10, 12, 14, 24, 48, and 72 h. Urine samples (100 µL) were diluted with 900 µL internal standard mixture and analyzed on an Acquity UPLC® I-class coupled to a Waters Xevo TQD using a previously validated method. The CYP2D6 phenotypes were categorized as poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM), and ultra-rapid metabolizers (UM). Comparisons between IR and CR were performed using two-tailed paired T-test at a significance level of p=0.05. The metabolite ratios showed a general increase over time. Four metabolite to parent ratios were used to predict the time of intake showing that predictions were best at the early time points.