Urine tapentadol quantification in people injecting supratherapeutic doses: Clinical utility and liquid chromatography-tandem mass spectrometry method validation

Background: Tapentadol, a dual-action opioid, is increasingly misused in India by intravenous injection of crushed tablets. Objective urine testing is scarce, and pharmacokinetic data for injected supratherapeutic use are limited. Aim: To validate a practical liquid chromatography-tandem mass spectrometry (LC-MS/MS) urine assay, estimate optimal detection time-points in clinical settings, and define concentration cut-offs at those time-points. Methods: We interviewed people with injecting Tapentadol use for last-use details (time since use, dose). Multiple urine specimens were collected (May 2023–Feb 2024). LC-MS/MS quantification was validated using UNODC guidelines. Optimal thresholds and maximal accuracy were estimated at prespecified clinically relevant time-points (24, 72, 120, and 168 hours). Results: We analyzed 778 samples from 342 male patients; median age 24 years (IQR 22–26). Median daily Tapentadol dose 1,000 mg (IQR 500–1500); median injection frequency 10/day (IQR 8–15); median last-use-dose 300 mg (IQR 200–500). Urine concentrations declined exponentially over time. Analytical performance: linearity r² > 0.998 (50–1000 ng/mL), negligible carryover, matrix effect ≤10%, and limit of quantification 1 ng/mL. Accuracy was highest at 72 hours with an optimal concentration cut point of 205 ng/mL (sensitivity 1.00, specificity 0.98, and accuracy 0.99). Conclusion: We report a feasible, validated LC-MS/MS urine assay for Tapentadol with good performance at clinically relevant time-points, best performance being at 72 hours after last use. Tapentadol concentration decreased exponentially over time (first-order elimination kinetics), but remained detectable beyond 48 hours, possibly due to saturation kinetics with supratherapeutic-dose IV use or the impact of excipients. These concentration thresholds can support objective monitoring of abstinence/relapse in clinical care.