Zolpidem and Zolpidem Phenyl‐4‐carboxylic Acid Pharmacokinetics in Oral Fluid after a Single Dose

BACKGROUND: Oral fluid zolpidem detection in the settings of drug-facilitated crime and roadside drug testing indicates recent zolpidem intake. Zolpidem pharmacokinetics in classical biological matrices such as blood and urine have been described; however, reports of such data based on oral fluids are limited. OBJECTIVE: The aim of this study is to describe the pharmacokinetics of zolpidem and its major metabolite zolpidem phenyl-4-carboxylic acid (ZPCA) in oral fluids after intake. METHODS: Ten milligrams of zolpidem tartrate tablets were orally administered to 14 volunteers, and oral fluid samples were collected at various times up to 72 hours and analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) with post-column reagent addition. RESULTS: Both zolpidem and ZPCA could be detected in oral fluid after 1 hour and were rapidly eliminated, with half-lives of 2.77 ± 0.71 hours and 5.11 ± 0.67 hours, respectively. Maximum zolpidem concentrations (36.73 ± 10.89 ng/mL) occurred at 2 ± 0.52 hours, and maximum ZPCA concentrations (0.28 ± 0.16 ng/mL) occurred at 2 ± 0.37 hours. Zolpidem/ZPCA ratios decreased after zolpidem intake, an observation that might be helpful for determining the time of drug use. CONCLUSION: The results showed that the measurement of zolpidem in oral fluid can be used for the non-invasive monitoring of zolpidem consumption and misuse in drug-facilitated crime and roadside drug testing settings.