Zolpidem and zolpidem phenyl-4-carboxylic acid pharmacokinetics in oral fluid after a single dose.

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. 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. 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. 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. 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.