Analysis of Zolpidem in Postmortem Fluids and Tissues Using Ultra-Performance Liquid Chromatography-Mass Spectrometry

Zolpidem is a nonbenzodiazepine sedative hypnotic drug used for the short-term treatment of insomnia. Its use is common and wide-spread. While quite effective in producing sedation, zolpidem has potentially hazardous side effects when put in the context of complex tasks. Side effects include drowsiness, dizziness, amnesia, nausea, double vision, diminished reflexes, and a lack of coordination. Due to its potentially deleterious effects on aviation safety, it is important for our laboratory to more fully understand its postmortem concentrations and distribution. Therefore, our laboratory has developed a sensitive method to identify and quantitate zolpidem in biological specimens. Furthermore, we have evaluated the distribution of this compound in various postmortem tissues and fluids from 10 fatal aviation accident cases. Each of these cases had a majority of the desired biological tissues and fluids available for analysis (blood, urine, vitreous humor, liver, lung, kidney, spleen, muscle, heart, and brain). This method incorporated a modified acetonitrile crash and shoot extraction and a Waters Xevo TQ-S (MS/MS) with an Acquity UPLC. The linear dynamic range was 0.39 - 800 ng/mL. The extraction efficiencies ranged from 78 - 87%, depending on concentration. Postmortem blood zolpidem concentrations in these 10 cases ranged from 8 - 77 ng/mL. The highest concentrations of zolpidem present in each victim were found in the liver, spleen, lung, and kidney tissues. Distribution coefficients for zolpidem were determined for each of the specimen types analyzed. These coefficients are expressed relative to the blood concentration in each case. This method proved to be simple, accurate, and robust for the identification and quantitation of zolpidem in postmortem fluids and tissues. The original document contains color images.