Analysis of Zolpidem in Postmortem Fluids and Tissues Using Ultra-Performance Liquid Chromatography-Mass Spectrometry
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2014-02-01
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Abstract: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.
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Main Document Checksum:urn:sha256:b4a322f58b2adf5ac00f0268263ae488c18042da5680c85e9368851f4a09b64b