A rapid and accurate UPLC/MS/MS method for the simultaneous determination of zolpidem and its main metabolites in biological fluids and its application in a forensic context

Shi, Yan; Xiang, Ping; Shen, Biao; Shen, Min

doi:10.1016/j.jchromb.2012.10.018

Cited by 20 publications

(21 citation statements)

References 24 publications

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“…The calculated elimination half‐lives ( t 1/2 ) for zolpidem and ZPCA measured in the present study were 2.77 ± 0.71 hours and 5.11 ± 0.67 hour, respectively (a ratio of 0.54); these values appear congruent with the data proposed by Shi et al who observed values of 3.23 ± 0.39 hours and 5.63 ± 0.21 hours, respectively (a ratio of 0.57). The data are in agreement with the t 1/2 of 2.3~2.8 hours reported by Greenblatt et al in a study of zolpidem blood pharmacokinetics.…”

Section: Resultssupporting

confidence: 92%

“…However, the difference may lead to the conclusion that pharmacokinetics are different in the Caucasian and Chinese Han population because of the different metabolic profile of zolpidem. The same inconsistency corresponds to a previous study described by Shi et al for a lower blood C max of zolpidem in Chinese Han population than Caucasian population, calling into question the racial factors when considering the zolpidem metabolism.…”

Section: Resultssupporting

confidence: 81%

“…The rapid metabolism of zolpidem by the liver rapidly converts it to inactive polar metabolites, probably accounting for the shorter t 1/2 of zolpidem and the rapid clearance from the oral cavity due to mouth rinsing and the partial swallowing of the OF, which is highly enriched with the substance (Table ). Significantly lower AUC 0‐∞ values for zolpidem and ZPCA were found in oral fluid than in blood . This finding indicates rapid absorption of zolpidem into the blood and less exposure to zolpidem in the oral fluid immediately after oral administration.…”

Section: Resultsmentioning

confidence: 87%

“…The results showed that zolpidem was detectable until 36 hours after drug intake with the exception of two subjects while ZPCA was not detected after intervals longer than 9 hours with the exception of two subjects. Zolpidem can be detected in the blood as long as 16 hours after administration, and the detection window for this drug in blood is shorter than that in oral fluid. Consequently, the longer monitoring of zolpidem in this study may be due to the lower cut‐off with the help of post‐column addition of reagent.…”

Section: Resultsmentioning

confidence: 99%

“…No previously published study has investigated the windows of detection for ZPCA in oral fluid. In urine samples, the determination of ZPCA when zolpidem is undetectable has been shown to prolong the window of detection for zolpidem ingestion, especially in DFC cases . The detection window of ZPCA may be several days; hence the detection of zolpidem or ZPCA in urine from a DFC victim could stem from a previous zolpidem intake with no relevant to the incident.…”

Section: Resultsmentioning

confidence: 99%

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

Feng¹,

Chen

Xiang

et al. 2019

Drug Testing and Analysis

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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.

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Section: Resultssupporting

confidence: 92%

Section: Resultssupporting

confidence: 81%

Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Feng¹,

Chen

Xiang

et al. 2019

Drug Testing and Analysis

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Long-term follow-up analysis of zolpidem in fingernails after a single oral dose

2013

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The determination of xenobiotics in keratinized matrices, such as nails and hair, has received considerable attention because of the relatively long detection window for compounds. The distribution of xenobiotics in fingernails, unlike hair, was equivocal. The main aim of this study was to use follow-up surveys to measure zolpidem profiles in nails after subjects consumed a single dose of the drug. In addition, the zolpidem concentrations in nails were compared with data for different biosamples, such as hair and blood from previous work. With these preconditions, a high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of zolpidem in nails. Nails underwent alkaline hydrolysis and were extracted with diethyl ether. A Capcell Pak C18 MGII column was used to separate the target compound, and an API 4000 Qtrap mass spectrometer was used as a detector. The results for nail samples from seven subjects who had taken a single 10 mg zolpidem dose were significant: two relatively high zolpidem concentrations were observed in the long-term follow-up analysis of nails. The zolpidem concentration was less than 1.74 pg/mg and less than 3.29 pg/mg in fingernails and toenails, respectively. The subsequent peak concentration of zolpidem was observed between 10 and 15 weeks after each subject took a single dose of the drug. This result suggested that the germinal matrix area was a primary in vivo pathway for zolpidem secretion into the nail. The analysis of biosamples, such as nails, may be a useful adjunct to conventional methods of drug testing and hair analysis. Further research is needed concerning the contamination risk in analysis of nail biosamples.

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A comprehensive and sensitive method for hair analysis in drug-facilitated crimes and incorporation of zolazepam and tiletamine into hair after a single exposure

et al. 2015

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Hair is a highly relevant specimen that is used to verify drug exposure in victims of drug-facilitated crime (DFC) cases. In the present study, a new analytical method involving ultrahigh-performance liquid chromatography-tandem mass spectrometry was developed for determining the presence of model drugs, including zolazepam and tiletamine and their metabolites in hair specimens from DFCs. The incorporation of zolazepam and tiletamine into hair after a single exposure was investigated in Long-Evans rats with the ratio of the hair concentration to the area under the curve. For rapid and simple sample preparation, methanol extraction and protein precipitation were performed for hair and plasma, respectively. No interference was observed in drug-free hair or plasma, except for hair-derived diphenhydramine in blank hair. The coefficients of variance of the matrix effects were below 12%, and the recoveries of the analytes exceeded 70% in all of the matrices. The precision and accuracy results were satisfactory. The limits of quantification ranged from 20 to 50 pg in 10 mg of hair. The drug incorporation rates were 0.03 ± 0.01% for zolazepam and 2.09 ± 0.51% for tiletamine in pigmented hair. We applied the present method to real hair samples in order to determine the drug that was used in seven cases. These results suggest that this comprehensive and sensitive hair analysis method can successfully verify a drug after a single exposure in crimes and can be applied in forensic and clinical toxicology laboratories.

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A rapid and accurate UPLC/MS/MS method for the simultaneous determination of zolpidem and its main metabolites in biological fluids and its application in a forensic context

Cited by 20 publications

References 24 publications

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

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

Long-term follow-up analysis of zolpidem in fingernails after a single oral dose

A comprehensive and sensitive method for hair analysis in drug-facilitated crimes and incorporation of zolazepam and tiletamine into hair after a single exposure

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