ArticleForensic toxicology2022
Qualitative analysis of 7- and 8-hydroxyzolpidem and discovery of novel zolpidem metabolites in postmortem urine using liquid chromatography-tandem mass spectrometry.
Article in Forensic toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 5 citations in OpenAlex.
- Interpol review of forensic toxicology, 2023-2025.Forensic science international. Synergy · 2026Review
- Greener and whiter analytical method development and validation for determining the presence of zolpidem tartrate infused in apple juice using RP-HPLCRSC advances · 2024Article
- 2-(4-Fluorophenyl)-1ACS chemical neuroscience · 2023Article
- Qualitative analysis of 7- and 8-hydroxyzolpidem and discovery of novel zolpidem metabolites in postmortem urine using liquid chromatography-tandem mass spectrometry.Forensic toxicology · 2022Article
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Authors and funding
4 authors at 2 institutions in 1 country.
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Abstract
purposeZolpidem (ZOL) is a hypnotic sometimes used in drug-facilitated crimes. Understanding ZOL metabolism is important for proving ZOL intake. In this study, we synthesized standards of hydroxyzolpidems with a hydroxy group attached to the pyridine ring and analyzed them to prove their presence in postmortem urine. We also searched for novel ZOL metabolites in the urine sample using liquid chromatography-triple quadrupole mass spectrometry (LC-QqQMS) and liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QqTOFMS).
methods7- and 8-Hydroxyzolpidem (7OHZ and 8OHZ, respectively) were synthesized and analyzed using LC-QqQMS. Retention times were compared between the synthetic standards and extracts of postmortem urine. To search for novel ZOL metabolites, first, the urine extract was analyzed with data-dependent acquisition, and the peaks showing the characteristic fragmentation pattern of ZOL were selected. Second, product ion spectra of these peaks at various collision energies were acquired and fragments that could be used for multiple reaction monitoring (MRM) were chosen. Finally, MRM parameters were optimized using the urine extract. These peaks were also analyzed using LC-QqTOFMS.
resultsThe presence of 7OHZ and 8OHZ in urine was confirmed. The highest peak among hydroxyzolpidems was assigned to 7OHZ. The novel metabolites found were zolpidem dihydrodiol and its glucuronides, cysteine adducts of ZOL and dihydro(hydroxy)zolpidem, and glucuronides of hydroxyzolpidems.
conclusionsThe presence of novel metabolites revealed new metabolic pathways, which involve formation of an epoxide on the pyridine ring as an intermediate.
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