Structural analysis of quazepam metabolites in bile by ion trap time-of-flight mass spectrometry

Yamaguchi, Koji; Goda, Takahiro; Yamaki, Shohei; Ohno, Youkichi

doi:10.1016/j.forsciint.2015.07.016

Cited by 3 publications

(4 citation statements)

References 10 publications

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“…In this regard, the laboratory must ensure that the method is robust in its ability to handle the non-ideal specimen. A review of the literature shows that several analytical options exist for preparing a bile sample for instrumental analysis including liquid-liquid extraction (LLE) and solid-phase extraction (SPE) (2, 7, 8). While it is possible to apply methods designed for the detection of drugs in blood directly to bile specimens, due to the potential for interference from drug metabolites concentrated in the specimen, additional sample purification is recommended to ensure appropriate identification of drugs.…”

Section: Discussionmentioning

confidence: 99%

The Utility of Bile in Postmortem Forensic Toxicology

Bierly¹,

Labay²

2018

Academic Forensic Pathology

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Bile is one matrix type that may be collected at autopsy and submitted to the toxicology laboratory for analysis. Because it is an excretion product of the liver, it can be used for screening purposes and to determine what drugs an individual used or was exposed to prior to death. This paper presents collection and analytical considerations of bile, and provides an overview of its utility from a testing and interpretation perspective.

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Section: Discussionmentioning

confidence: 99%

The Utility of Bile in Postmortem Forensic Toxicology

Bierly¹,

Labay²

2018

Academic Forensic Pathology

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“…Novel metabolites can show different characteristics in the time courses of blood concentration, distribution, and excretion, and these findings enable further understanding of drug metabolism. For example, we previously found novel quazepam metabolites in human bile and revealed that some of them accumulate in bile at extremely high concentrations [6].…”

Section: Introductionmentioning

confidence: 99%

Qualitative analysis of 7- and 8-hydroxyzolpidem and discovery of novel zolpidem metabolites in postmortem urine using liquid chromatography–tandem mass spectrometry

et al. 2022

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Purpose Zolpidem (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). Methods 7- 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. Results The 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. Conclusions The 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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“…In this way, target and nontarget analysis can be performed and unknown molecules can be identified. 18,19 In this work, we used ultraperformance liquid chromatography coupled to mass spectrometry−ion trap−time-of-flight (UPLC−MS−IT−TOF) to study the metabolite production of A. ochraceus. Seven circumdatins and their product ions were identified.…”

Section: ■ Introductionmentioning

confidence: 99%

“…TOF instruments are able of acquiring data in a full scan mode throughout a range of mass with mass accuracy in the low parts per million range. In this way, target and nontarget analysis can be performed and unknown molecules can be identified. , …”

Section: Introductionmentioning

confidence: 99%

UPLC–MS–IT–TOF Identification of Circumdatins Produced by Aspergillus ochraceus

González-Jartı́n

Alfonso

Sáinz

et al. 2017

J. Agric. Food Chem.

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A method based on the combined use of ultraperformance liquid chromatography coupled to mass spectrometry-ion trap-time-of-flight (UPLC-MS-IT-TOF) detection was employed to identify the metabolite production of Aspergillus ochraceus, which is the major cause of food and feed contamination due to ochratoxin A. Under the proposed chromatographic conditions, seven metabolites belonging to the family of circumdatins were separated and identified. Their initial identification was performed through the exact molecular formula, as a function of their accurate mass. Collision-induced dissociation was applied to predict precursor and product ions, and the elemental composition of each compound was obtained. The elimination of nitrogenous groups followed by successive losses of carbonyl groups is the common fragmentation pathway of circumdatins. With the fragmentation data obtained, an UPLC-MS/MS method was created and optimized to detect circumdatins in corn samples.

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Structural analysis of quazepam metabolites in bile by ion trap time-of-flight mass spectrometry

Cited by 3 publications

References 10 publications

The Utility of Bile in Postmortem Forensic Toxicology

The Utility of Bile in Postmortem Forensic Toxicology

Qualitative analysis of 7- and 8-hydroxyzolpidem and discovery of novel zolpidem metabolites in postmortem urine using liquid chromatography–tandem mass spectrometry

UPLC–MS–IT–TOF Identification of Circumdatins Produced by Aspergillus ochraceus

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