Pitfalls and Prevention Strategies for Liquid Chromatography-Tandem Mass Spectrometry in the Selected Reaction– Monitoring Mode for Drug Analysis

Sauvage, François‐Ludovic; Gaulier, Jean‐Michel; Lachâtre, Gérard; Marquet, Pierre

doi:10.1373/clinchem.2008.105478

Cited by 97 publications

(44 citation statements)

References 30 publications

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“…Noticeably, the EPI spectrum of quetiapine includes major fragments at m/z 279, 253, 247, and 221. These fragments followed the same fragmentation pathways as those we described for some phenothiazines in a recent paper [18]. Particularly, the loss of 32 amu between the fragments at m/z 279 and 247 corresponds to the loss of S from the cyclic structure.…”

Section: Case 1: Identification Of Trazodone Metabolites In a Forensisupporting

confidence: 64%

General unknown screening procedure for the characterization of human drug metabolites in forensic toxicology: Applications and constraints

Sauvage

Picard

Saint-Marcoux

et al. 2009

J of Separation Science

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LC coupled to single (LC-MS) and tandem (LC-MS/MS) mass spectrometry is recognized as the most powerful analytical tools for metabolic studies in drug discovery. In this article, we describe five cases illustrating the utility of screening xenobiotic metabolites in routine analysis of forensic samples using LC-MS/MS. Analyses were performed using a previously published LC-MS/MS general unknown screening (GUS) procedure developed using a hybrid linear IT-tandem mass spectrometer. In each of the cases presented, the presence of metabolites of xenobiotics was suspected after analyzing urine samples. In two cases, the parent drug was also detected and the metabolites were merely useful to confirm drug intake, but in three other cases, metabolite detection was of actual forensic interest. The presented results indicate that: (i) the GUS procedure developed is useful to detect a large variety of drug metabolites, which would have been hardly detected using targeted methods in the context of clinical or forensic toxicology; (ii) metabolite structure can generally be inferred from their "enhanced" product ion scan spectra; and (iii) structure confirmation can be achieved through in vitro metabolic experiments or through the analysis of urine samples from individuals taking the parent drug.

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Section: Case 1: Identification Of Trazodone Metabolites In a Forensisupporting

confidence: 64%

General unknown screening procedure for the characterization of human drug metabolites in forensic toxicology: Applications and constraints

Sauvage

Picard

Saint-Marcoux

et al. 2009

J of Separation Science

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“…Our assay is based on the specific quantification of CN-dependent dephosphorylation of a synthetic phosphopeptide substrate by LC-MS/MS in MRM mode, a technique widely available in clinical laboratories (17 ). The use of a stable isotopelabeled form of RII peptide, as an internal standard, helps to reduce experimental variation during sample preparation and acquisition.…”

Section: Discussionmentioning

confidence: 99%

Calcineurin Activity Assay Measurement by Liquid Chromatography–Tandem Mass Spectrometry in the Multiple Reaction Monitoring Mode

et al. 2014

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BACKGROUND: Blood concentrations of the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus are currently measured to monitor immunosuppression in transplant patients. The measurement of calcineurin (CN) phosphatase activity has been proposed as a complementary pharmacodynamic approach. However, determining CN activity with current methods is not practical. We developed a new method amenable to routine use.

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“…Ainsi, trois pics supplémentaires importants ont été repérés correspondant pour l'un à une perte d'un groupement méthyle et pour les deux autres à la perte d'un groupement méthyle, plus l'ajout d'un oxygène dans la formule de l'alimé-mazine [32]. L'enrichissement de base de données de référence, par l'ajout de paramètres caractérisant quelques métabolites principaux de xénobiotiques a plusieurs intérêts majeurs [33].…”

Section: Discussionunclassified

Analyse toxicologique avec mesure par « masse exacte ». Caractérisation de métabolites urinaires par couplage UPLC/QTOF : apports et intérêts dans le cadre de la soumission chimique

Humbert¹,

Richeval²

2012

Ann Toxicol Anal

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Résumé -Objectifs :Le métabolisme des médicaments conduit à des composés plus polaires facilitant leur élimi-nation dans les urines. Peu de médicaments sont retrouvés inchangés dans les urines. Souvent pour mettre en évidence une soumission chimique, le toxicologue reçoit du sang et des urines prélevés plusieurs jours voire une semaine après les faits. Plus les faits seront éloignés des prélèvements, plus les chances de mettre en évidence la moindre trace d'une substance s'amenuisent. Le but de ce travail a été de mettre en place un protocole permettant d'obtenir des informations spectrales sur des métabolites de psychotropes excrétés en grande quantité dans les urines. Méthodes : Les urines de patients ayant ingéré massivement un médicament sont analysées par chromatographie liquide couplée à un spectromètre de masse hybride quadripôle-temps de vol (UPLC XEVO G2 QTOF). Le mode MS e réalise une double acquisition simultanée : une à basse énergie d'accélération pour obtenir la masse exacte des composés, la seconde à haute énergie d'accélération pour fragmenter l'ensemble des composés. Les données sont traitées par des logiciels spécialisés dans la recherche et la caractérisation de métabolites (MetaboLynx TM ) et dans l'analyse des fragments de collision (MassFragment). Résultats : Dans les urines d'un patient ayant ingéré massivement du bromazépam, il a été possible de caractériser 3 métabolites majeurs. Lors d'une ingestion massive d'alimémazine, il a été possible de caractériser 5 métabolites majeurs. Conclusion : L'élargissement de la fenêtre de détection d'un composé dans des urines est possible par la caractérisation des métabolites. Mots clés : Soumission chimique, métabolites, masse exacteAbstract -Objective: The metabolism of drugs leads to more polar compounds, facilitating urinary elimination. Few drugs are recovered unchanged in the urine. Often, to highlight a chemical submission, the toxicologist receives blood and urine for events dating back to several days to a week. If the time between the events and the biological sample is long, the chance of highlighting a product is small. The aim of this study was to establish a protocol to obtain spectral information on metabolites of psychoactive drugs excreted in large quantities in the urine. Methods: The urines of patients who ingested a massive amount of a drug are analyzed by liquid chromatography-hybrid quadrupole timeof-flight mass spectrometry (UPLC QTOF XEVO G2). The MS e mode performs a double simultaneous acquisition: a low-energy acceleration to obtain the exact mass of compounds, the second at high acceleration energy to fragment all of the compounds. The data are processed by specialized software for research and characterization of metabolites (MetaboLynx TM ), and analysis of collision fragments (MassFragment). Results: In the urine of a patient who ingested a massive amount of bromazepam, it was possible to characterize three major metabolites. Also, after a massive ingestion of alimemazine it was possible to characterize five major metab...

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Pitfalls and Prevention Strategies for Liquid Chromatography-Tandem Mass Spectrometry in the Selected Reaction– Monitoring Mode for Drug Analysis

Cited by 97 publications

References 30 publications

General unknown screening procedure for the characterization of human drug metabolites in forensic toxicology: Applications and constraints

General unknown screening procedure for the characterization of human drug metabolites in forensic toxicology: Applications and constraints

Calcineurin Activity Assay Measurement by Liquid Chromatography–Tandem Mass Spectrometry in the Multiple Reaction Monitoring Mode

Analyse toxicologique avec mesure par « masse exacte ». Caractérisation de métabolites urinaires par couplage UPLC/QTOF : apports et intérêts dans le cadre de la soumission chimique

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