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

• Published in: Journal of separation science 2009-09, Vol.32 (18), p.3074-3083
• Main Authors: Sauvage, François-Ludovic, Picard, Nicolas, Saint-Marcoux, Franck, Gaulier, Jean-Michel, Lachâtre, Gérard, Marquet, Pierre
• Format: Article
• Language: English
• Subjects: Analysis; Biological and medical sciences; Chromatography, High Pressure Liquid; Dibenzothiazepines - metabolism; Dibenzothiazepines - urine; Drug Discovery; Forensic Toxicology; General aspects. Methods; General pharmacology; Humans; Medical sciences; Metabolism; Noscapine - metabolism; Noscapine - urine; Oxazines - metabolism; Oxazines - urine; Pharmacology. Drug treatments; Prazepam - metabolism; Prazepam - urine; Quetiapine Fumarate; Reproducibility of Results; Screening; Sensitivity and Specificity; Tandem Mass Spectrometry; Toxicology; Trazodone - metabolism; Trazodone - urine
• ISSN: 1615-9306; 1615-9314
• DOI: 10.1002/jssc.200900092

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.