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This Article Full Text Full Text (PDF) 065631.Supplemental Data All Versions of this Article: clinchem.2005.065631v1 52/7/1346    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Quintela, O. Articles by Marquet, P. Search for Related Content PubMed PubMed Citation Articles by Quintela, O. Articles by Marquet, P. Related Collections General Clinical Chemistry Drug Monitoring and Toxicology Automation and Analytical Techniques

Liquid Chromatography–Tandem Mass Spectrometry for Detection of Low Concentrations of 21 Benzodiazepines, Metabolites, and Analogs in Urine: Method with Forensic Applications

¹ Department of Pharmacology-Toxicology, Limoges University Hospital, Limoges, France.
² Forensic Toxicology Department, Institute of Legal Medicine, University of Santiago de Compostela, C/San Francisco, Spain.

^aAddress correspondence to this author at: Department of Pharmacology-Toxicology, Limoges University Hospital, 87042 Limoges, France. Fax 33-555-05-61-62; e-mail pierre.marquet{at}unilim.fr.

Background: Commonly used methods for detecting benzodiazepines (BZPs) and BZP-like substances, such as zolpidem and zopiclone, may not detect low concentrations of these drugs. We developed a liquid chromatographic–tandem mass spectrometric method for identifying these drugs and their relevant metabolites.

Methods: We extracted BZPs from urine by solid-phase extraction with a mixed-mode phase (OASIS® HLB cartridges). Chromatographic separation was performed with a Waters XTerra MS C₁₈ [150 x 2.1 mm (i.d.); bead size, 5 µm] reversed-phase column with deuterated analogs of the analytes as internal standards (IS). Detection was performed with a triple-quadruple mass spectrometer that monitored 2 specific transitions per compound in the electrospray, positive-ion selected-reaction monitoring mode. We tested this technique on urine samples from 12 healthy volunteers and 1 forensic sample obtained in a case of alleged drug-facilitated sexual assault.

Results: Chromatographic separation was achieved within 18 min. The linear dynamic ranges extended from 0.02 or 0.1 µg/L (depending on the drug or metabolite) to 50 µg/L. Extraction recovery (range) was 77%–110%. Limits of detection were 0.05 µg/L. No ion suppression was seen except for alprazolam, for which baseline decreased by almost 20%. In the forensic urine sample, the method detected alprazolam (3.5 µg/L) and its characteristic metabolite, -hydroxyalprazolam (0.17 µg/L).

Conclusion: This method measured low concentrations of BZPs and BZP-like substances and might be useful for analyses of urine in suspected drug-facilitated sexual assault cases.

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				F.-L. Sauvage, J.-M. Gaulier, G. Lachatre, and P. Marquet Pitfalls and Prevention Strategies for Liquid Chromatography-Tandem Mass Spectrometry in the Selected Reaction- Monitoring Mode for Drug Analysis Clin. Chem., September 1, 2008; 54(9): 1519 - 1527. [Abstract] [Full Text] [PDF]