Probe Electrospray Ionization Tandem Mass Spectrometry for the Detection and Quantification of Benzodiazepines.

Autor:	Griffeuille P; Department of Pharmacology and Toxicology, Limoges University Hospital, Limoges ,France ; and., El Balkhi S; Department of Pharmacology and Toxicology, Limoges University Hospital, Limoges ,France ; and., Dulaurent S; Department of Pharmacology and Toxicology, Limoges University Hospital, Limoges ,France ; and., Saint-Marcoux F; Department of Pharmacology and Toxicology, Limoges University Hospital, Limoges ,France ; and.; Department of Toxicology, Faculty of Pharmacy, University of Limoges, Limoges, France .
Jazyk:	angličtina
Zdroj:	Therapeutic drug monitoring [Ther Drug Monit] 2024 Aug 01; Vol. 46 (4), pp. 522-529. Date of Electronic Publication: 2024 Mar 18.
DOI:	10.1097/FTD.0000000000001189
Abstrakt:	Background: Legally prescribed benzodiazepines (BZDs) and designer BZDs are widely misused and must be determined in multiple contexts (eg, overdose, drug-facilitated sexual assaults, or driving under the influence of drugs). This study aimed to develop a method for measuring serum BZD levels using probe electrospray ionization (PESI) mass spectrometry and an isotope dilution approach. Methods: A tandem mass spectrometer equipped with a probe electrospray ionization source in multiple reaction monitoring mode was used. Isotope dilution was applied for quantification using a deuterated internal standard at a fixed concentration for alprazolam, bromazepam, diazepam, nordiazepam, oxazepam, temazepam, zolpidem, and zopiclone. This method included designer BZDs: clonazolam, deschloroetizolam, diclazepam, etizolam, flualprazolam, flubromazepam, flubromazolam, meclonazepam, nifoxipam, and pyrazolam. Sample preparation was done by mixing 10 µL of serum with 500 µL of an ethanol/ammonium formate 0.01 mol/L buffer. Complete validation was performed, and the method was compared with liquid chromatography coupled with mass spectrometry (LC-MS/MS) and immunoassays (IC) by analyzing 40 real samples. Results: The analysis time for identification and quantification of the 18 molecules was 2.5 minutes. This method was fully validated, and the limits of quantification varied from 5 to 50 mcg/L depending on the molecule. In the 40 real samples, 100% of molecules (n = 89) were detected by both LC-MS/MS and PESI-MS/MS, and regression analysis showed excellent agreement between the 2 methods (r 2 = 0.98). On IC, bromazepam and zolpidem were not detected in 2 and 1 cases, respectively. Conclusions: PESI-MS/MS allows serum BZD detection and measurement. Given the isotope dilution approach, a calibration curve was not required, and its performance was similar to that of LC-MS/MS, and its specificity was higher than that of IC. Competing Interests: The authors declare no conflict of interest. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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