Journal Article

Sensitive UPLC–MS-MS Assay for 21 Benzodiazepine Drugs and Metabolites, Zolpidem and Zopiclone in Serum or Plasma

Stephanie J. Marin, Mark Roberts, Michelle Wood and Gwendolyn A. McMillin

in Journal of Analytical Toxicology

Volume 36, issue 7, pages 472-476
Published in print September 2012 | ISSN: 0146-4760
Published online July 2012 | e-ISSN: 1945-2403 | DOI: http://dx.doi.org/10.1093/jat/bks059
Sensitive UPLC–MS-MS Assay for 21 Benzodiazepine Drugs and Metabolites, Zolpidem and Zopiclone in Serum or Plasma

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This paper reports an ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS-MS) method to quantitate 21 benzodiazepines, zolpidem and zopiclone in serum and plasma. After liquid–liquid extraction, an Acquity UPLC with a TQ Detector and BEH C18 column was used (Waters, Milford, MA). The injection-to-injection run time was 7.5 min. Forty-eight authentic serum and plasma patient specimens were analyzed and results compared to those obtained using a previously published method. Average r2 values for linearity (1 to 1,000 ng/mL over five days) were all above 0.995, except α-hydroxytriazolam (0.993). Intra-day and inter-day relative standard deviation values were within ±15% and the percent deviation from the expected concentrations were within ±11%. Recovery ranged from 62 to 89%. Matrix effects ranged from –28% to +6%. The limits of detection were 1 ng/mL, except for lorazepam, nordiazepam, oxazepam and temazepam (5 ng/mL). Ion ratios were ±15% for all analytes. For authentic patient specimens (n = 48, 76 positive results), there was excellent correlation between the UPLC–MS-MS results and the previous method. The best least-squares fit had an equation of y = 1.0708x + 1.6521, r2 = 0.9822. This UPLC–MS-MS method is suitable for the quantification of benzodiazepines and hypnotics in serum and plasma, and offers fast, reliable and sensitive results.

Journal Article.  2571 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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