Automated liquid chromatographic/tandem mass spectrometric method for screening β-blocking drugs in urine

• Published in: Journal of mass spectrometry. 2000-07, Vol.35 (7), p.912-918
• Main Authors: Gergov, M., Robson, J. N., Duchoslav, E., Ojanperä, I.
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - urine; Analysis; Automation; Autopsy; Biological and medical sciences; Chromatography, Liquid - methods; Drug Evaluation, Preclinical - methods; General pharmacology; Humans; ionspray; liquid chromatography/collision induced dissociation tandem mass spectrometry; liquid chromatography/collision-induced dissociation mass spectrometry; Mass Spectrometry - methods; Medical sciences; Pharmacology. Drug treatments; screening; Sensitivity and Specificity; Software; β-blocking drugs
• ISSN: 1076-5174; 1096-9888
• DOI: 10.1002/1096-9888(200007)35:7<912::AID-JMS19>3.0.CO;2-4

An automated liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method is presented for the screening and confirmation of 16 β‐blocking drugs in clinical and autopsy urine samples. The described method involved C18 solid phase extraction, LC separation and MS analysis on a triple‐stage quadrupole mass analyser. Samples were initially pre‐screened for the presence of any β‐blocking drugs using LC/MS with selected ion monitoring. Any compounds tentatively identified as β‐blocking drugs on the basis of their LC retention time and protonated molecular ion were then automatedly subjected to a second analysis in which the relevant MS/MS product ion mass spectra were acquired. These product ion mass spectra were then automatically searched against a 400‐substance mass spectral library containing previously acquired β‐blocking drugs. The results demonstrated that library search of β‐blocking drugs in urine with MS/MS product ion mass spectra was more reliable and produced fewer false negatives than library searching with mass spectra derived from single‐stage quadrupole MS. The limits of identification in the MS/MS product ion scan ranged from 0.02 mg l−1 for carvedilol to 1.2 mg l−1 for pindolol, the majority of the values being below 0.2 mg l−1. Copyright © 2000 John Wiley & Sons, Ltd.