Automated liquid chromatographic/tandem mass spectrometric method for screening beta-blocking drugs in urine.
An automated liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method is presented for the screening and confirmation of 16 beta-blocking drugs in clinical and autopsy urine samples. The described method involved C(18) 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 beta-blocking drugs using LC/MS with selected ion monitoring. Any compounds tentatively identified as beta-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 beta-blocking drugs. The results demonstrated that library search of beta-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).
Department of Forensic Medicine, University of Helsinki, Finland. merja.gergov@helsinki.fi
M
M
Gergov
J N
JN
Robson
E
E
Duchoslav
I
I
Ojanperä
D000319:Adrenergic beta-Antagonists / Q000652:urine*; D001331:Automation; D001344:Autopsy; D002853:Chromatography, Liquid / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D012680:Sensitivity and Specificity; D012984:Software
D000319:Adrenergic beta-Antagonists