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

An automated liquid chromatographic/tandem mass spectrometric (LC/MS/MS) me thod is presented for the screening and confirmation of 16 beta-blocking dr ugs 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 prese nce of any beta-blocking drugs using LC/MS with selected ion monitoring. An y compounds tentatively identified as beta-blocking drugs on the basis of t heir LC retention time and protonated molecular ion were then automatedly s ubjected to a second analysis in which the relevant MS/MS product ion mass spectra were acquired. These product ion mass spectra were then automatical ly searched against a 400-substance mass spectral library containing previo usly acquired beta-blocking drugs. The results demonstrated that library se arch of beta-blocking drugs in urine with MS/MS product ion mass spectra wa s more reliable and produced fewer false negatives than library searching w ith mass spectra derived from single-stage quadrupole MS. The limits of ide ntification in the MS/MS product ion scan ranged from 0.02 mg l(-1) for car vedilol to 1.2 mg l(-1) for pindolol, the majority of the values being belo w 0.2 mg l(-1). Copyright (C) 2000 John Wiley & Sons, Ltd.