Simultaneous screening and quantitation of 18 antihistamine drugs in bloodby liquid chromatography ionspray tandem mass spectrometry

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is prese nted for the simultaneous screening and quantitation of 18 antihistamine dr ugs in blood samples. Sample pretreatment involved liquid-liquid extraction of the basic antihistamines followed by a second extraction of the acidic antihistamines. The recoveries were 43-113% for basic drugs and 23-66% for acidic drugs. The combined extracts were run by LC on C-18 reversed phase c olumn using acetonitrile-ammonium acetate mobile phase at pH 3.2. The mass spectrometric analysis was performed with a triple stage quadrupole mass an alyzer. Screening was performed using Multiple reaction monitoring (MRM) an d any compounds tentatively identified as, antihistamine drugs were then au tomatedly verified by their Product Ion Spectra in a subsequent MS/MS run. Quantitation was based on the MRM data from the screening step. In validati on tests, the method showed good linearity at the relevant concentrations. The attained limits of quantitation varied between 0.0005 and 0.01 mg/l in blood and were lower than the therapeutic concentrations (C-max). The limit s for identification by Product Ion Spectra were also lower than C-max, exc ept for clemastine, which has exceptionally low concentrations in blood. Th e intra-assay relative standard deviations were better than 10% and the ina ccuracy varied between 39% for levocabastine and 5% for cyclizine, the majo rity of the values being <20%. (C) 2001 Elsevier Science Ireland Ltd. All r ights reserved.