We describe a liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for levocetirizine quantification (I) in human plasma. Sample preparation was made using a fexofenadine (H) addition as internal standard (IS), liquid-liquid extraction using cold dichloromethane, and dissolving the final extract in acetonitrile. I and II (IS) were injected in a C18 column and the mobile phase composed of acetonitrile:water:formic acid (80.00:19.90:0.10, v/v/v) and monitored using positive electrospray source with tandem mass spectrometry analyses. The selected reaction monitoring (SRM) was set using precursor ion and product ion combinations of m/z 389 > 201 forI and m/z 502 > 467 for II. The limit of quantification and the dynamic range achieved were 0.5 ng/mL and 0.5-500.0 ng/mL. Validation results on linearity, specificity, accuracy, precision and stability, as well as its application to the analysis of plasma samples taken up to 48 h after oral administration of 5 mg of levocetirizine dichloridrate in healthy volunteers demonstrate its applicability to bioavailability studies. (c) 2007 Elsevier B.V. All rights reserved.86241671132139