A rapid liquid chromatographic tandem mass spectrometry (LC-MS/MS) assay for the measurement of loratadine level in human plasma was developed and validated. One ml plasma samples containing loratadine and 0.18 µg of metoclopramide as (internal standard, IS) were extracted with 5 ml tert-butyl methyl ether and reconstituted with 80 µl of acetonitrile. Analysis was performed using a reversed phase Atlantis dC18 column and a mobile phase consisting of 0.4% formic acid and acetonitrile (20:80, v:v) and delivered at a flow rate of 0.25 ml/min. The eluents were monitored using electrospray ionization in the positive ion mode with transition mass to charge ratio (m/z) at 383.4→337.2 and 299.8→226.9 for loratadine and IS, respectively. The retention times of the IS and loratadine were around 1.53 and 2.33 min, respectively. Mean matrix effect was measured as -11.4% for loratadine and -14.4% for the IS. Detection limit of loratadine in plasma was 0.3 ng/ml. The relationship between loratadine concentration in plasma and the peak area ratio of loratadine / IS was linear (R2 ³ 0.9945) in the range of 0.5–100 ng/ml, and the intra- and inter-day coefficient of variations (CV) were ≤ 11.3%. Mean extraction recoveries for loratadine and the IS were 87% and 91% respectively, whereas accuracy (relative recovery) ranged from 99% to 111% quality control samples and from 93% to 105%  using back- calculated concentrations. The method was applied to assess the stability of loratadine under various conditions generally encountered in the clinical laboratory. Stability for processed samples (24 hours at room temperature, 48 hours -20 ºC) and unprocessed samples (24 hours at room temperature, 12 weeks -20 ºC) was ≥ 94%. Key words: Loratadine, Metoclopramide, Human plasma, HPLC