Simultaneous determination of rupatadine and its metabolite desloratadine in human plasma by a sensitive LC–MS/MS method: Application to the pharmacokinetic study in healthy Chinese volunteers

A sensitive liquid chromatography/tandem mass spectrometry (LC–MS/MS) method was developed for simultaneous determination of rupatadine and its metabolite desloratadine in human plasma. After the addition of diphenhydramine, the internal standard (IS), plasma samples were extracted with a mixture of methyl tert-butyl ether and n-hexane (1:1, v/v). The analysis was performed on a Ultimate™ AQ-C18 (4.6 mm × 100 mm, 5 μm) column using a mobile phase consisting of a 80/20 mixture of methanol/water containing 0.0005% formic acid pumped at 0.3 ml min−1. The analytes and the IS were detected in positive ionization mode and monitoring their precursor → product ion combinations of m/z 416 → 309, 311 → 259, and 256 → 167, respectively, in multiple reaction monitoring mode. The linear ranges of the assay were 0.1–50 and 0.1–20 ng ml−1 for rupatadine and desloratadine, respectively. The lower limits of reliable quantification for both rupatadine and desloratadine were 0.1 ng ml−1, which offered high sensitivity and selectivity. The within- and between-run precision was less than 7.2%. The accuracy ranged from −9.2% to +6.4% and −7.2% to +7.2% for rupatadine and desloratadine in quality control samples at three levels, respectively. The method has been successfully applied to a pharmacokinetic study of rupatadine and its major metabolite after oral administration of 10, 20 and 40 mg rupatadine tablets to healthy Chinese volunteers.