Quantitative Determination of Loratadine in Rat Plasma by LC-MS/MS Method and Its Application in a Bioavailability Study

A sensitive, simple and fast LC-MS/MS method was established and validated for the determination of loratadine in rat plasma. The preparation of plasma sample was completed through a one-step liquid-liquid extraction method. An UHPLC column Phenomenex Kinetex C18 (50 mm x 2.1 mm, 2.6 mu m) was utilized to achieve the chromatography separation. Mobile phases A and B were acetonitrile and water with a ratio of 45:55 (v/v) under an isocratic gradient, both comprising 0.2% formic acid. Multiple reaction monitoring mode (MRM) was carried out on the triple quadrupole detection in position ionization mode with an electrospray ionization source, the transitions of m/z 383.1 -> 337.2 and m/z 284.9 -> 193.3 were used to determine loratadine and diazepam (internal standard), respectively. The total analysis run time was 3.5 min and the elution time of loratadine and diazepam occurred at 1.1 and 2.1 min, respectively. This method has the advantages of higher sensitivity (0.04 ng mL(-1)), wider linear range (0.04-400 ng mL(-1), r(2) > 0.995), shorter analysis time (3.5 min), needing only a smaller plasma volume (50 mu L) and simple preparation process. The accuracy and precision of loratadine in all QC samples met the requirements. This novel method was successfully applied to a bioavailability research of loratadine nanosuspensions in rats.