Determination of palonosetron in human plasma by ultra performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

A rapid, sensitive and selective ultra performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed for the determination of palonosetron (PALO) in human plasma. Verapamil was used as the internal standard (I.S.). Sample pretreatment involved liquid-liquid extraction with diethyl ether under alkaline condition. Chromatographic separation was carried out on an ACQUITY UPLC™ HSS T(3) column with mobile phase consisting of methanol-water containing 0.1% formic acid (80:20, v/v) at a flow-rate of 0.20mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. The ion transitions of PALO and I.S. were m/z 297.3→109.8 and m/z 455.1→164.9, respectively. Each plasma sample was chromatographed within 1.2min. The linear calibration curves were obtained in the concentration range of 0.0190-3.80ng/mL (r(2)≥0.99) with a lower limit of quantification (LLOQ) of 0.0190ng/mL. The intra- and inter-day precision (relative standard deviation, R.S.D.) values were all less than 11% and accuracy (relative error, R.E.) was from 4.3% to 6.1% at all quality control (QC) levels. The method has been successfully applied to determine the plasma concentration of PALO in healthy Chinese volunteers after intravenous administration of a single dose of 0.125mg palonosetron hydrochloride.