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

Abstract

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 0.20 mL/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 1.2 min. The linear calibration curves were obtained in the concentration range of 0.0190–3.80 ng/mL ( r 2 ≥ 0.99) with a lower limit of quantification (LLOQ) of 0.0190 ng/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 0.125 mg palonosetron hydrochloride.