Liquid chromatography–electrospray quadrupole linear ion trap mass spectrometry method for the quantitation of palonosetron in human plasma and urine: Application to a pharmacokinetic study

Abstract: The new analytical method for the determination of palonosetron in human plasma and urine has been developed based on liquid chromatography–mass spectrometry. The method utilized tramadol as the internal standard (IS). Separation was carried out on a Zorbax Eclipse TC-C18 column using methanol–1mM ammonium formate in water (containing 0.1% formic acid, v/v, pH=2.8) as mobile phase for gradient elution. Detection is carried out by multiple reaction monitoring (MRM) on 3200Qtrap™ mass spectrometry. The method has a chromatographic run time of 5.5min and is linear within the concentration range 0.01–5.00ng/mL for plasma and 0.10–30.00ng/mL for urine both with a LOD of 0.003ng/mL. Intra- and inter-day RSD of the concentration was 3.66–6.60%, 1.29–7.71% for plasma and 2.39–5.76%, 2.06–7.13% for urine. The relative error (RE) was −4.58% to 3.26% for plasma and −1.47% to 2.53% for urine. The recovery rates of palonosetron and IS both for plasma and urine were more than 90%. Palonosetron was stable under all the conditions tested. The method was successfully used to analyze palonosetron in human plasma and urine over a period of 168h after intravenously pumping a single dose of 0.25mg to volunteers. No significant differences were found between the pharmacokinetic parameters and urine accumulated excretory rate for male and female volunteers (P >0.05). A two-compartment model was obtained after administrations. Palonosetron was eliminated at a slow rate in volunteers. The mean urine accumulated excretory rate was 25.97±12.87%. Inter-individual differences could not be neglected due to the high coefficient of variety in several pharmacokinetic parameters and the urine accumulated excretion. [Copyright &y& Elsevier]