title: 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-C(18) 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 3200 Qtrap mass spectrometry. The method has a chromatographic run time of 5.5 min and is linear within the concentration range 0.01-5.00 ng/mL for plasma and 0.10-30.00 ng/mL for urine both with a LOD of 0.003 ng/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 168 h 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.
authors.affiliation: Pharmacy Department of the Second Artillery General Hospital PLA, Beijing 100088, PR China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Weihang
authors.initials: W
authors.lastname: Tong
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Cheng
authors.initials: C
authors.lastname: Wu
authors.forename: Lihong
authors.initials: L
authors.lastname: Liu
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D016018:Least-Squares Analysis; D008297:Male; D000077924:Palonosetron; D011812:Quinuclidines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D007546:Isoquinolines; D011812:Quinuclidines; D000077924:Palonosetron