Rapid determination of granisetron in human plasma by liquid chromatography coupled to tandem mass spectrometry and its application to bioequivalence study.
A simple, sensitive and rapid method for analysis of granisetron in human plasma, utilizing liquid chromatography tandem mass spectrometry (LC-MS/MS), has been developed and validated to satisfy FDA guidelines for bioanalytical methods. The analyte and internal standard (IS) were isolated from 100microl plasma samples by liquid-liquid extraction (LLE). A Varian 1200l tandem mass spectrometer equipped with an electrospray ionization source was operated in selected reaction monitoring (SRM) mode with the precursor-to-product ion transitions m/z 313.4/138 for granisetron and m/z 270/201 for the IS used for quantitation. The assay exhibited a linear dynamic range of 0.02-20ng/ml for granisetron in human plasma. The lower limit of quantification (LLOQ) was 0.02ng/ml with a relative standard deviation of less than 15%. The mean extraction recovery from spiked plasma samples was 97.9%. The intra-day accuracy of the assay was within 10% of nominal and intra-day precision was better than 15% C.V. A run time of 2.0min for each sample made it possible for high-throughput bioanalysis. The method was employed in a bioequivalence study of two formulations of granisetron hydrochloride 1mg rapidly disintegrating tablets/1mg capsules.
Jiang
Yunyun
Y
Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China.
Lin
Mei
M
Fan
Guorong
G
Chen
Yi
Y
Li
Zhen
Z
Zhao
Weiquan
W
Wu
Yutian
Y
Hu
Jinhong
J
D000284:Administration, Oral; D000328:Adult; D044466:Asian People; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D018592:Cross-Over Studies; D017829:Granisetron / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D015203:Reproducibility of Results; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016037:Single-Blind Method; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013607:Tablets; D013810:Therapeutic Equivalency
D017829:Granisetron; D012702:Serotonin Antagonists; D013607:Tablets