Determination of ketotifen and its conjugated metabolite in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study.
A sensitive and specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for the investigation of the pharmacokinetics of ketotifen and its major metabolite, ketotifen N-glucuronide, in human plasma. The plasma samples were treated by liquid-liquid extraction and analyzed using LC/MS/MS with an electrospray ionization interface. Diphenhydramine was used as the internal standard. The method had a lower limit of quantitation of 10 pg/mL for ketotifen, which offered increased sensitivity, selectivity and speed of analysis, compared with existing methods. The intra- and inter-day precision were measured to be below 8.2% and accuracy between -2.4% and 3.4% for all QC samples. Incubation of the plasma samples with beta-glucuronidase allowed the quantitation of ketotifen N-glucuronide. This quantitation method was successfully applied to a pharmacokinetic study of ketotifen and its major metabolite after oral administration of 2 mg ketotifen fumarate to 16 healthy volunteers.
Chen
Xiaoyan
X
Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
Zhong
Dafang
D
Liu
Dan
D
Wang
Yingwu
Y
Han
Ying
Y
Gu
Jingkai
J
D000328:Adult; D002138:Calibration; D002853:Chromatography, Liquid; D020719:Glucuronides / Q000097:blood; D006634:Histamine H1 Antagonists / Q000097:blood* / Q000493:pharmacokinetics*; D006801:Humans; D007665:Ketotifen / Q000097:blood* / Q000493:pharmacokinetics*; D008297:Male; D013058:Mass Spectrometry; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization
D020719:Glucuronides; D006634:Histamine H1 Antagonists; D007665:Ketotifen