Premium
Determination of ketotifen and its conjugated metabolite in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study
Author(s) -
Chen Xiaoyan,
Zhong Dafang,
Liu Dan,
Wang Yingwu,
Han Ying,
Gu Jingkai
Publication year - 2003
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.1189
Subject(s) - chemistry , chromatography , ketotifen , metabolite , glucuronide , liquid chromatography–mass spectrometry , tandem mass spectrometry , pharmacokinetics , mass spectrometry , electrospray ionization , detection limit , pharmacology , biochemistry , medicine , asthma
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 β ‐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. Copyright © 2003 John Wiley & Sons, Ltd.