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  • Title: Determination of ketotifen and its conjugated metabolite in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study.
    Author: Chen X, Zhong D, Liu D, Wang Y, Han Y, Gu J.
    Journal: Rapid Commun Mass Spectrom; 2003; 17(22):2459-63. PubMed ID: 14608613.
    Abstract:
    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.
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