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Title of article :
Quantification of topotecan by liquid chromatography–mass spectrometry (LC–MS). Application to intestinal transport using rat everted gut sacs
Author/Authors :
Arellano، نويسنده , , Cécile and Gandia، نويسنده , , Peggy and Bettuing، نويسنده , , Laure and Woodley، نويسنده , , John and Chatelut، نويسنده , , Etienne، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2010
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Abstract :
Topetecan is an important anti-cancer drug that has recently become available as an oral formulation. In order to study its intestinal absorption in vitro and a potential drug–drug interaction with the anti-emetic ondansetron, a sensitive and accurate method for the analysis of topotecan in biological media was required. We developed a liquid–liquid extraction method at pH 7.0–7.5 with a recovery of 85% and which took into account the complex chemical behaviour of topotecan related to the lactone opening and the keto-enol tautomerism. This enabled us to validate a new specific and sensitive LC–MS method of analysis, with satisfactory inter- and intra-day repeatability and accuracy. The method was applied to a study of topotecan uptake in rat everted gut sacs that showed that, despite being a P-glycoprotein substrate like topotecan, ondansetron did not interfere with topotecan uptake.
Keywords :
Ondansetron , LC–MS , Topotecan , Everted gut sacs , Keto-enol tautomerism
Journal title :
Journal of Chromatography B
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