Quantification of topotecan by liquid chromatography–mass spectrometry (LC–MS). Application to intestinal transport using rat everted gut sacs |
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Authors: | Cécile Arellano Peggy Gandia Laure Bettuing John Woodley Etienne Chatelut |
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Institution: | 1. Faculté des Sciences Pharmaceutiques, Université Paul Sabatier Toulouse 3, 31062 Toulouse, France;2. Laboratoire de Pharmacocinétique et Toxicologie Clinique, Institut Fédératif de Biologie, Hôpital Purpan, 31059 Toulouse, France;3. EA3035 Clinique et Expérimentale de Médicaments Anticancereux, Institut Claudius Regaud, 31052 Toulouse, France |
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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. |
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