Affordable Access

Publisher Website

Quantification of topotecan by liquid chromatography–mass spectrometry (LC–MS). Application to intestinal transport using rat everted gut sacs

Authors
Journal
Journal of Chromatography B
1570-0232
Publisher
Elsevier
Publication Date
Volume
878
Identifiers
DOI: 10.1016/j.jchromb.2010.01.019
Keywords
  • Topotecan
  • Ondansetron
  • Lc–Ms
  • Everted Gut Sacs
  • Keto-Enol Tautomerism
Disciplines
  • Biology
  • Chemistry

Abstract

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.

There are no comments yet on this publication. Be the first to share your thoughts.