title: High-performance liquid chromatographic analysis of the lactone and carboxylate forms of a topoisomerase I inhibitor (the antitumor drug GI147211) in plasma.
abstract: A sensitive reversed-phase high-performance liquid chromatographic method has been developed and validated for the quantitation of the lactone form (GI147211) of a topoisomerase I inhibitor and its carboxylate form (GI190421) from dog plasma. The method consists of two solid-phase extraction methods. The first method, referred to as the lactone-only method, utilizes a diol Bond Elut cartridge to separate the two forms and measures the lactone directly. The second method, referred to as the total method, converts the carboxylate form to the lactone through acidification of the plasma sample. Total lactone is then extracted from the sample using a C18 Bond Elut cartridge. The carboxylate is quantitated indirectly from the difference of the total and lactone-only. The range of the standard curve for the lactone-only method is 0.096-38.5 nM (0.05-20 ng/ml) and for the total method is 0.193-19.3 nM (0.1-10 ng/ml). This is the most sensitive method reported to date for a camptothecin analogue.
authors.affiliation: Drug Metabolism Department, Glaxo Research Institute, Research Triangle Park, NC 27709, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Stafford
authors.forename: R L
authors.initials: RL
authors.lastname: St Claire
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood; D002264:Carboxylic Acids / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D004285:Dogs; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007783:Lactones / Q000097:blood*; D012680:Sensitivity and Specificity; D059004:Topoisomerase I Inhibitors
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D007783:Lactones; D059004:Topoisomerase I Inhibitors; C091719:lurtotecan; D002166:Camptothecin