title: Simple non-ion-paired high-performance liquid chromatographic method for simultaneous quantitation of carboxylate and lactone forms of 14 new camptothecin derivatives.
abstract: SN-38 (7-ethyl-10-hydroxycamptothecin) is an active metabolite derived from the semi-synthetic compound camptothecin (CPT) named Irinotecan (CPT-11). The antitumor activity of SN-38 is 1000-fold more potent than the parent CPT-11. Fourteen new derivatives of camptothecin have recently been developed by Yakult Honsha (Tokyo, Japan). Here we describe a simple and cost-effective high-performance liquid chromatography (HPLC) method without an ion-pairing agent, which allows the simultaneous determination of both lactone and carboxylate forms of SN-38 and other camptothecin derivatives. A weak linear relationship between the HPLC retention factors (ln k') and the cellular concentrations of these compounds was observed. These results suggest that low-polarity compounds easily accumulate in cancer cells and may circumvent drug resistance. The HPLC analysis herein described is expected to greatly assist in derivative synthesis and chemical modification of camptothecin-based antitumor drugs.
authors.affiliation: Department of Drug Metabolism and Disposition, Meiji Pharmaceutical University, 204-8588 Tokyo, Japan. ksano@my-pharm.ac.jp
authors.forename: Kazumi
authors.initials: K
authors.lastname: Sano
authors.forename: Megumi
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Shinya
authors.initials: S
authors.lastname: Hayasaka
authors.forename: Kurita
authors.initials: K
authors.lastname: Satake
authors.forename: Yoji
authors.initials: Y
authors.lastname: Ikegami
authors.forename: Hisahiro
authors.initials: H
authors.lastname: Yoshida
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Seigo
authors.initials: S
authors.lastname: Sawada
authors.forename: Shinzo
authors.initials: S
authors.lastname: Tanabe
mesh_terms: D002166:Camptothecin / Q000737:chemistry / Q000302:isolation & purification*; D002264:Carboxylic Acids / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D007783:Lactones / Q000032:analysis*; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence
chemical_list: D002264:Carboxylic Acids; D007783:Lactones; D002166:Camptothecin