Simple non-ion-paired high-performance liquid chromatographic method for simultaneous quantitation of carboxylate and lactone forms of 14 new camptothecin derivatives.

Kazumi Sano; Megumi Yoshikawa; Shinya Hayasaka; Kurita Satake; Yoji Ikegami; Hisahiro Yoshida; Toshihisa Ishikawa; Seigo Sawada; Shinzo Tanabe

doi:10.1016/s1570-0232(03)00485-9

PubMed · 12957166

Simple non-ion-paired high-performance liquid chromatographic method for simultaneous quantitation of carboxylate and lactone forms of 14 new camptothecin derivatives.

Kazumi Sano·Megumi Yoshikawa·Shinya Hayasaka·Kurita Satake·Yoji Ikegami·Hisahiro Yoshida·Toshihisa Ishikawa·Seigo Sawada·Shinzo Tanabe

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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.

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Camptothecin Carboxylic Acids Chromatography, High Pressure Liquid Hydrogen-Ion Concentration Lactones Reproducibility of Results Spectrometry, Fluorescence Journal Article

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Kazumi Sano, Megumi Yoshikawa, Shinya Hayasaka, Kurita Satake, Yoji Ikegami, Hisahiro Yoshida, Toshihisa Ishikawa, Seigo Sawada, Shinzo Tanabe. 2003-09-25. Simple non-ion-paired high-performance liquid chromatographic method for simultaneous quantitation of carboxylate and lactone forms of 14 new camptothecin derivatives.. https://doi.org/10.1016/s1570-0232(03)00485-9

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