大鼠血浆中抗肿瘤药物喜树碱及其内酯环开环形式的高效液相色谱分析

High-performance liquid chromatographic analysis of the antitumour drug camptothecin and its lactone ring-opened form in rat plasma.

作者信息

Beijnen J H, Rosing H, ten Bokkel Huinink W W, Pinedo H M

机构信息

Slotervaart Hospital, Amsterdam, Netherlands.

出版信息

J Chromatogr. 1993 Jul 23;617(1):111-7. doi: 10.1016/0378-4347(93)80428-7.

DOI:10.1016/0378-4347(93)80428-7

PMID:8376523

Abstract

A sensitive high-performance liquid chromatographic (HPLC) method is described for the simultaneous determination of the antitumour drug camptothecin (I) and its lactone ring-opened form (II) in plasma. The sample pretreatment involved protein precipitation with cold methanol (-30 degrees C). The methanolic extract was injected directly onto the HPLC column. Chromatography was carried out with a LiChrosorb RP-18 column (particle size 5 microns) and a mobile phase composed of methanol-phosphate buffer (5 mM, pH 6.5)-0.3 M tetrabutylammonium phosphate solution (500:500:15, v/v/v). The column effluent was monitored spectrofluorimetrically with the excitation wavelength set at 369 nm and the emission wavelength at 426 nm. The chemical stabilities of camptothecin and the ring-opened form in aqueous solutions, in plasma and after methanolic extraction, were investigated. The proposed method was validated and utilized in pharmacokinetic studies with rats.

摘要

描述了一种灵敏的高效液相色谱（HPLC）方法，用于同时测定血浆中的抗肿瘤药物喜树碱（I）及其内酯环开环形式（II）。样品预处理包括用冷甲醇（-30℃）进行蛋白沉淀。将甲醇提取物直接注入HPLC柱。使用LiChrosorb RP - 18柱（粒径5微米）进行色谱分析，流动相由甲醇 - 磷酸盐缓冲液（5 mM，pH 6.5）-0.3 M磷酸四丁铵溶液（500:500:15，v/v/v）组成。柱流出物通过荧光光谱法监测，激发波长设定为369 nm，发射波长为426 nm。研究了喜树碱及其开环形式在水溶液、血浆中以及甲醇提取后的化学稳定性。所提出的方法经过验证，并应用于大鼠的药代动力学研究。