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一种用于高效液相色谱法测定抗肿瘤二价和四价铂配合物的灵敏柱后衍生化/紫外检测系统。

A sensitive postcolumn derivatization/UV detection system for HPLC determination of antitumor divalent and quadrivalent platinum complexes.

作者信息

Kizu R, Yamamoto T, Yokoyama T, Tanaka M, Miyazaki M

机构信息

Faculty of Pharmaceutical Sciences, Kanazawa University 13-1, Japan.

出版信息

Chem Pharm Bull (Tokyo). 1995 Jan;43(1):108-14. doi: 10.1248/cpb.43.108.

Abstract

A sensitive postcolumn derivatization/UV detection system has been developed for HPLC analysis of antitumor divalent and quadrivalent platinum complexes. It is based on the derivatization of platinum complexes by reaction with sodium bisulfite to corresponding product(s) which has enhanced absorptivity at 280-300 nm. Platinum complexes examined in this study were cisplatin, carboplatin and oxaliplatin (divalent platinum complexes) and oxoplatin and tetraplatin (quadrivalent ones). The proposed detection system was sensitive to all these complexes. Under the detection conditions optimized for individual complexes, the HPLC gave linear relationships between the complex concentration and the peak height. Detection limits at 290 nm with 100 microliters injection were 20 nM for cisplatin, 40 nM for oxoplatin, 60 nM for carboplatin and tetraplatin and 100 nM for oxaliplatin (S/N = 3 at 0.005 AUFS). The proposed system was successfully applied for the determination of cisplatin and oxoplatin in plasma and urine. Pharmacokinetic behavior of oxoplatin and its reduced product cisplatin following a single intravenous injection of oxoplatin in rabbits has been discussed.

摘要

已开发出一种用于高效液相色谱(HPLC)分析抗肿瘤二价和四价铂配合物的灵敏柱后衍生化/紫外检测系统。该系统基于铂配合物与亚硫酸氢钠反应生成相应产物,这些产物在280 - 300 nm处具有增强的吸光度。本研究中检测的铂配合物有顺铂、卡铂和奥沙利铂(二价铂配合物)以及奥索铂和四铂(四价铂配合物)。所提出的检测系统对所有这些配合物都很灵敏。在针对各配合物优化的检测条件下,HPLC给出了配合物浓度与峰高之间的线性关系。进样100微升时,在290 nm处的检测限分别为:顺铂20 nM,奥索铂40 nM,卡铂和四铂60 nM,奥沙利铂100 nM(在0.005 AUFS时信噪比为3)。所提出的系统已成功应用于血浆和尿液中顺铂和奥索铂的测定。讨论了家兔单次静脉注射奥索铂后奥索铂及其还原产物顺铂的药代动力学行为。

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