高效液相色谱法用于肾移植患者中环孢素A及其两种代谢物的治疗药物监测

High-performance liquid chromatographic method for therapeutic drug monitoring of cyclosporine A and its two metabolites in renal transplant patients.

作者信息

Brozmanová H, Grundmann M, Safarcík K, Jegorov A

机构信息

Institute of Clinical Pharmacology, University Hospital and Medico-Social Faculty, University of Ostrava, Czech Republic.

出版信息

J Chromatogr B Biomed Sci Appl. 2000 Nov 10;749(1):93-100. doi: 10.1016/s0378-4347(00)00384-4.

DOI:10.1016/s0378-4347(00)00384-4

PMID:11129082

Abstract

A novel fast HPLC method was developed for the determination of cyclosporine A (CyA) and its two metabolites M17 (AM1) and M21 (AM4N) in blood. Whole blood was precipitated with zinc sulphate, extracted with diethyl ether, evaporated, dissolved in aqueous methanol and partitioned twice with n-hexane. Chromatography was carried out using a microbore RP-column under isocratic elution with acetonitrile-methanol-water (200:80:140, v/v/v) at 70 degrees C and a detector set at 205 nm. Linearity for all three compounds was tested in the range of 1-1000 ng/ml. Recovery was 97-109%, and a coefficient of variation was 1.6-8.8% depending on the particular compound and its concentration. The method was used for a group of renal transplant patients having an inadequate response to CyA therapy in order to evaluate the possible role of CyA and its metabolites on the occurrence of hypertension and other toxicological events.

摘要

开发了一种新型快速高效液相色谱法，用于测定血液中环孢素A（CyA）及其两种代谢物M17（AM1）和M21（AM4N）。全血用硫酸锌沉淀，用乙醚萃取，蒸发，溶于甲醇水溶液，并用正己烷萃取两次。使用微径反相柱在70℃下以乙腈-甲醇-水（200:80:140，v/v/v）等度洗脱进行色谱分析，检测器设置在205nm。在1-1000ng/ml范围内测试了所有三种化合物的线性。回收率为97-109%，变异系数为1.6-8.8%，具体取决于特定化合物及其浓度。该方法用于一组对CyA治疗反应不足的肾移植患者，以评估CyA及其代谢物在高血压和其他毒理学事件发生中的可能作用。