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在十亿分之一浓度范围内,采用毛细管电泳法对氧氟沙星对映体进行定量,用于体外药物吸收研究。

Quantitation of the enantiomers of ofloxacin by capillary electrophoresis in the parts per billion concentration range for in vitro drug absorption studies.

作者信息

Awadallah Bilal, Schmidt Peter C, Wahl Martin A

机构信息

Department of Pharmaceutical Technology, Eberhard-Karls-University Tübingen, Auf der Morgenstelle 8, D-72076 Tübingen, Germany.

出版信息

J Chromatogr A. 2003 Feb 21;988(1):135-43. doi: 10.1016/s0021-9673(02)02015-0.

DOI:10.1016/s0021-9673(02)02015-0
PMID:12647828
Abstract

Ofloxacin, a chiral fluoroquinolone, possesses two optical isomers. The antibacterial activity of S-(-)-ofloxacin is reported to be 8-128 times higher than that of R-(+)-ofloxacin. A capillary zone electrophoresis method has been developed to quantify the enantiomers of ofloxacin in high diluted samples (20-700 ng/ml for each enantiomer). After fluid-fluid extraction of ofloxacin from physiological solution electrokinetic injection was employed to improve the sensitivity. The method was optimised using a central composite design. Four experimental factors were investigated: the background electrolyte concentration, the methyl-beta-cyclodextrin concentration, the buffer pH and the temperature. The amount migrated into the capillary, determined by the peak area, the resolution between the ofloxacin enantiomers, the migration time and the generated current were evaluated as responses. The quantification limit is 11.4 ng/ml for S-ofloxacin and 10.8 ng/ml for R-ofloxacin. The method has shown good validation data in terms of precision and recovery rate.

摘要

氧氟沙星是一种手性氟喹诺酮类药物,有两种光学异构体。据报道,S-(-)-氧氟沙星的抗菌活性比R-(+)-氧氟沙星高8至128倍。已开发出一种毛细管区带电泳方法,用于定量高稀释样品(每种对映体浓度为20至700 ng/ml)中氧氟沙星的对映体。从生理溶液中进行液-液萃取后,采用电动进样提高灵敏度。该方法采用中心复合设计进行优化。研究了四个实验因素:背景电解质浓度、甲基-β-环糊精浓度、缓冲液pH值和温度。将通过峰面积测定的进入毛细管的量、氧氟沙星对映体之间的分离度、迁移时间和产生的电流作为响应进行评估。S-氧氟沙星的定量限为11.4 ng/ml,R-氧氟沙星的定量限为10.8 ng/ml。该方法在精密度和回收率方面显示出良好的验证数据。

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