SENSITIVE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC METHOD FOR DIRECT SEPARATION OF LABETALOL STEREOISOMERS IN BIOLOGICAL-FLUIDS USING AN ALPHA-1-ACID GLYCOPROTEIN STATIONARY-PHASE

被引:11
作者
DOROUDIAN, A
YELESWARAM, K
RURAK, DW
ABBOTT, FS
AXELSON, JE
机构
[1] UNIV BRITISH COLUMBIA,FAC PHARMACEUT SCI,DIV PHARMACEUT & BIOPHARMACEUT,2146 E MALL,VANCOUVER V6T 1Z3,BC,CANADA
[2] UNIV BRITISH COLUMBIA,FAC MED,DEPT OBSTET & GYNECOL,VANCOUVER V6T 1Z3,BC,CANADA
[3] UNIV BRITISH COLUMBIA,DIV PHARMACEUT CHEM,VANCOUVER V6T 1Z3,BC,CANADA
来源
JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS | 1993年 / 619卷 / 01期
基金
英国医学研究理事会;
关键词
D O I
10.1016/0378-4347(93)80448-D
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
A chiral high-performance liquid chromatographic assay for the separation of the four stereoisomers of labetalol, an antihypertensive, in biological fluids has been developed. Baseline separation of the isomers was achieved using an alpha1-acid glycoprotein stationary phase. No interference from endogenous substances was observed following extraction from various biological fluids obtained from pregnant (ewe and fetus) and non-pregnant sheep. The concentration of the individual isomers of labetalol was determined by first measuring the total concentration of racemic labetalol obtained from an achiral assay followed by reassay of each sample by the chiral method after which, by using the estimate of the percentage of each individual isomer, the individual concentration of each of the four isomers was determined. The mobile phase was 0.02 M phosphate buffer containing 0.015 M tetrabutylammonium phosphate. The pH of the mobile phase was adjusted to 7.10. The detector was set at an excitation wavelength of 230 nm and emission wavelength of 400 nm to monitor the nascent fluorescence intensity of the isomers of labetalol. The limit of detection of the individual isomers was 0.15 ng (0.6 ng of injected racemic labetalol). The assay was linear over the range 0.6-15.0 ng of labetalol (injected) with the intra- and inter-day mean coefficients of variation being less than 9.0 and 6.0%, respectively. Application of the assay in the study of pharmacokinetics of the stereoisomers of labetalol in sheep following administration of racemic labetalol has been demonstrated.
引用
收藏
页码:79 / 86
页数:8
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