Liquid chromatographic separation and measurement of optical isomers of aminoglutethimide and its acetyl metabolite in plasma, saliva, and urine.

Abstract:

:An accurate and specific liquid chromatographic method for the separation and analysis of the R(+) and S(-) enantiomers of both aminoglutethimide (AG) and its acetylated metabolite (AcAG) in plasma, saliva, and urine is described. The separation was achieved by use of two serial Chiralcel OD columns [cellulose tris(3,5-dimethylphenyl carbamate)] with a mixture of hexane/isopropanol/methanol (65:17.5:17.5, per volume) as a mobile phase. The flow rate was 0.7 ml/min, and the compounds were detected in the effluent spectrophotometrically at 245 nm. The plasma, saliva, or urine sample (300 microliters) was extracted with dichloromethane after the addition of an equal volume of acetate buffer (pH 5.6) to the sample. The extraction recovery of the R(+) and S(-) enantiomers of AG and AcAG from plasma, saliva, and urine at different concentrations under these conditions was > 80.9%. No interference from any endogenous substance or concomitantly used drug was observed. The ratio of the peak area of R(+) and S(-) enantiomers of both AG and AcAG/internal standard was linearly (r > or = 0.995) related to concentration in the range 0.83-40.0 micrograms/ml, and the coefficient of variation (CV) at different concentrations was consistently < or = 13%. We are presently employing this method to study the pharmacokinetics of each of these enantiomers in breast cancer patients.

journal_name

Ther Drug Monit

authors

Alshowaier IA,el-Yazigi A,Ezzat A,el-Warith AA,Nicholls PJ

doi

10.1097/00007691-199510000-00017

subject

Has Abstract

pub_date

1995-10-01 00:00:00

pages

538-43

issue

5

eissn

0163-4356

issn

1536-3694

journal_volume

17

pub_type

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