Stereoselective determination of fenfluramine enantiomers in rat liver microsomal incubates.
An enantioselective assay for l- and d-fenfluramine in rat liver microsomal incubates was developed. The method involves extraction of fenfluramine from the microsomal incubates, and formation of fenfluramine diastereomeric derivatives with the chiral reagent S-(-)-N-trifluoroacetyl prolyl chloride. Separation and quantitation of the diastereomeric fenfluramine derivatives are carried out by a capillary gas chromatographic system with flame ionization detection. The assay is linear from 1 to 50 microg/ml for each enantiomer. The analytical method affords average recoveries of 92.28 and 96.44% for l- and d-fenfluramine, respectively. The limits of detection and quantitation for the method are 0.1 and 1.0 microg/ml for the l- and d-fenfluramine isomers, respectively. The reproducibility of the assay was <10% (RSD). The method allowed study of the depletion of l- and d-fenfluramine in rat liver microsomal incubates. The stereoselectivity of fenfluramine phase I metabolism was observed.
Zeng
S
S
School of Pharmacy, Zhejiang University, Hangzhou, People's Republic of China. 25@ml.zjmu.edu.cn
Mao
H Q
HQ
D000818:Animals; D002138:Calibration; D002849:Chromatography, Gas / Q000379:methods; D005277:Fenfluramine / Q000032:analysis* / Q000737:chemistry; D008862:Microsomes, Liver / Q000737:chemistry*; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
D005277:Fenfluramine