Enantioselective determination of felodipine and other chiral dihydropyridine calcium entry blockers in human plasma.
A sensitive method for the enantioselective determination of felodipine in human plasma is described. Following alkaline extraction with dichloromethane-pentane, racemic felodipine and its primary pyridine metabolite are simultaneously assayed using capillary gas chromatography on a DB-1 column, with electron-capture detection. The enantiomers of felodipine are quantitatively separated by high-performance liquid chromatography on a Chiralcel OJ column, containing tris(4-methylbenzoate)-modified cellulose coated on silica, and off-line detection using the same gas chromatographic system is applied. The limits of determination in plasma (and the inter-assay coefficient of variation (C.V.) at levels below 1 ng/ml) were 0.1 ng/ml (C.V. 13%) for felodipine, 0.1 ng/ml (C.V. 15%) for the enantiomers of felodipine and 0.3 ng/ml (C.V. 7%) for its pyridine metabolite. The method has proved to be applicable to several other chiral dihydropyridine calcium entry blockers, including nitrendipine, with comparable sensitivities.
Soons
P A
PA
Division of Pharmacology, University of Leiden, The Netherlands.
Roosemalen
M C
MC
Breimer
D D
DD
D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D004095:Dihydropyridines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D015736:Felodipine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D009568:Nitrendipine / Q000097:blood; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009568:Nitrendipine; D015736:Felodipine