Determination of an ultrashort-acting antihypertensive dihydropyridine, clevidipine, in blood using capillary gas chromatography–mass spectrometry and of the primary metabolite using liquid chromatography and fluorescence detection

Abstract

A method for the quantitative determination of a new ultrashort-acting dihydropyridine, clevidipine (butyroxymethyl methyl 4-(2′,3′-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate), in whole blood with capillary gas chromatography–mass spectrometry with negative ion chemical ionisation is presented. The rapidly metabolised drug is stabilised in blood using sodium dodecyl sulphate (SDS) which prevents ester hydrolysis. The analytical procedure involves liquid–liquid extraction prior to gas chromatographic determination with a limit of quantification of 0.5 nmol/l blood. The acidic primary metabolite (methyl 4-(2′,3′-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate), MI, can be determined with liquid chromatography and fluorescence detection using a similar sample work-up procedure. Ascorbic acid is then added before sampling to prevent oxidation. The limit of quantification for MI is 50 nmol/l blood.