Assay of isradipine and of its major metabolites in biological fluids by capillary gas chromatography and chemical ionization mass spectrometry.
A method is described for the determination of isradipine, a dihydropyridine calcium antagonist, and five of its metabolites in plasma and urine. The neutral compounds were extracted in toluene and analysed in a wide-bore silica capillary column. The acidic compounds were extracted in two steps, then esterified with diazomethane and assayed separately using the same column. Detection was performed by negative-ion mass spectrometry with chemical ionization. The limit of detection of isradipine was 0.04 ng/ml when the compound was determined alone and 0.7 ng/ml when its oxidized metabolite was determined simultaneously. The limits of detection of the metabolites in plasma ranged from 0.15 to 2 ng/ml. The method was successfully used in conventional pharmacokinetic studies and in a multicentre study of population pharmacokinetics.
Jean
C
C
Biopharmaceutical Department, Sandoz Ltd., Basle, Switzerland.
Laplanche
R
R
D002121:Calcium Channel Blockers / Q000032:analysis* / Q000097:blood / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D017275:Isradipine; D011725:Pyridines / Q000032:analysis* / Q000097:blood / Q000652:urine; D011786:Quality Control; D012997:Solvents
D002121:Calcium Channel Blockers; D011725:Pyridines; D012997:Solvents; D017275:Isradipine