Verapamil and Norverapamil Determination in Human Plasma by Gas-Liquid Chromatography Using Nitrogen-Phosphorus Detection: Application to Single-Dose Pharmacokinetic Studies

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Abstract
A sensitive (to 0.5 ng/ml) and specific method for the determination of verapamil [a C channel blocker used in the treatment of cardiac arrhythmias] and norverapamil which utilizes gas-liquid chromatography with nitrogen-phosphorus detection is described. A basic extraction with acid back-wash and final basic reextraction is used for the preparation of plasma samples. Standard curves using .alpha.-isopropyl-.alpha.-[(N-methyl-N-homoveratryl)-.beta.-aminoethyl]-3,4-dimethoxyphenylacetonitrile hydrochloride (D-517) are linear for concentrations from 0.5-200 ng/ml for both verapamil and norverapamil. Within-day and between-day reproducibility is good with a coefficient of variation < 10% for all concentrations. Recovery is complete for both verapamil and norverapamil. Applicability of the method is demonstrated by a pharmacokinetic study in a normal volunteer who received 10 mg verapamil hydrochloride by i.v. infusion.