Reverse-phase liquid chromatography and pharmacokinetic study of two hydroxylated analogues of quinidine in dogs.

Two hydroxylated analogues of quinidine with antiarrhythmic properties, 3S-hydroxyquinidine and 3R-hydroxydihydroquinidine were assayed by reverse-phase high-performance liquid chromatography. The analytical technique uses plasma protein precipitation and direct injection on a C18 column, with an isocratic mobile phase and spectrofluorometric detection. 3R-Hydroxyquinidine is employed as the internal standard. Linearity is verified up to 5 mg/L for the two drugs; concentrations between 0.5 and 2.5 mg/L were measured with a CV of 0.5-2.07% for a given day and a sensitivity limit of 50 micrograms/L. Plasma concentration-time profiles and pharmacokinetic parameters in three dogs are presented after intravenous or oral administration. A significant difference is observed in terminal half-life, terminal rate constant, and total clearance of the two polar analogues of quinidine.