Abstract
A method for quantitation of (+) -(R) -verapamil and (-)-(S)-verapamil concentrations in serum was developed for the purpose of determining verapamil enantiomer pharmacokinetics after racemate administration. Two high-performance liquid chromatographic (HPLC) systems were used. A reversed-phase HPLC system was first used to quantitate summed concentrations of the enantiomers ((R+S)-verapamil) using fluorescence detection. Mobile phase eluate containing the (R+S)-verapamil was collected from the detector outlet, and the individual enantiomers in the residue were separated using a chiral column with a stationary phase of silica-bound α1-acid glycoprotein. Peak heights were measured and peak height ratios of R/S were determined. The measured (R+S)-verapamil concentration from the achiral system was used with the R/S ratio from the chiral system to determine the serum concentrations of the individual enantiomers. The pharmacokinetics of (+)-(R)-verapamil and (-)-(S)-verapamil were studied in a healthy volunteer who received a single oral dose (120 mg) and a 30 minute intravenous infusion (15 mg) of racemic verapamil hydrochloride. The pharmacokinetic parameters obtained for the individual enantiomers (half-life, steady-state volume of distribution, body clearance, bioavailability) agreed well with reported values from studies in which enantiomers were administered on separate occasions or in which one enantiomer was dideuterated.