Comparison between two methods for the determination of the total and free ( R)- and ( S)-disopyramide in plasma using an α 1-acid glycoprotein column

Abstract

Two different high-performance liquid chromatographic systems for the determination of the total and free ( R)- and ( S)-disopyramide (DP) in plasma and urine were compared. In method I a Nucleosil C 8 column was coupled in series with an α 1-acid glycoprotein column. Method II consisted of two systems; a LiChrosorb Si 60 column was used for the determination of the racemic drug concentration and the R/S ratio was determined on an α 1-acid glycoprotein column. The recovery of ( R)- and ( S)-DP from plasma was >97% in both methods. The precisions of the ( R)- and ( S)-DP determinations in plasma are high with both methods. The relative standard deviations for the determination of the free concentration do not exceed 6.5% at 1.59 μg/ml racemic DP. Method II is preferred as it can also be used to determine the concentration of ( R)- and ( S)-monodesisopropyldisopyramide. It is also easier to avoid disturbances from endogenous compounds in plasma samples with method II than with method I. It was observed that DP was incorporated into urine sediment during storage. A simple ultrasonic treatment of the urine samples was demonstrated to release DP from the sediment.