High performance liquid chromatography of procainamide and N-acetylprocainamide in human blood plasma

Procainamide is used in antiarrhythmic therapy, and the need to monitor the drug concentration as well as its major plasma metabolite, N-acetyl-procainamide, is well established. An assay designed for the routine clinical therapeutic drug monitoring laboratory has been developed. A 0.5-ml aliquot of blood plasma is treated with 0.1 ml of internal standard solution, and the mixture is alkalinized. The drug, its metabolite, and the internal standard, N-propionyl procainamide are extracted with methylene chloride. After evaporation to dryness and addition of 0.3 ml of mobile phase, a volume of 0.1 ml is injected onto a liquid chromatograph equipped with spectrofluorimetric detection, which has a better specificity than UV absorptiometric detection. The between-day coefficient of variation was 3.5% for procainamide and 5% for N-acetylprocainamide. The sensitivity of this technique permits detection of 0.1 micrograms/ml of procainamide and 0.25 micrograms/ml of N-acetylprocainamide. Several drugs that are often present in patients receiving procainamide were shown not to interfere.