Longer plasma half-life for procainamide utilizing a very sensitive high performance liquid chromatography assay.

The reported biological half-life of the antiarrhythmic drug procainamide (PA) is between 2 and 4 h. To reassess this, the disposition kinetics of the drug and its pharmacologically active metabolite, N-acetyl procainamide (NAPA), were determined using a newly developed high performance liquid chromatography (HPLC) method. The assay involved extraction from plasma of PA and NAPA with methylene chloride, followed by a brief washing of the extract with water, separation and evaporation of the organic layer, reconstitution in the mobile phase [water/methanol/acetic acid/triethylamine (74:25:1:0.03)], and injection into the HPLC system. At an ultraviolet light detection wavelength of 280 nm, the samples were chromatographed on a reverse-phase column. The minimum quantifiable concentration was 0.005 microgram/ml for both the drug and its metabolite. With this sensitivity it was possible to measure PA and NAPA plasma concentrations in samples taken as late as 24 h after single 375-mg oral doses of PA HCl to 13 healthy volunteers. When only the data points up to 12 h were included in the calculation, the drug t1/2 was 3.50 +/- 0.82 h (mean +/- SD) and in agreement with those reported previously. However, the t1/2 became significantly longer (8.52 +/- 3.58 h) when the 16- and 24-h data points were also included. The t1/2 of NAPA was 8.06 +/- 1.33 h and close to the reported values.