Jamali F, Alballa R S, Mehvar R, Lemko C H
Faculty of Pharmacy, University of Alberta, Edmonton, Canada.
Ther Drug Monit. 1988;10(1):91-6.
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.
据报道，抗心律失常药物普鲁卡因胺（PA）的生物学半衰期在2至4小时之间。为了重新评估这一点，使用新开发的高效液相色谱（HPLC）方法测定了该药物及其药理活性代谢物N - 乙酰普鲁卡因胺（NAPA）的处置动力学。该测定方法包括用二氯甲烷从血浆中提取PA和NAPA，然后用水对提取物进行短暂洗涤，分离并蒸发有机层，在流动相[水/甲醇/乙酸/三乙胺（74:25:1:0.03）]中复溶，并注入HPLC系统。在280nm的紫外光检测波长下，样品在反相柱上进行色谱分析。药物及其代谢物的最低可定量浓度均为0.005微克/毫升。基于这种灵敏度，有可能测量13名健康志愿者单次口服375毫克PA HCl后长达24小时采集的样本中的PA和NAPA血浆浓度。当仅将12小时以内的数据点纳入计算时，药物的t1/2为3.50±0.82小时（平均值±标准差），与先前报道的结果一致。然而，当也纳入16小时和24小时的数据点时，t1/2显著延长（8.52±3.58小时）。NAPA的t1/2为8.06±1.33小时，接近报道值。
