Matsushima E, Sato T
Biological Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
J Chromatogr. 1992 Jan 17;573(2):339-44. doi: 10.1016/0378-4347(92)80141-c.
A column liquid chromatographic method using electrochemical detection has been developed for determination of an antiarrhythmic agent, bisaramil, and its metabolite in plasma. The plasma was fractionated by extraction with chloroform and chloroform-ethanol, and each fraction was dried and dissolved in ethyl acetate. After back-extraction into an acidic buffer, bisaramil was chromatographed on a reversed-phase column, and the metabolite, which has a higher polarity, was analysed by ion-pairing chromatography. Calibration curves were linear over the concentration range 2-200 ng/ml with coefficients of variation, within-day or day-to-day, not exceeding 5% at any level. The limits of detection of bisaramil and its metabolite were 0.5 and 1 ng/ml, respectively, using 0.5 ml of plasma. The dual-electrode detector was operated in the screening mode of oxidation (electrode 1, +0.55 V; electrode 2, +0.8 V), providing a greater specificity and reducing the background noise. This procedure was applied to a large number of samples in a pharmacokinetic study at the therapeutic dose.
已开发出一种采用电化学检测的柱液相色谱法，用于测定血浆中的抗心律失常药物比沙米及其代谢物。血浆通过用氯仿和氯仿 - 乙醇萃取进行分离，每个馏分经干燥后溶解于乙酸乙酯中。在反萃取到酸性缓冲液中后，比沙米在反相柱上进行色谱分析，而极性较高的代谢物则通过离子对色谱法进行分析。校准曲线在2 - 200 ng/ml的浓度范围内呈线性，日内或日间变异系数在任何水平下均不超过5%。使用0.5 ml血浆时，比沙米及其代谢物的检测限分别为0.5和1 ng/ml。双电极检测器在氧化筛选模式下运行（电极1，+0.55 V；电极2，+0.8 V），具有更高的特异性并降低了背景噪声。该方法应用于治疗剂量的药代动力学研究中的大量样品。
