Department of Chemistry, Faculty of Science and Arts, Hitit University, Corum, Turkey.
Talanta. 2010 Sep 15;82(4):1528-37. doi: 10.1016/j.talanta.2010.07.037. Epub 2010 Jul 23.
In this study, pK(a) values were determined using the dependence of the retention factor on the pH of the mobile phase for three ionizable substances, namely, enalapril, lercanidipine and ramipril (IS). The effect of the mobile phase composition on the ionization constant was studied by measuring the pK(a) at different methanol-water mixtures, ranging between 50 and 65% (v/v), using LC-DAD method. Two simple, accurate, precise and fully validated analytical methods for the simultaneous determination of enalapril and lercanidipine in combined dosage forms have been developed. Separation was performed on an X-Terra RP-18 column (250 mm x 4.60mm ID x 5 microm) at 40 degrees C with the mobile phase of methanol-water 55:45 (v/v) adjusted to pH 2.7 with 15 mM orthophosphoric acid. Isocratic elution was performed in less than 12 min with a flow rate of 1.2 mL min(-1). Good sensitivity for the analytes was observed with DAD detection. The LC method allowed quantitation over the 0.50-20.00 microg mL(-1) range for enalapril and lercanidipine. The second method depends on first derivative of the ratio-spectra by measurements of the amplitudes at 219.7 nm for enalapril and 233.0 nm for lercanidipine. Calibration graphs were established for 1-20 microg mL(-1) for enalapril and 1-16 microg mL(-1) lercanidipine, using first derivative of the ratio spectrophotometric method. Both methods have been extensively validated. These methods allow a number of cost and time saving benefits. The described methods can be readily utilized for analysis of pharmaceutical formulations. The methods have been applied, without any interference from excipients, for the simultaneous determination of these compounds in tablets. There was no significant difference between the performance of the proposed methods regarding the mean values and standard deviations.
在这项研究中，使用保留因子随流动相 pH 的变化来确定三种可电离物质（即依那普利、盐酸乐卡地平利和雷米普利（IS）的 pK(a) 值。通过测量在不同甲醇-水混合物中的 pK(a) 值，研究了流动相组成对离解常数的影响，甲醇-水混合物的比例范围为 50%至 65%（v/v），使用 LC-DAD 法。已经开发了两种简单、准确、精密且完全验证的分析方法，用于同时测定组合制剂中的依那普利和盐酸乐卡地平。分离在 X-Terra RP-18 柱（250mm×4.60mm ID×5μm）上进行，在 40°C 下，流动相为甲醇-水 55:45（v/v），用 15mM 正磷酸调至 pH2.7。在 1.2mL/min 的流速下，12min 内完成等度洗脱。用 DAD 检测对分析物具有良好的灵敏度。LC 法允许在 0.50-20.00μg/mL 范围内定量依那普利和盐酸乐卡地平。第二种方法依赖于比率光谱的一阶导数，通过测量依那普利在 219.7nm 和盐酸乐卡地平在 233.0nm 的振幅。对于依那普利和盐酸乐卡地平，建立了 1-20μg/mL 和 1-16μg/mL 的校准曲线，使用比率分光光度法的一阶导数。两种方法都经过了广泛的验证。这些方法可以节省大量的成本和时间。所描述的方法可用于分析药物制剂。这些方法可用于片剂中这些化合物的同时测定，无需赋形剂的干扰。所提出的方法在平均值和标准偏差方面没有显著差异。
