采用整体硅胶高效液相色谱柱快速灵敏地同时测定复方制剂中依折麦布和辛伐他汀的含量。

Rapid and sensitive simultaneous determination of ezetimibe and simvastatin from their combination drug products by monolithic silica high-performance liquid chromatographic column.

作者信息

Hefnawy Mohamed, Al-Omar Mohammed, Julkhuf Saeed

机构信息

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.

出版信息

J Pharm Biomed Anal. 2009 Oct 15;50(3):527-34. doi: 10.1016/j.jpba.2009.05.002. Epub 2009 May 13.

DOI:10.1016/j.jpba.2009.05.002

PMID:19487095

Abstract

A simple, precise and rapid high-performance liquid chromatography (HPLC) method has been developed and validated for the simultaneous determination of ezetimibe (EZE) and simvastatin (SIM) from their combination drug products. The applicability of monolithic LC phases in the field of quantitative analysis has been evaluated. The existing method with UV detection set at 240 nm was successfully transferred from a conventional silica column to a 10 cm x 4.6 mm i.d. monolithic silica column. By simply increasing the mobile phase flow rate, run time was about five-fold reduced and the consumption of mobile phase was about two-fold decreased, while the chromatographic resolution of the analytes remain unaffected. Ranitidine (RAN) was used as internal standard to guarantee a high level of quantitative performance. The method used a mobile phase consisted of acetonitrile-ammonium acetate (50 mM pH 5.0) (65:35, v/v). It was validated with respect to system suitability, specificity, limit of quantitation (LOQ) and detection (LOD), linearity, precision, accuracy, and recovery, respectively. The described method was linear over the range of 40-1200 ng ml(-1) (r=0.999) for both drugs. The LOD for EZE and SIM were 13.2+/-0.4029 and 13.3+/-0.4772 ng ml(-1), respectively. The LOQ were found to be 39.9+/-1.221 and 39.5+/-1.446 ng ml(-1) for EZE and SIM, respectively. The method is fast (less than 2.0 min) and is suitable for high-throughput analysis of the drug and ones can analyze 700 samples per working day, facilitating the processing of large-number batch samples.

摘要

已开发并验证了一种简单、精确且快速的高效液相色谱（HPLC）方法，用于同时测定复方制剂中的依折麦布（EZE）和辛伐他汀（SIM）。评估了整体式液相色谱柱在定量分析领域的适用性。现有的在240 nm处进行紫外检测的方法已成功从传统硅胶柱转移至内径为4.6 mm、长度为10 cm的整体式硅胶柱上。通过简单提高流动相流速，运行时间缩短了约五倍，流动相消耗量减少了约两倍，而分析物的色谱分离度不受影响。雷尼替丁（RAN）用作内标以确保高水平的定量性能。该方法使用由乙腈 - 醋酸铵（50 mM，pH 5.0）（65:35，v/v）组成的流动相。分别针对系统适用性、特异性、定量限（LOQ）和检测限（LOD）、线性、精密度、准确度和回收率进行了验证。所描述的方法对两种药物在40 - 1200 ng ml⁻¹范围内均呈线性（r = 0.999）。EZE和SIM的LOD分别为13.2 ± 0.4029和13.3 ± 0.4772 ng ml⁻¹。EZE和SIM的LOQ分别为39.9 ± 1.221和39.5 ± 1.446 ng ml⁻¹。该方法快速（少于2.0分钟），适用于药物的高通量分析，每个工作日可分析700个样品，便于处理大量批量样品。