National and Kapodistrian University of Athens, Faculty of Pharmacy, Laboratory of Pharmaceutical Analysis, Panepistimiopolis, Athens GR 157 71, Greece.
National and Kapodistrian University of Athens, Faculty of Pharmacy, Laboratory of Pharmaceutical Analysis, Panepistimiopolis, Athens GR 157 71, Greece.
Talanta. 2018 Jun 1;183:131-141. doi: 10.1016/j.talanta.2018.02.068. Epub 2018 Feb 17.
A hydrophilic interaction liquid chromatography method with diode array detection (HILIC-DAD) was developed and validated for the simultaneous determination of impurities in extended-release fixed-dose combination tablets containing rosuvastatin and metformin in a ratio 1:100. The analytes were separated by hydrophilic interaction liquid chromatography using an XBridge®-HILIC analytical column under isocratic elution. The mobile phase was composed of ammonium formate at 150 mM containing 0.05% diethylamine (pH 8.5)/acetonitrile, 4/96 (v/v) and pumped at a flow rate of 0.5 mL min. Method validation was performed according to ICH guidelines. The calibration curves for rosuvastatin, metformin and their seven impurities showed good linearity (r > 0.994) within the calibration ranges tested. The intra- and inter-day R.S.D. values were less than 4.5%, while the relative percentage error Er was less than 2.7% for all compounds. Accelerated stability studies performed under various stress conditions including hydrolysis, oxidation and heat proved the selectivity of the procedure. A run time of less than 25 min for each sample made it possible to analyze a large number of samples per day. The method is the first reported application of HILIC for the analysis of impurities in fixed-dose combination tablets containing rosuvastatin and metformin and it can be used for the quality control of these drugs.
建立并验证了一种亲水作用色谱-二极管阵列检测法（HILIC-DAD），用于同时测定以 1:100 比例（罗舒伐他汀：二甲双胍）制成的固定剂量复方制剂中罗舒伐他汀和二甲双胍的杂质。使用 XBridge®-HILIC 分析柱在等度洗脱条件下，通过亲水作用色谱法分离分析物。流动相由 150mM 甲酸铵（含 0.05%二乙胺，pH8.5）/乙腈，4/96（v/v）组成，流速为 0.5mL/min。方法验证符合 ICH 指南。在测试的校准范围内，罗舒伐他汀、二甲双胍及其七种杂质的校准曲线均具有良好的线性（r>0.994）。所有化合物的日内和日间 R.S.D.值均小于 4.5%，相对百分比误差 Er 均小于 2.7%。在包括水解、氧化和热在内的各种条件下进行的加速稳定性研究证明了该方法的选择性。每个样品的运行时间不到 25 分钟，可实现每天分析大量样品。该方法是首次报道用于分析含有罗舒伐他汀和二甲双胍的固定剂量复方制剂中杂质的 HILIC 应用，可用于这些药物的质量控制。
