Katholieke Universiteit Leuven, Faculteit Farmaceutische Wetenschappen, Laboratorium voor Farmaceutische Analyse, O&N2, Herestraat 49, PB 923, B-3000 Leuven, Belgium.
J Pharm Biomed Anal. 2012 Mar 5;61:271-6. doi: 10.1016/j.jpba.2011.12.019. Epub 2011 Dec 23.
A reversed phase liquid chromatographic method with UV detection for the simultaneous determination of clopidogrel and acetylsalicylic acid and their related substances in combined oral formulations was developed and validated. Good separation was achieved on a Luna C18 column (150 mm × 4.6 mm, 3 μm) using gradient elution at a flow rate of 1 mL/min and a column temperature of 35 °C. UV detection was performed at 220 nm. The validation was performed according to the ICH guidelines. The method proved to be specific, sensitive (LOQ=0.975 μg/mL and 0.0384 μg/mL for clopidogrel and acetylsalicylic acid, respectively), linear in the concentration range from LOQ to 325 μg/mL for clopidogrel and from LOQ to 650 μg/mL for acetylsalicylic acid, precise (RSD values for intermediate precision <1%) and accurate with mean recovery values of 100.7% and 100.2% for clopidogrel and acetylsalicylic acid, respectively. Moreover, the solution stability and method robustness were examined. The method gives satisfactory separation of impurities of clopidogrel and acetylsalicylic acid and so it is suitable for quantification of the related substances as well as for the assay of the actives.
建立并验证了一种反相高效液相色谱法，用于同时测定复方口服制剂中氯吡格雷和阿司匹林及其有关物质。在 Luna C18 柱（150mm×4.6mm，3μm）上，以 1mL/min 的流速和 35℃的柱温进行梯度洗脱，实现了良好的分离。采用 UV 检测，检测波长为 220nm。验证符合 ICH 指南的要求。该方法具有专属性、灵敏度（氯吡格雷和阿司匹林的 LOQ 分别为 0.975μg/mL 和 0.0384μg/mL）、线性范围从 LOQ 至 325μg/mL（氯吡格雷）和 LOQ 至 650μg/mL（阿司匹林），精密度（中间精密度的 RSD 值<1%）和准确度良好，氯吡格雷和阿司匹林的平均回收率分别为 100.7%和 100.2%。此外，还考察了溶液稳定性和方法耐用性。该方法可对氯吡格雷和阿司匹林的杂质进行有效分离，因此适用于有关物质的定量测定以及活性成分的含量测定。
