Azougagh M, Elkarbane M, Bakhous K, Issmaili S, Skalli A, Iben Moussad S, Benaji B
Institut supérieur des professions infirmières et techniques de santé, Rabat, Morocco.
Institut supérieur des professions infirmières et techniques de santé, Rabat, Morocco.
Ann Pharm Fr. 2016 Sep;74(5):358-69. doi: 10.1016/j.pharma.2016.07.001. Epub 2016 Jul 27.
An innovative simple, fast, precise and accurate ultra-high performance liquid chromatography (UPLC) method was developed for the determination of diclofenac (Dic) along with its impurities including the new dimer impurity in various pharmaceutical dosage forms. An Acquity HSS T3 (C18, 100×2.1mm, 1.8μm) column in gradient mode was used with mobile phase comprising of phosphoric acid, which has a pH value of 2.3 and methanol. The flow rate and the injection volume were set at 0.35ml·min(-1) and 1μl, respectively, and the UV detection was carried out at 254nm by using photodiode array detector. Dic was subjected to stress conditions from acid, base, hydrolytic, thermal, oxidative and photolytic degradation. The new developed method was successfully validated in accordance to the International Conference on Harmonization (ICH) guidelines with respect to specificity, limit of detection, limit of quantitation, precision, linearity, accuracy and robustness. The degradation products were well resolved from main peak and its seven impurities, proving the specificity power of the method. The method showed good linearity with consistent recoveries for Dic content and its impurities. The relative percentage of standard deviation obtained for the repeatability and intermediate precision experiments was less than 3% and LOQ was less than 0.5μg·ml(-1) for all compounds. The new proposed method was found to be accurate, precise, specific, linear and robust. In addition, the method was successfully applied for the assay determination of Dic and its impurities in the several pharmaceutical dosage forms.
开发了一种创新的、简单、快速、精确且准确的超高效液相色谱（UPLC）方法，用于测定双氯芬酸（Dic）及其杂质，包括各种药物剂型中的新二聚体杂质。采用梯度模式的Acquity HSS T3（C18，100×2.1mm，1.8μm）色谱柱，流动相由pH值为2.3的磷酸和甲醇组成。流速和进样体积分别设定为0.35ml·min(-1)和1μl，使用光电二极管阵列检测器在254nm处进行紫外检测。Dic分别经受了酸、碱、水解、热、氧化和光解降解等强制降解条件。新开发的方法按照国际协调会议（ICH）指南在特异性、检测限、定量限、精密度、线性、准确度和稳健性方面成功进行了验证。降解产物与主峰及其七种杂质得到了很好的分离，证明了该方法的特异性。该方法对Dic含量及其杂质显示出良好的线性和一致的回收率。重复性和中间精密度实验获得的相对标准偏差百分比小于3%，所有化合物的定量限均小于0.5μg·ml(-1)。新提出的方法被发现准确、精密、特异、线性且稳健。此外，该方法成功应用于几种药物剂型中Dic及其杂质的含量测定。
