Abdelrahman Maha M, Naguib Ibrahim A, El Ghobashy Mohamed R, Ali Nesma A
Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Alshaheed Shehata Ahmad Hegazy St., 62514 Beni-Suef, Egypt.
Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., 11562 Cairo, Egypt.
J Chromatogr Sci. 2018 Apr 1;56(4):317-326. doi: 10.1093/chromsci/bmx114.
Two accurate, sensitive and highly selective stability-indicating methods are developed and validated for simultaneous determination of Agomelatine (AGM) and its forced degradation products (Deg I and II). The first method is High-Performance Liquid Chromatography for separation and quantitation of AGM, Deg I and II on a C18 column (250 mm × 4.6 mm, 5 μm p.s) in isocratic mode by using a binary mixture of Potassium dihydrogen phosphate (0.05 M, pH adjusted to 2.9 with orthophosphoric acid): acetonitrile (60:40, v/v) at a flow rate of 2 mL/min. The components were detected at 230 nm over a concentration range of 0.5-10 μg/mL for AGM and 0.5-5 μg/mL for both Deg I and II. The second method is High-Performance Thin-Layer Chromatography, where AGM, Deg I and II were separated on silica gel HPTLC F254 plates using chloroform:methanol:ammonia solution (9:1:0.1, by volume) as a developing system. The separated bands were scanned at 230 nm over the concentration range of 0.2-1.2 μg/band for AGM in pure form and human plasma and 0.1-1 μg/band for both Deg I and II. The proposed methods were successfully applied for analysis of AGM in pharmaceutical formulations. The results obtained by the proposed methods were statistically compared to the reported HPLC method revealing high accuracy and good precision.
开发并验证了两种准确、灵敏且高选择性的稳定性指示方法，用于同时测定阿戈美拉汀（AGM）及其强制降解产物（降解产物I和II）。第一种方法是高效液相色谱法，在C18柱（250 mm×4.6 mm，5μm粒径）上，采用磷酸二氢钾（0.05 M，用正磷酸调节pH至2.9）：乙腈（60:40，v/v）的二元混合溶液，以等度模式、2 mL/min的流速分离并定量AGM、降解产物I和II。在230 nm波长下检测各组分，AGM的浓度范围为0.5 - 10μg/mL，降解产物I和II的浓度范围均为0.5 - 5μg/mL。第二种方法是高效薄层色谱法，在硅胶HPTLC F254板上，以氯仿：甲醇：氨溶液（9:1:0.1，体积比）作为展开系统分离AGM、降解产物I和II。在230 nm波长下扫描分离后的色带，纯品AGM及人血浆中AGM的浓度范围为0.2 - 1.2μg/条带，降解产物I和II的浓度范围均为0.1 - 1μg/条带。所提出的方法成功应用于药物制剂中AGM的分析。将所提出方法得到的结果与报道的高效液相色谱法进行统计学比较，结果显示该方法具有高准确性和良好精密度。
