Osman Afaf Osman
National Organization for Drug Control and Research, 6 Abu Hazem St Pyramids, PO Box 29, Cairo, Egypt.
J AOAC Int. 2009 Sep-Oct;92(5):1373-81.
The objective of this study is to develop validated stability-indicating spectrofluorometric, TLC-densitometric, and HPLC methods for the determination of rabeprazole sodium and its degradation products. The first method was based on measuring the fluorescence intensity of the drug at 416 and 311 nm for the emission and at 320 and 274 nm for the excitation for acid and oxidized solutions, respectively. The second method was based on the separation of the drug from its acidic and oxidized degradation products followed by densitometric measurement of the intact drug spot at 284 nm. The separation was carried out on Fluka TLC sheets of silica gel 60 F254 using isopropyl alcohol--30% ammonia (80 + 2, v/v) mobile phase. The third method was based on HPLC separation of rabeprazole sodium from its acidic and oxidized degradation products on a reversed-phase Waters Nova-Pak C18 column using 0.05 M potassium dihydrogen phosphate-methanol-acetonitrile (5 + 3 + 2, v/v/v) pH 7 +/- 0.2 mobile phase. The proposed procedures were successfully applied for the determination of rabeprazole sodium in pure form, laboratory-prepared mixtures, tablet, and expired batch. The obtained results were statistically compared with those of a reported method and validated according to United States Pharmacopeia guidelines. Two main acidic degradation products of the drug were separated and subjected to IR spectrometry and MS to confirm their structures, and the schemes for their formation were elucidated.
本研究的目的是开发经过验证的稳定性指示荧光分光光度法、薄层色谱-密度测定法和高效液相色谱法，用于测定雷贝拉唑钠及其降解产物。第一种方法是分别测量药物在酸性和氧化溶液中的荧光强度，在发射波长416 nm和311 nm以及激发波长320 nm和274 nm处进行测量。第二种方法是将药物与其酸性和氧化降解产物分离，然后在284 nm处对完整药物斑点进行密度测定。分离在硅胶60 F254的弗洛卡薄层板上进行，使用异丙醇-30%氨水（80 + 2，v/v）作为流动相。第三种方法是在反相沃特世Nova-Pak C18柱上，使用0.05 M磷酸二氢钾-甲醇-乙腈（5 + 3 + 2，v/v/v）pH 7 ± 0.2的流动相，通过高效液相色谱法将雷贝拉唑钠与其酸性和氧化降解产物分离。所提出的方法成功应用于纯品、实验室制备的混合物、片剂和过期批次中雷贝拉唑钠的测定。将所得结果与报道方法的结果进行统计学比较，并根据美国药典指南进行验证。分离出该药物的两种主要酸性降解产物，并对其进行红外光谱和质谱分析以确认其结构，阐明了它们的形成机制。
