Department of Pharmaceutical Chemistry, Bharati Vidyapeeth University, Poona College of Pharmacy, Pune, Maharashtra 411038, India.
J Pharm Biomed Anal. 2009 Dec 5;50(5):787-93. doi: 10.1016/j.jpba.2009.06.026. Epub 2009 Jun 21.
In the present study, comprehensive stress testing of tenatoprazole was carried out according to ICH guideline Q1A (R2). Tenatoprazole was subjected to stress conditions of hydrolysis, oxidation, photolysis and neutral decomposition. Additionally, the solid drug was subjected to 50 degrees C for 60 days in dry-bath, and to the combined effect of temperature and humidity at 40 degrees C/75% RH. Extensive degradation was found to occur in acidic, neutral and oxidative conditions. Mild degradation was observed in basic conditions. The drug is relatively stable in the solid-state. The products formed under different stress conditions were investigated by LC and LC-MS. Successful separation of drug from degradation products formed under stress conditions was achieved on a Chemito ODS-3 column [C18 (5 microm, 250 mm x 4.6 mm, i.d.)] using methanol: 0.01 M acetate buffer pH 4.5 adjusted with glacial acetic acid (55:45) as the mobile phase at flow rate of 1 mL/min and the peak was detected using a UV detector set at 306 nm. The LC-MS m/z values and fragmentation patterns of degradation products formed under different stress conditions were studied and characterized through LC-MS fragmentation. Based on the results, degradation pathway for drug has been proposed.
在本研究中，根据 ICH 指南 Q1A（R2）对替那拉唑进行了全面的稳定性考察。替那拉唑经受了水解、氧化、光解和中性分解的应力条件。此外，将固体制剂在干热浴中于 50°C 下放置 60 天，并在 40°C/75%RH 的温度和湿度的联合作用下进行处理。在酸性、中性和氧化条件下发现广泛的降解。在碱性条件下观察到温和的降解。该药物在固态下相对稳定。通过 LC 和 LC-MS 研究了在不同应激条件下形成的产物。在 Chemito ODS-3 柱[C18（5 微米，250 毫米 x 4.6 毫米，内径）]上，使用甲醇：0.01 M 乙酸盐缓冲液 pH 4.5（用冰醋酸调节）作为流动相，以 1 mL/min 的流速成功地将药物从应激条件下形成的降解产物中分离出来，并用 UV 检测器在 306nm 处检测到峰。通过 LC-MS 碎片研究并表征了在不同应激条件下形成的降解产物的 LC-MS m/z 值和碎片模式。基于这些结果，提出了药物的降解途径。
