pH,缓冲量,度和温度对使用LC-HRMS降解塞马格卢提德溶液状态降解的作用:用于类药物输送的预制剂协议
Adarsh Malgave1, Sideequl Akbar1, Anumol Joseph1
1Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hajipur, Export Promotion Industrial Park (EPIP), Zandaha Road, NH322, Hajipur, Bihar 844102, India.
概括
塞马格卢提德 (SGL) 的稳定性受到pH值和温度的影响,在各种压力条件下确定了特定的杂质. 了解这些因素对于优化SGL配方和确保产品保质期至关重要.
科学领域:
- 制药化学 制药化学 制药化学
- 分析化学 分析化学
- 生物化学 生物化学
背景情况:
- 长期起作用的GLP-1受体激动剂塞马格卢提德 (SGL) 是一种易于降解的改性.
- 的降解可能会导致污染物影响药物的安全性,疗效和免疫性.
- 确保SGL的稳定性对于其制药开发和临床使用至关重要.
研究的目的:
- 为了研究pH值,温度,缓冲物种和度对SGL稳定性的影响.
- 用先进的分析技术识别和描述SGL的降解杂质.
- 为优化SGL配方,制造工艺和储存条件提供数据.
主要方法:
- 在各种热条件 (25°C至80°C) 和pH水平下进行了应力稳定性研究.
- 逆相超高性能液态色谱 (RP-UPLC) 用于杂质分离.
- 液体染色学高分辨率质谱法 (LC-HRMS) 用于杂质识别和分子量确定.
主要成果:
- 在SGL降解过程中确定了13种已知的杂质及其碎片.
- 在测试条件下,六种特定杂质 (例如,杂质4,m/z=2717.21) 始终在测试条件下形成.
- pH被确定为影响SGL热降解的关键因素,在特定的pH值中缺少某些杂质.
结论:
- 该研究阐明了基于质谱数据的赛马格卢 (SGL) 降解途径.
- 溶液状态稳定性数据对于优化制药过程和配方,包括PLGA配方,非常有价值.
- 这些发现将有助于确定SGL的适当储存条件,保质期和体内稳定性.
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