Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research-Ahmedabad(NIPER-A), (Ministry of Chemicals and Fertilizers, Government of India), Gandhinagar, Gujarat, India.
Eur J Mass Spectrom (Chichester). 2024 Jun;30(3-4):171-186. doi: 10.1177/14690667241262935. Epub 2024 Jul 26.
Exenatide is a synthetic glucagon-like peptide 1 analog, widely used in the management of type 2 diabetes mellitus. The stability of pharmaceutical products is significantly impacted by various environmental stress conditions. The present study reports the development of a validated reverse-phase high-performance liquid chromatography (RP-HPLC) stability-indicating method for the identification of force degradation products (DPs) of synthetic glucagon-like peptide-1 analog Exenatide using UHPLC-Orbitrap fusion mass spectrometer. Force degradation studies were performed by subjecting Exenatide to various stress conditions, such as hydrolytic, oxidative, photolytic and thermal to investigate the stability indicating ability of the method. Significant degradation was observed during acidic, oxidative, photolytic and thermal stress conditions. Exenatide and its major DPs identification and characterization were demonstrated by employing LC-HRMS and MS/MS method. In total, five major stress DPs were characterized, and their fragmentation pathway was proposed using MS/MS studies. Finally, the proposed RP-HPLC method was validated as per ICH guidance.
艾塞那肽是一种合成的胰高血糖素样肽 1 类似物，广泛用于 2 型糖尿病的治疗。药物产品的稳定性受到各种环境应激条件的显著影响。本研究报道了一种经验证的反相高效液相色谱（RP-HPLC）稳定性指示方法的开发，该方法使用 UHPLC-Orbitrap 融合质谱仪鉴定合成胰高血糖素样肽-1 类似物 Exenatide 的强制降解产物（DPs）。通过将 Exenatide 置于各种应激条件下（如水解、氧化、光解和热解）进行强制降解研究，以考察该方法的稳定性指示能力。在酸性、氧化、光解和热应激条件下观察到明显的降解。采用 LC-HRMS 和 MS/MS 方法对艾塞那肽及其主要 DPs 的鉴定和表征进行了验证。共鉴定了 5 个主要的应激 DPs，并通过 MS/MS 研究提出了它们的断裂途径。最后，根据 ICH 指南对所提出的 RP-HPLC 方法进行了验证。
