Identification, isolation and structural characterization of forced degradation products of sotorasib using advanced analytical techniques

IF 2.5 Q2 CHEMISTRY, MULTIDISCIPLINARY Results in Chemistry Pub Date : 2024-09-18 DOI:10.1016/j.rechem.2024.101799

Shweta Mishra , Ashlesha Chauhan , R. Ramajayam

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Abstract

Sotorasib is a small molecule inhibitor and approved by USFDA for the treatment of non-small cell lung cancer (NSCLC). In the present study, forced degradation behavior of sotorasib was carried out by utilizing LC-MS/MS technique. As per ICH guidelines, the forced degradation is conducted in various conditions such as acidic, basic, oxidative, thermal and photolytic. A significant degradation was found in acidic, basic and oxidative conditions conversely sotorasib was found relatively stable in thermal and photolytic conditions. In acidic condition, two degradation products such as DP1 and DP3 were isolated. Also, DP3 is the common degradant obtained in both acidic and basic conditions. DP2 is obtained from oxidative conditions. All the isolated degradation products are new and not reported in the literature. All the degradation products are completely characterized by IR, ¹H NMR and mass spectroscopy. In conclusion, the scope of study will certainly useful in the regulatory requirements such as physiochemical stability of sotorasib, pharmacokinetic studies and clinical research related.

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利用先进分析技术识别、分离索托拉西布的强制降解产物并确定其结构特征

索托拉西布是一种小分子抑制剂，已被美国食品及药物管理局批准用于治疗非小细胞肺癌（NSCLC）。本研究利用 LC-MS/MS 技术对索托拉西布进行了强制降解。根据 ICH 指南，强制降解在酸性、碱性、氧化、热和光解等不同条件下进行。在酸性、碱性和氧化条件下，索托拉西布出现了明显的降解，相反，在热和光解条件下，索托拉西布则相对稳定。在酸性条件下，分离出两种降解产物，如 DP1 和 DP3。此外，DP3 是在酸性和碱性条件下都能得到的常见降解产物。DP2 是在氧化条件下得到的。所有分离出的降解产物都是新的，在文献中没有报道过。所有降解产物都通过红外光谱、1H NMR 和质谱进行了表征。总之，该研究范围将有助于满足索托拉西布的理化稳定性、药代动力学研究和临床研究等监管要求。

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