Vol. 7, Issue 2, Part I (2025)

Targeted kinase inhibitors for treating MET (mesenchymal-epithelial transition factor), RET REarranged during Transfection), and MET-induced non-small cell lung cancer (NSCLC) include drugs like tepotinib, selpercatinib and capmatinib. To ensure the quality and safety of these drugs, stability studies are to be conducted. This review includes recent forced degradation studies using complementary in silico and experimental studies. The MET inhibitor tepotinib, which is used for NSCLC, produced five DPs between the values of m/z 511-527 under acidic, basic, oxidative, and photolytic stress conditions using UHPLC-QTOF-MS/MS. Zeneth an in-silico software, predicted eight possible degradation products (DPs) of tepotinib under the simulated stress conditions, but only five degradation products were actually formed in lab experiments i.e DP-1, 2, 3, 4, 5. Derek & Sarah which are the toxicity prediction tools, scanned the predicted degradation products DP-3, DP-5 as nephrotoxic and DP-3 as mutagenic respectively. RET kinase inhibitor selpercatinib, which is used for NSCLC and thyroid cancer, under acidic forced degradation conditions (stress testing), formed a single impurity called sel-1 (C₂₈H₂₉N₇O₃), which was isolated using semi-preparative Liquid Chromatography with high purity and structurally elucidated by HRMS and NMR, revealing cytotoxicity against HepaRG and MKN-1 cells versus the parent drug. The MET inhibitor Capmatinib, which is used for NSCLC, under forced degradation conditions produced three major degradation products—DP1- DP3—where Degradation Product-1 is formed by acid & base hydrolysis, DP2 and DP3 are formed by photolysis, and DP2 was isolated and confirmed by using the ¹H NMR with the stability-indicating UHPLC-Q-TOF-MS method developed.