Design Synthesis and Structural Elucidation of Novel Impurities in Selected Active Pharmaceutical Ingredients of Bulk Drugs Baricitinib Venetoclax and Erlotinib

Abstract

The discovery and synthesis of impurities in Active Pharmaceutical Ingredient (API) molecules newlineare critical for assuring drug safety, quality, and regulatory compliance. Impurities might come newlinefrom the initial ingredients, intermediates, side reactions, degradation processes, or residual newlinesolvents. Their presence, even in small amounts, can have an impact on the efficacy and safety newlineof the finished drug product. Regulatory requirements, such as ICH Q3A and Q3B, mandate newlinethe detection and qualification of contaminants that exceed particular criteria, emphasizing the newlineimportance of rigorous analytical and synthetic techniques. The main objective of this thesis is newlineidentification and synthesis of API molecules available in the current drug market. We mainly newlinefocused on Baricitinib, Venetoclax and Erlotinib. Baricitinib Lactone (BCL), Baricitinib dimer newline(BCD), Baricitinib hydroxy methyl (BHM) impurities were identified as synthetic impurities newlineof Baricitinib. Oxidative degradation studies of Venetoclax lead to the identification of newlineVenetoclax N-Oxide (VNO) Venetoclax hydroxyl amine (VHA) impurities. Similarly, 6,7-O- newlineDidesmethyl erlotinib (DP-1), Erlotinib dihydroxy impurity (DP-2), 7-O-desmethyl erlotinib newline(DP-3), and 6-O-desmethyl erlotinib (DP-4) were identified as the acidic degradation products newlineof Erlotinib. newlineChapter-1 Introduction newlineChapter-2 4.1 Isolation, Synthesis and Characterization of Novel Synthetic Impurities of newlineBaricitinib newlineChapter-3 2. Synthesis and Characterization of unique oxidative impurities of Venetoclax newlineincluding Meisenheimer rearrangement product newlineChapter-4 3. Identification and synthesis of unprecedented acid-induced degradation newlineproducts of Erlotinib newlineChapter-5 Summary and Future Works. newline newline