Strategies for the Investigation, Synthesis, and Characterization of Process-Related Impurities in Anti-Parkinson Drug Selegiline Hydrochloride

Abstract: Impurities are a crucial part of active pharmaceutical ingredient (API), even though they haven't been contemplated in the pharmacological evaluation of the Benefit-Risk information. Consequently, there's a need to discover their origin, and managing them in the drug substance is vital throughout process development and optimization. Research has been performed to assess the process- related impurities stemming from raw material or key starting material attributes. This article describes the identification, synthesis, and regulation of diverse processes and raw material-related facets, including both known and unknown impurities, noted during the process development and optimization of Selegiline hydrochloride. Based on high-performance liquid chromatography (HPLC) verification of process-related impurities and examination of the synthetic route of Selegiline hydrochloride, the structures were illustrated for process-related impurities and the investigation of the synthetic pathway of Selegiline hydrochloride. We synthesized four process-related impurities, and their structures were identified using various spectroscopic tools, like ¹H NMR, ¹³C NMR, and Mass spectrometry. Here, we report the synthesis of four process-related impurities, comprising Selegiline EP impurity G (Z-isomer), Selegiline EP impurity G (E-isomer), Selegiline EP impurity D, and impurity 3, which were successfully controlled during the industrial-scale production of Selegiline hydrochloride.