Development of Different Separation Techniques for Impurity Profiling of Neostigmine Methylsulfate: A Comparative Study

Abstract

Abstract Different separation techniques have been employed to resolve mixtures of multicomponent preparations over the last few decades. They could be efficiently applied for impurity profiling of active drug substances. Impurity profiling has become a critical procedure in pharmaceutical companies to comply with numerous regulatory standards. Isolation and characterization of impurities are crucial for obtaining data that proves biological safety and efficacy. In this contribution, different HPLC, capillary electrophoresis (CE) and TLC-densitometric methods were developed for the determination of neostigmine methylsulfate (NEO) along with 3-hydroxyphenyltrimethyl ammonium methylsulfate (3-HPA) and 3-dimethylaminophenol (DAP) as its impurities in the presence of citric acid. The linearity for NEO was attained in the range of 5–120 μg/mL and 10–60 μg/mL for the HPLC and CE methods, respectively. Regarding the impurities, linearity was obtained over the range of 10–30 μg/mL for 3-HPA and 5–30 μg/mL for DAP in the two proposed methods. For the TLC method, NEO and DAP were determined within the range of 1–11 μg/band, whereas 3-HPA was assayed over the range of 2–12 μg/band. The suggested methods can be securely utilized for routine analysis of the cited components in quality control laboratories.