Detection and Characterization of an Unknown Impurity in Levothyroxine Oral Solution Product: Implications for Formulation Development and Storage

Abstract

An existing USP(2010) impurity method for levothyroxine drug substance was modified to expand its applicability for the analysis of levothyroxine oral solution (OS) formulation while achieving desirable resolution between the components of OS formulation. When analyzed using modified USP(2010) method, an unknown impurity was detected in one of the levothyroxine OS products. A systematic investigation of unknown impurity was carried out using a combination of chromatographic, mass spectral and physicochemical methods to understand the nature of this unknown impurity. A possible elucidation of chemical structure and reaction mechanism for the formation of this previously unreported impurity was proposed.

Keywords: Characterization; De-amination; De-iodination; LC-MS; Levothyroxine; Levothyroxine oral solution; Oral solution formulation; Parabens; Preservatives; Thyronine; Unknown impurity.