Structure elucidation and confirmation of unknown impurities in an animal health product by the strategy of utilizing a variety of advanced analytical techniques

Abstract

During stability test of an animal health finished drug product (liquid transdermal formulation packed in plastic syringe), several unexpected peaks were observed in the HPLC chromatograms. The structure and possible origin of these unknown peaks needed to be determined to ensure the safety and efficacy of the finished drug product. Each unknown peak poses different analytical challenges for full structure elucidation. In this paper, we presented the strategies and experimental results for the identification of these unexpected peaks using a combination of different advanced analytical techniques, namely HPLC/PDA, High Resolution MS and MS2, and headspace GC/MS. The orthogonal information provided by UV spectra, HRMS data, elemental composition, and MS2 fragmentation of these unknown peaks were used to propose the most probable structures for these unknown peaks. The proposed structures of these unknown peaks were fully confirmed by reference materials. The origins of these compounds were identified through an extraction study of the primary packaging materials. Hence, the unknown peaks were confirmed as leachable compounds from the primary packaging materials. Successful identification of these compounds enables quantification and toxicological evaluation. Additionally, the identification of these leachable compounds can be used to improve the primary package production process. By minimizing or eliminating the use of these compounds in the package production process, the risk of these compounds migrating into final finished drug product will be minimized in the future.