홍성철 (Thermo Fisher Scientific)

홍성철 (Thermo Fisher Scientific)

홍성철 (Thermo Fisher Scientific)

이정향 (Thermo Fisher Scientific)

권한순 (Thermo Fisher Scientific)

Detecting and identifying drug substance impurities and degradation products is a crucial issue of pharmaceutical research and development. Due to the complexity of drug products, which often consist of multiple mixtures, accurately detecting and identifying these impurities can be challenging. High-resolution accurate mass (HRAM) mass spectrometer (MS) is commonly applied for elucidating the structure of active pharmaceutical ingredient (API) impurities because of its sensitivity, selectivity, and ability to determine elemental composition and acquire fragmentation spectra. However, many established methods for impurity profiling and stability indication use buffer systems that are incompatible with MS. This incompatibility can be problematic when new or unknown impurities arise due to changes in raw materials or process modifications, as replacing these buffer systems with MS-compatible alternatives can alter both retention times (RT) and the retention order of chromatographic peaks. Moreover, even when LC methods with MS-compatible eluents are validated for established APIs, direct interfacing with MS can be challenging due to high flow rates (>1 mL/min) and broad peak shapes. To address these issues, a Trap Heart-Cut 2D-LC system can be used to concentrate impurities for LC/MS detection. This study demonstrates the application of a Trap Heart-Cut 2D-LC system to online modulate the eluent system of a 1D HPLC method that is incompatible with MS, facilitating its connection to HRAM MS. This approach was successfully employed to identify impurities in rabeprazole, a proton pump inhibitor used to treat gastroesophageal reflux disease.​