Surface analysis of sodium metamizolate as an active pharmaceutical ingredient in solid form

This study focuses on the surface and subsurface characterization of a pharmaceutical tablet containing sodium metamizolate (NaMET), with an emphasis on mass spectrometry using time-of-flight secondary ion mass spectrometry (ToF-SIMS). ToF-SIMS enabled the identification of NaMET-specific fragment ions, which served as signals for the determination of the spatial distribution of this active pharmaceutical ingredient (API) within the tablet matrix. A ToF-SIMS fragmentation mechanism for NaMET was proposed based on the ToF-SIMS spectra analysis measured on a NaMET reference standard. 3D ToF-SIMS imaging showed heterogeneous localization of the API across a 5 μm depth. Complementary techniques, including 3D profilometry and atomic force microscopy (AFM), provided surface roughness and morphological data, while X-ray photoelectron spectroscopy (XPS) confirmed the elemental composition and chemical states. Depth profiling by XPS further supported the non-uniform distribution of NaMET. • ToF-SIMS fragmentation mechanism was proposed for NaMET. • ToF-SIMS reveals 3D spatial distribution of NaMET in pharmaceutical tablets. • Depth profiling links NaMET localization to formulation-driven surface features. • Combined ToF-SIMS/XPS approach enhances surface chemical characterization. • ToF-SIMS identifies NaMET fragment ions for API mapping in complex matrices.