RESUMEN
During the trial production of Armillarisin A for injection (AA-I), unidentified needle-like yellow-brown crystals were occasionally observed. Here, we report an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS) method for determining the source of the visible foreign bodies in the formulations of Armillarisin A active pharmaceutical ingredient (AA-API). AA-API, photolyzed samples, the intermediate polymer, and the excipient analyzed determined after the separation on a Waters Symmetry C18 (3.5 µm, 4.6 × 75 mm) column with a mobile phase consisting of a methanol/acetic acid (0.1 mol/L) aqueous solution (50:50). Furthermore, the crystal type of the visible foreign bodies, the intermediate polymer and AA-API were investigated by X-ray powder diffraction (XRD). The results revealed that the characteristics of the visible foreign solids were the same as those of AA-API as regards UPLC peak position (368 nm) and MS spectrum in negative ion detection mode. The visible foreign solids were thus identified as unpolymerized crystals of AA-API and were attributed to AA-API itself. The results showed that the production process could be improved by changing the stirring method and frequency as well as by optimizing the polymerization temperature to ensure the safety, stability, and control of the product quality in the stage of batch production.