OBJECTIVE  To establish a method for simultaneously determining the content of 14 elemental impurities in the aluminum chloride hexahydrate and to conduct a risk assessment.

METHODS  An internal standard method using inductively coupled plasma mass spectrometry was employed. Elements Te, Sc, Ge, In, and Bi were used as internal standards. The standard addition method was applied, with samples diluted and directly injected. The contents of 14 elemental impurities in 8 batches of samples were determined(including Class 1 elements: Cd, Pb, As, Hg; Class 2A elements: Co, V, Ni; Class 3 elements: Li, Sb, Ba, Mo, Cu, Sn, Cr). A risk assessment was conducted based on the ICH Q3D guidelines for the permitted daily exposure(PDE) of these elements for oral, injectable, and inhalation routes of administration.

RESULTS  Each element demonstrated a good linear relationship within the respective concentration range(r≥0.9993). The precision test had an RSD of less than 4.3%, the repeatability test had an RSD of less than 7.8%, and the spike recovery rate ranged from 93.9% to 111.9%, with an RSD of 2.3% to 7.8%(n=9). Elevated levels of Ni, V, Li, and Cr were observed in a subset of samples, exceeding the inhalation PDE limits but remaining within the safer limits established for injectable and oral administration.

CONCLUSION  This method is simple, rapid, and accurate, and can be used for the simultaneous determination of elemental impurities in crystalline aluminum chloride. Enterprises should pay attention to the actual use of excipients and specific routes of administration. Excipient manufacturers should undertake necessary raw material screening, process control, and process improvements.