Determination of 25 Elemental Impurities in Staccato^® Loxapine Inhalation Powder by Inductively Coupled Plasma Mass Spectrometry with Microwave Digestion

To evaluate the risk of elemental impurities in Staccato^® loxapine inhalation powder samples, the contents of 25 elemental impurities （Cd, Pb, As, Hg, Co, V, Ni, Tl, Au, Pd, Ir, Os, Rh, Ru, Se, Ag, Pt, Li, Sb, Ba, Mo, Cu, Sn, Cr, and Fe） were simultaneously determined using the method mentioned by the title. The sample was taken and delivered to the dose uniformity sampling apparatus （DUSA tube） using a vacuum pump. After adding 10 mL of methanol to dissolve drugs, the methanol was evaporated at 80 ℃. Subsequently, 5 mL of nitric acid and 2 mL of hydrogen peroxide were added, and the mixed solution was digested at 190 ℃ for 30 min. The acid was removed by heating at 80 ℃ for 30 min, and the residue was diluted to 25 mL with the 5% （volume fraction） mixed acid solution （a mixture of nitric acid and hydrochloric acid at volume ratio of 4∶1）. Determination was performed using inductively coupled plasma mass spectrometry （ICP-MS） in collision mode with online internal standard method. It was shown that linear relationships between the mass concentrations of 25 elemental impurities and response value ratios of the target elements to internal standards were kept in definite ranges, with detection limits in the range of 0.007 00‒11.7 µg·L⁻¹. Repeatability （n=6）, intermediate precision （n=12）, and spike recovery tests were conducted on actual samples, giving RSDs of the determined values were 1.2%‒6.6% and 1.6%‒11%, respectively, and recoveries in the range of 72.0%‒108%, all of which complied with the requirements of USP〈233〉. The proposed method was applied to the analysis of 3 batches of samples, and detected amounts of 24 elemental impurities （excluding Fe） were all below the permissible limits calculated according to ICH Q3D.