Determination of 9 Elemental Impurities in Cefcapene Pivoxil Hydrochloride Granules by Inductively Coupled Plasma Mass Spectrometry

Due to the physical and chemical properties of cefcapene pivoxil and its granulars preparation containing many insoluble excipients, in order to accurately determine the contents of 9 elemental impurities (Cd, Pb, As, Hg, Co, V, Ni, Mo and Cr) in the cefcapene pivoxil hydrochloride granules, especially volatile element Hg, it was necessary to conduct complexation and stability treatment of the sample. 6 mL of nitric acid, 1.5 mL of hydrochloric acid and 0.1 mL of hydrofluoric acid were used as the digestion acid, and 50 mg of cefcapene pivoxil hydrochloride granules sample was digested by microwave at 180℃ for 30 min. After digestion, the acid was removed repeatedly, and then the volume of the sample solution for test was made up to 50 mL with mixed solution (volume ratio of 0.1:100) of hydrofluoric acid and hydrochloric acid-nitric acid-water at volume ratio of 1:4:95. Inductively coupled plasma mass spectrometry was used for the determination of 9 elemental impurities in the sample, and internal standard method was used for quantitative analysis. As shown by the results, linear relationships between values of mass concentration of 9 elemental impurities and response value ratio of analytes to internal standard were kept in definite ranges, with detection limits (3s/k) in the range of 0.001-0.070 μg·L^-1. RSDs of the determined values of 9 elemental impurities for 6 sample solutions with the same spiking amount were in the range of 2.9%-5.1%. Recovery test was made on substantial sample by standard addition method, giving results of recovery in the range of 82.0%-104%. This method has been applied to the analysis of substantial samples, the contents of 9 elemental impurities were all below the allowable concentration limits from guideline for elemental impurities.