Determination of elemental impurities in lomefloxacin hydrochloride ear drops by inductively coupled plasma-mass spectrometry using oxygen reaction mode and study of their catalytic effect on photodegradation reaction

Abstract

Rationale: This study developed a method for the simultaneous determination of 12 element impurities in lomefloxacin hydrochloride ear drops using inductively coupled plasma-mass spectrometry (ICP-MS) in accordance with the requirements of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Q3D. However, this product contains high concentrations of organic compounds such as glycerol and ethanol, and soluble carbon interference exists when it is determined by direct injection method. Therefore, we applied ICP-MS using oxygen reaction mode to reduce the effect of high organic matter on plasma body. The catalytic effect of trace metal ions on the photodegradation of lomefloxacin hydrochloride was also investigated.

Methods: The sample was dissolved, diluted, and directly determined by direct injection using oxygen reaction mode of ICP-MS with ⁴⁵ Sc, ⁷³ Ge, and ¹¹⁵ In as internal standards. Direct injection using oxygen reaction mode was equipped with argon-oxygen mixer. To investigate the catalytic effect of metal ions on photodegradation, a series of combinations of lomefloxacin hydrochloride mixed with different metal ions were designed. After being irradiated under ultraviolet light for 10 days, the photodegraded impurities in combinations were determined using high-performance liquid chromatography.

Results: The linear relationships in the corresponding concentration range for 12 element impurities were good (r > 0.9993). Limits of detection were between 0.002 and 1.294 ng ml^-1 . The average recoveries were 93.7%-108.2%, and the precision relative standard deviation was 0.04%-0.55% (n = 6). The experimental results showed that metal ions had a certain catalytic effect on photodegradation of lomefloxacin when EDTA, Mg²⁺ , and Cu²⁺ coexisted.

Conclusions: ICP-MS using oxygen reaction mode is suitable for the direct determination of the sample rich in organic matter without digestion and can effectively eliminate the interference of high organic matter in this product. The established method was rapid, sensitive, and accurate and can be used for the quality control of elemental impurities in lomefloxacin hydrochloride ear drops.