Background: To control the quality of various butyl rubber closures and assess their applicability to cefamandole nafate, HPLC/ GC-MS methods were developed to qualitatively and quantitatively analyze the organic components in various types of butyl rubber closures and drug powder of cefamandole nafate for injection, and migration of these components from rubber closures to drug also were studied. background: To control the quality of various butyl rubber closures and assess their applicability to cefamandole nafate, HPLC/ GC-MS methods were developed to qualitatively and quantitatively analyze the organic components in various types of butyl rubber closures and drug powder of cefamandole nafate for injection, and migration of these components from rubber closures to drug also were studied. Materials and Methods: The chemical components in the rubber closures and corresponding drug were identified by GC-MS in full scan mode and NIST mass library. A GC-MS method in SIM mode was established to quantitatively analyze siloxane compounds, aromatic hydrocarbons and saturated chain-hydrocarbons in rubber closures and drugs. An HPLC method was established to quantitatively analyze antioxidants and sulfides from rubber closures and drugs. The turbidity values of powder for injection were measured by a turbidimeter. Further, the correlation between the content of organic components in the drug and the clarity of the solution was analyzed. objective: To control the quality of various butyl rubber closures and assess their applicability to cefamandole nafate Results: It was found that the chemical components were released from butyl rubber closures and migrated to the drug, which influenced solution clarity of cefamandole nafate for injection and was the main factor to cause solution turbidity of powder for injection. The gradual migration of components occurred over time with the use of common butyl rubber closures, but the coated butyl rubber closures (rubber plated with membrane) were coated with a polytetrafluoroethylene film to block the contact between rubber closures and the drug, and could effectively prevent the migration of the components from rubber closures to drugs. The organic components in the butyl rubber closures were mainly identified as siloxanes, saturated chain-hydrocarbons, and antioxidants. An unknown ingredient was identified as 1-piperidinecarboxaldehyde, and trace amounts of toxic toluene were also detected within limits. method: The chemical components in the rubber closures and corresponding drug were identified by GC-MS in full scan mode and NIST mass library. A GC-MS method in SIM mode was established to quantitatively analyzed siloxane compounds, aromatic hydrocarbons and saturated chain-hydrocarbons in rubber closures and drugs. A HPLC method was established to quantitatively analyze antioxidants and sulfides from rubber closures and drugs. The turbidity values of powder for injection were measured by turbidimeter. Further, the correlation between the content of organic component in the drug and the clarity of solution was analyzed. Conclusion: It is suggested that rubber plated with membrane or rubber closures of high quality were applicable to cefamandole nafate for injection and should be used in its production. HPLC/ GC-MS methods can be used as an effective method for quality control of butyl rubber closures and compatibility research with drugs to ensure drug safety for the public.

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 À1 . 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, Mg 2+ , and Cu 2+ 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.Bingyong Xu and Jiarui Gao contributed equally to this article.

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