Analysis of Organic Components in Various Butyl Rubber Closures and their Compatibility Study with Cefamandole Nafate by HPLC/GC-MS
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. 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. 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.
危险品化学品经营许可证（带存储）