Migration and Determination of Chloride in the Chlorinated Butyl Rubber Stopper for Freeze-Dried Powder Injections

Abstract

In this study, the migration and determination method of chloride in the chlorinated butyl rubber stopper for freeze-dried powder injections by ion chromatography was established. It investigated the chloride leaching levels. The inorganic anions were separated by IonPac AS 11-HC column and IonPac AS 11-HC guard column with potassium hydroxide solution as gradient eluent. The device was equipped with an AERS 500 (4.0 mm) anion suppressor. The conductivity detector was applied to analysis. The conductivity detector current was 87 mA. The temperature of ion chromatography column was 30°C. The column flow rate was 1.0 mL/min. The chloride had a good liner relationship (r=0.9999) in the range of 0.2 mg/L-20.0 mg/L. The LOD and LOQ of this method were 0.005 mg/L and 0.02 mg/L, respectively. The chlorinated butyl rubber stopper was extracted by 30% isopropanol aqueous solution at 70°C for 6 days. The samples concentration of chlorides ranged from 178 mg/kg-430 mg/kg.