Research on Compatibility of Packaging Materials of High-Risk Cephalosporin Powder Injection and Establishment of Indicator Component Evaluation Method

Abstract

aims: To establish a GC-MS method for the determination of extractable substances in the stoppers of Ceftriaxone sodium bottles for injection; To establish a HPLC method for the determination of vulcanizing agent and antioxidant in Ceftriaxone sodium for injection bottle stopper and to analyze the correlation between the volatile substances of rubber stopper and the clarity of solution. objective: To establish a GC-MS method for the determination of extractable substances in the stoppers of Ceftriaxone sodium bottles for injection; To establish a HPLC method for the determination of vulcanizing agent and antioxidant in Ceftriaxone sodium for injection bottle stopper and to analyze the correlation between the volatile substances of rubber stopper and the clarity of solution. method: GC-MS method was used with capillary column Rtx-5MS (30.0 m×0.25 mm, 0.25 µm), the carrier gas was He at the flow rate of 1.8mL·min-1, the temperature of injection port was 200 ℃, shunt ratio was 10∶l, the column temperature was programmed temperature(initial column temperature was 40 ℃ and kept for 15 min, and with the speed of 10 ℃ upping to 100 ℃ and kept for 2 min, and with the speed of 25 ℃ upping to 230 ℃ and kept for 10 min), the interface temperature was 250 ℃, and the scanning range was from 29 to 600(m·z-1), and the volatile substances were using full scan. An inertsil ODS-3 column(250 mm×4.6 mm, 5 µm) was used for the HPLC analysis. The mobile phase A consisted of water containing 0.04% trifluoroacetic and the mobile phase B consisted of acetonitrile containing 0.04% trifluoroacetic acid, the gradient elution was used and the flow rate was set as 1.0 mL·min-1. The column temperature was 30 ℃, the detection wavelength was 210 nm and the injection volume was 10 µL. result: Antioxidant BHT(264), silicone oil and other organic compounds in rubber stopper permeated and migrated to the sample with acceleration time by GC-MS. A good linearity was observed over the range of 0.5-100 μg·mL-1(r＞0.999). The detection limits of vulcanizing agent and antioxidant were about 0.03 μg·mL-1, and the quantitation limits were about 0.1 μg·mL-1. The average recoveries (low, medium and high) of antioxidant (168, 264, 330, 1076, 1010) and vulcanizing agents (carbon disulfide, sulfur) were between 90.0% and 110.0%, and the corresponding RSD were less than 5% (n=9) by adding standard recovery experiments. The stability test showed that the antioxidant and the vulcanizing agent solution had good stability and was stable within 24 hours. conclusion: the GC-MS/HPLC method can be used for the quality control of rubber stopper of cefuroxime Sodium for Injection.The compatibility study and comprehensive evaluation system of Ceftriaxone sodium for injection packaging materials have been initially formed.