Objective To establish a quality control method for butyl rubber stoppers of Cefmenoxime Hydrochloride for Injection.Methods Rubber stoppers were treated with dichloromethane-anhydrous ethanol(1∶1,V/V)refluxed in water bath(100℃)for 3.5 h,the filtrate was collected.High-performance liquid chromatography(HPLC)method was used to detect tetramethylthiuram disulfide(referred to as thiuram),butylated hydroxytoluene(BHT)and elemental sulfur.The chromatographic column was the Shiseido CAPCELL PAK MGⅡ C18 column(250 mm×4.6 mm,5 µm),the mobile phase was 1%trifluoroacetic acid aqueous solution-acetonitrile(gradient elution),the flow rate was 1.0 mL/min,the detection wavelength was 280 nm,the column temperature was 25℃,and the injection volume was 20 µL.Results The linear ranges of thiuram,BHT and elemental sulfur were 0.000 2-0.048 5 µg/mL(r = 0.999 3),0.46-230.67 µg/mL(r = 0.999 9)and 0.20-100.70 µg/mL(r = 0.999 9)respectively.The RSDs of precision and stability tests were lower than 2.0%.The average recovery rates of the above three ingredients were 58.22%,90.61%,104.46%,with RSDs of 17.32%,5.58%,1.55%respectively(n = 9).The content of BHT and elemental sulfur in 16 batches of blank butyl rubber stoppers from the market was in the range of 0 to 169.88 µg/g and 0 to 102.79 µg/g respectively,and no thiuram was detected.The content of BHT in the 29 batches of Cefmenoxime Hydrochloride for Injection powder was in the range of 0 to 36.61 µg/g,and no elemental sulfur or thiuram was detected;the content of BHT and elemental sulfur in the packaging rubber stoppers was in the range of 0 to 125.64 µg/g and 0 to 79.93 µg/g respectively,and no thiuram was detected;compared with that at 20℃and below(microtherm warehouse),the BHT content showed no significant change after inversion at 60℃for 5 d(P>0.05),while the elemental sulfur content significantly decreased(P<0.05).Conclusion The established method is easy and accurate,which can be used for the determination of thiuram,BHT and elemental sulfur in pharmaceutical butyl rubber stoppers,as well as the quality control of Cefmenoxime Hydrochloride for Injection.
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