注射用盐酸头孢甲肟丁基橡胶塞质量控制研究  

Quality Control of Butyl Rubber Stoppers of Cefmenoxime Hydrochloride for Injection

作　　者：郭胜才 席时东 戴安印 周文威[3] GUO Shengcail;XI Shidong;DAI Anyin;ZHOU Wenwei(No.903 Hospital of the Joint Logistic Support Force of PLA,Hangzhou,Zhejiang,China 310013;Ningbo Institute for Drug Control,Ningbo,Zhejiang,China 315000;The Second Hospital of Ningbo,Ningbo,Zhejiang,China 315010)

机构地区：[1]中国人民解放军联勤保障部队第九〇三医院,浙江杭州310013 [2]浙江省宁波市药品检验所,浙江宁波315000 [3]浙江省宁波市第二医院,浙江宁波315010

出　　处：《中国药业》2024年第4期68-72,共5页China Pharmaceuticals

基　　金：2018年国家药品抽检计划[食药监药化监(2017)131号]。

摘　　要：目的建立注射用盐酸头孢甲肟丁基橡胶塞的质量控制方法。方法以二氯甲烷-无水乙醇(1∶1,V/V)100℃水浴回流3.5 h处理胶塞,取续滤液。采用高效液相色谱法检测二硫化四甲基秋兰姆(简称秋兰姆)、2,6-二叔丁基-4-甲基苯酚(BHT)和单质硫,色谱柱为Shiseido CAPCELL PAK MGⅡC_(18)柱(250 mm×4.6 mm,5µm),流动相为1%三氟乙酸水溶液-乙腈(梯度洗脱),流速为1.0 mL/min,检测波长为280 nm,柱温为25℃,进样量为20µL。结果秋兰姆、BHT和单质硫的质量浓度分别在0.0002~0.0485µg/mL(r=0.9993)、0.46~230.67µg/mL(r=0.9999)和0.20~100.70µg/mL(r=0.9999)范围内与峰面积线性关系良好;精密度、稳定性试验结果的RSD均小于2.0%;平均加样回收率分别为58.22%,90.61%,104.46%,RSD分别为17.32%,5.58%,1.55%(n=9)。市场上抽取的16批空白丁基橡胶塞样品中BHT与单质硫的含量分别为0~169.88µg/g和0~102.79µg/g,均未检出秋兰姆。29批注射用盐酸头孢甲肟粉末样品中,BHT含量为0~36.61µg/g,且均未检测到单质硫和秋兰姆;包材胶塞中,BHT含量为0~125.64µg/g,单质硫的含量为0~79.93µg/g,均未检出秋兰姆,60℃下倒置5 d后与20℃及以下(阴凉库)放置比较,BHT含量无显著变化(P>0.05),单质硫含量显著减少(P<0.05)。结论所建立的方法操作简便、结果准确,可用于药用丁基橡胶塞中秋兰姆、BHT和单质硫的含量测定及注射用盐酸头孢甲肟的质量控制。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 MGⅡC_(18) column(250 mm×4.6 mm,5µm),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 20µL.Results The linear ranges of thiuram,BHT and elemental sulfur were 0.0002-0.0485µg/mL(r=0.9993),0.46-230.67µg/mL(r=0.9999)and 0.20-100.70µg/mL(r=0.9999)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 169.88µg/g and 0 to 102.79µg/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 36.61µg/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 125.64µg/g and 0 to 79.93µg/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 stop

关 键 词：注射用盐酸头孢甲肟 药用丁基橡胶塞 高效液相色谱法 二硫化四甲基秋兰姆 2 6-二叔丁基-4-甲基苯酚 单质硫 含量测定 

分 类 号：R927.1[医药卫生—药学] R917