药用丁基胶塞中抗氧剂-BHT和硫化剂-可提取硫的测定

目的：建立药用丁基橡胶塞中添加剂［抗氧剂264（2，6-二叔丁基-4-甲基苯酚，简称BHT）和硫化剂可提取硫］的含量测定方法。方法：以二氯甲烷-无水乙醇为提取溶剂，利用高效液相色谱法对药用丁基橡胶塞的BHT和可提取硫含量进行测定，以含0.1%三氟乙酸的乙腈-含0.1%三氟乙酸的水（90∶10）为流动相，流速1.0 mL·min^-1，检测波长280 nm。结果：抗氧剂BHT的线性检测范围0.41~103.00μg·mL^-1（r²=1.000），可提取硫的线性检测范围0.10~103.50 μg·mL^-1（r²=0.999 9），BHT和可提取硫的平均回收率分别为95.2%和86.8%。测定7批药用胶塞中BHT与可提取硫含量范围分别为4~206 μg·g^-1和1~143μg·g^-1。结论：本文建立的检测方法经方法学验证，可用于考察药用丁基橡胶塞中BHT和可提取硫的含量及质量控制。

Objective: To establish a method for determination of the additives[antioxidant 264(2, 6-di-tertbutyl-4-methylphenol,hereinafter referred to as BHT) and vulcanizing agent (extractable sulphur)]in medicinal butyl rubber. Methods: Dichloromethane-ethanol was adopted as the extraction solvent,and the HPLC was used for determination of BHT and extractable sulphur in medicinal butyl rubber. The mobile phase consisted of acetonitrilewater (90:10,containing 0. 1%TFA). The flow rate was 1. 0 mL·min^-1. The detection wavelength was 280 nm. Results: The linearity ranges wer from 0. 41 to 103. 00 μg·mL^-1 (r²=1. 000) and 0. 10 to 103. 50 μg·mL^-1 (r²=0. 999 9) for BHT and extractable sulphur. The average recoveries of BHT and extractable sulphur were 95. 2% and 86. 8%,respectively. The determination results of BHT and extractable sulphur sulphur in seven batch rubbers were 4-206 μg·g^-1 and 1-143 μg·g^-1 respectively. Conclusion: The validated method established in this article can be used for the assay of BHT and extractable sulphur content and for its quality control in medicinal butyl rubber.

[1] XIAO BM, GOZO SK, HERZ L. Development and validation of HPLC methods for the determination of potential extractables from elastomeric stoppers in the presence of a complex surfactant vehicle used in the preparation of parenteral drug products[J]. J Pharm Biomed Anal,2007, 43(2):558
[2] CORREDOR CC, HABY TA. Comprehensive determination of extractables from five different brands of stoppers used for injectable products[J]. PDA J Pharm Sci Technol,2009, 63(6):527
[3] LACHMAN L,URBNYI T,WEINSTEIN S. Stability of antibacterial preservatives in parenteral solutions Ⅳ:contribution of rubber closure composition on preservative loss[J]. J Pharm Sci,1963, 52(3):244
[4] 李涛,赵声兰,余旭亚,等.抗氧化剂的研究与应用现状[J].食品研究与开发, 2003, 24(2):23 LI T, ZHAO SL, XU XY, et al. The status of research and application of antioxidant[J]. Food Res Dev, 2003, 24(2):23
[5] 21 CFR, Part 210&211, Subpart E(211. 94), Drug Product Containers and Closures[S]. 1997:11
[6] 王华英,张隐峰,应俊扬.萃取-气相色谱法测定顺丁橡胶中抗氧剂264含量[J].橡胶科技, 2013, 11(3):42 WANG HY, ZHANG YF, YING JY. Detection of antioxidant 264 content in butadiene rubber by extraction-gas chromatography[J]. Rubber Sci Technol,2013, 11(3):42
[7] FDA. Inactive Ingredients Database[DB/OL]. 2016[2016-3-26]. http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm
[8] EP 7. 0[S]. 2011:342
[9] 苏立伟,曲甍甍,吴笛,等.酚类化合物对不同组织细胞DNA损伤的研究[J].环境化学, 2003, 22(4):390 SU LW, QU MM, WU D, et al. Study on DNA damage of several different biomaterials induced by hydroxybenzene compounds[J]. Environ Chem,2003, 22(4):390
[10] 姚世杰,樊云峰.橡胶硫化剂进展[J].中国橡胶,2003,21(19):23 YAO SJ, FAN YF. Development on rubber curing ingredients[J]. China Rubber,2003,21(19):23
[11] 李樾,杨会英,王峰,等.药用卤化丁基橡胶塞中可提取硫的检测研究[J].中国药事,2014, 28(11):1257 LI Y,YANG HY,WANG F,et al. Study on detection of extractable sulphur from medicinal halpgenated butyl rubber[J]. Chin Pharm Aff, 2014, 28(11):1257
[12] 王飞,司俊杰.丁基橡胶药用瓶塞配方硫化体系对头孢唑啉钠相容性的影响研究[J].机电信息, 2005(1):27 WANG F, SI JJ. Study on influence of compatibility between butyl medicinal rubber vulcanizing system and cefazolin sodium[J]. Mech Electr Inf,2005(1):27
[13] 郭舜华.硫化体系及工艺对丁基瓶塞与生理盐水相容性的影响[J].中国橡胶, 2006, 22(3):26 GUO SH. The influence on the compatibility between butyl bottle cork and physiological saline from vulcanizing system and technology[J]. China Rubber, 2006, 22(3):26
[14] YBB00142002-2015药品包装材料与药物相容性试验指导原则[S]//国家药包材标准. 2015:381 YBB00142002-2015 Guidelines of evaluating compatibility between pharmaceutical packaging and pharmaceuticals[S]//Quality Standards for Drug Packaging Meterials. 2015:381