药用丁基胶塞---四大药典检测标准异同

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药用丁基胶塞规格标准

药用丁基胶塞规格标准

药用丁基胶塞的规格标准可能包括:
尺寸:通常为圆柱形,直径为12mm-36mm,长度为3mm-12mm。

压缩密度:应符合《中华人民共和国药典》或《中国药典》标准。

湿润度:应符合《中华人民共和国药典》或《中国药典》标准。

弹性:应符合《中华人民共和国药典》或《中国药典》标准。

粘度:应符合《中华人民共和国药典》或《中国药典》标准。

断裂强度:应符合《中华人民共和国药典》或《中国药典》标准。

包装:应符合国家药品监管部门的要求,应该是密封包装并且有标签和说明书。

请注意,这些标准可能会不时变更,并可能受到药品类别和用途的限制。

丁基橡胶药用瓶塞检测SOP

丁基橡胶药用瓶塞检测SOP

丁基橡胶药用瓶塞检测SOP1. 目的为规范注射液用卤化丁基橡胶药用瓶塞的检定,特制定本SOP。

2. 范围本SOP适用于直接与注射剂接触的卤化丁基橡胶塞(注射液用卤化丁基橡胶塞、预灌封注射器用氯化丁基橡胶塞、预灌封注射器用溴化丁基橡胶塞)的检定。

3. 定义无4. 职责4.1.QC负责本规程的起草、修订、培训及执行。

4.2.QA、QC组长、质量管理部经理负责本规程的审核。

4.3.质量总监负责批准本规程。

4.4.QA负责本规程执行的监督。

5. 引用标准5.1.注射液用卤化丁基橡胶塞国家食品药品监督管理局直接接触药品的包装材料和容器标准汇编5.2.预灌封注射器用氯化丁基橡胶活塞国家食品药品监督管理局直接接触药品的包装材料和容器标准汇编5.3.预灌封注射器用溴化丁基橡胶活塞国家食品药品监督管理局直接接触药品的包装材料和容器标准汇编5.4.《中华人民共和国药典》6. 材料6.1.仪器设备天平,恒温水浴箱,分光光度计,pH计,恒温干燥箱,变温电炉,干燥器,电导率仪,高温炉。

6.2.试剂溶液标准铅溶液:购入;氯化铵铵溶液:取氯化铵10.5g,加水溶解使成100ml,即得;标准锌溶液:称取硫酸锌(ZnSO4·7H2O)0.440g,置1000ml量瓶中,加水溶解并稀释至刻度,摇匀,即得(每1ml相当于100µg的Zn);0.02mol/L高锰酸钾滴定液: 按《高锰酸钾滴定液配制及标定SOP》操作;0.1mol/L硫代硫酸钠滴定液:按《硫代硫酸钠滴定液配制及标定SOP》操作;碳酸氢钠:购入;硝酸:购入;硝酸银试液:取硝酸银17.5g,加水适量使溶解成1000ml,摇匀,即得;0.1%氯化钾溶液:取氯化钾0.1g,加水使溶解成100 ml,即得;稀硫酸:取硫酸57ml,加水稀释至1000ml,即得;淀粉指示液:取可溶性淀粉0.5g,加水5ml搅匀后,缓缓倾入100ml沸水中,随加随搅拌,继续煮沸2min,放冷,倾取上层清液,即得,本液应临用新制;碱性碘化汞钾试液:二氯化汞饱和水溶液:取二氯化汞7g,溶于100ml水中,摇匀。

药用丁基胶塞质量标准

药用丁基胶塞质量标准

药用丁基胶塞质量标准药用丁基胶塞质量标准药用氯化丁基橡胶塞标准(试行)YBB 00042002本标准适用于直接与注射剂接触的氯化丁基橡胶塞。

【外观】取本品数个,目视检测,表面色泽应均匀,不得有污点、杂质、气泡、裂纹、缺胶、粗糙、胶丝、胶屑、海绵状、毛边;不得有除边造成的残缺或锯齿现象;不得有模具造成的明显痕迹。

【鉴别】(1)称取本品5~20g,置于干燥的试管中,将长约4毫米的钠片一片置于固定并倾斜的试管中,使其恰好位于试样之上,用火焰的尖端加热试管,将钠融化在试样上,继续加热2分钟,使呈深红色,冷却后加入乙醇,将过剩的钠醇化,加水约10ml溶解,过滤,滤液备用。

A:取滤液1.5ml置于试管中,加硝酸酸化,煮沸1~2分钟,加入硝酸银1滴,应产生白色沉淀。

B:取滤液0.2ml,置于微量试管中,加氯仿1滴,加稀硫酸1滴,加薪配置的氨水1滴(或3%H2O2溶液2~3滴),经振荡混匀后,静止5分钟,氯仿层应不显色。

(2)红外光谱取本品约3g切成3m m×3mm小块置索氏抽提器中用丙酮或适宜的溶剂回流浸提8小时,取残渣80℃烘干,取0.1~0.2g置于裂解管的底部,然后用试管夹水平的将裂解管移到酒精灯上加热,当出现裂解产物冷凝在裂解管冷端时,再继续加热至裂解基本完全但没碳化为止,取少许裂解物滴在溴化钾片上,在80℃烘干,照分光光度法(《中华人民共和国药典》2000年版二部ⅣC)测定,应与对照图谱基本一致。

【穿刺落屑】输液瓶用胶塞:取10只被测胶塞和10只已知穿落屑数的胶塞分别装在与其相配的输液瓶上,每只瓶中注入半瓶水。

加上铝盖,用手动封盖机封口,打开铝盖穿刺部位。

按先被测胶塞再已知穿刺落屑数胶塞的顺序交替穿刺胶塞。

穿刺时,胶塞保持直立,握持金属穿刺器(见图1)垂直向胶塞标记区域内穿刺,晃动数秒后拨出穿刺器。

每次穿刺前用丙酮或甲基—异丁基酮擦拭穿刺器。

穿刺器不得有损坏,并保持锋利(如穿器损坏,须换用新的)。

药用丁基胶塞

药用丁基胶塞

药用丁基胶塞的使用安全性药用丁基胶塞的生产背景丁基橡胶瓶塞的内在洁净度、化学稳定性、气密性、生物性能都很好,但是因配方复杂及所加原材料浓度梯度的关系,与一些分子活性比较强的药物封装后,被药物吸收、吸附、浸出、渗透,产生了胶塞与药物的相容性问题,比较突出的是部分头孢菌素类、部分大输液类、以及较多中药注射液制剂等。

所以通过选用一种惰性柔软涂层,覆盖在胶塞表面,隔离药品与橡胶瓶塞的直接接触,这样可以明显改善与药物的相容性。

国家至2004年底前所有药用胶塞(包括输液、口服液等各剂型用胶塞)一律停止使用普通天然胶塞;所有药厂的药品橡胶塞都要使用丁基胶塞。

药品是一种特殊的商品, 其药效与质量直接关系到人身健康和安全, 药品包装的材料与结构形式, 尤其是直接接触药品的包装材料, 对保证药品稳定性起决定性作用。

不适宜的包装材料可引起活性药物成分的渗出、吸附, 甚至发生化学反应, 导致药品失效, 有时还会产生严重的毒副作用。

因此, 药包材的选择是否合适, 是评价药品质量的一项重要指标,丁基胶塞具有吸湿率低, 化学性好, 气密性好, 无生理毒副作用等显著特点, 特别适宜于用作药品密封。

因此天然胶塞已列入被淘汰之列, 而用丁基胶塞取代。

丁基橡胶是由异丁烯和少量异戊二烯(≤3 %)在超低温(- 95 ℃) 条件下聚合而成的共聚物[ 3] ,为白色或暗灰色透明性弹体,其结构式可用下列通式表示:丁基橡胶是气密性最好的橡胶, 其气体透过率约为天然橡胶的1 /20 , 丁基橡胶的耐热性、耐候性和耐臭氧氧化性都很突出。

最高使用温度可达200 ℃, 能长时间暴露于阳光和空气中而不易损坏。

丁基橡胶耐化学腐蚀性好, 耐酸、碱和极性溶剂。

此外, 丁基橡胶的电绝缘性和耐电晕性能比一般合成橡胶好。

耐水性能优异, 水渗透率极低。

减震性能好, 在- 30 ~50 ℃具有良好的减震性能。

在玻璃化温度(- 37 ℃) 时仍具有屈挠性。

丁基橡胶的缺点是硫化速度很慢, 需要高温或长时间硫化, 自黏性和互黏性差, 与其它橡胶的相容性差, 难以并用[ 4] 。

药用丁基胶塞化学助剂检测及与药物相容性研究进展

药用丁基胶塞化学助剂检测及与药物相容性研究进展

药用丁基胶塞化学助剂检测及与药物相容性研究进展
随着医疗技术的不断发展,药物包装材料的质量和安全性越来越受到关注。

作为一种常用的药物包装材料,丁基胶塞的安全性和药物相容性也备受关注。

为了确保药物的质量和安全性,需要对丁基胶塞的化学助剂进行检测,并研究其与药物的相容性。

丁基胶塞的化学助剂包括硫化剂、防老剂、活性剂等。

其中,硫化剂是使丁基胶塞具有特殊性能的主要成分。

然而,在硫化剂的制备过程中,可能会产生一些有害物质,如亚硫酸盐、二硫化碳等。

因此,对丁基胶塞化学助剂的检测就显得尤为重要。

为了检测丁基胶塞化学助剂的质量,目前常用的方法包括化学分析、物理测试、显微分析等。

其中,物理测试可以通过对丁基胶塞的物理性质进行分析来检测化学助剂的质量。

例如,可以对硫化剂的含量、密度、熟化时间等进行测试,以确定丁基胶塞的质量是否合格。

同时,为了确保丁基胶塞与药物的相容性,目前也有许多研究对此进行了探讨。

例如,研究表明,某些药物会影响丁基胶塞的物理性质,如硫化剂的含量、成分等。

因此,在使用丁基胶塞作为药物包装材料时,需要考虑药物对丁基胶塞的影响。

总之,丁基胶塞的化学助剂的检测和与药物的相容性研究非常重要,对于保障药物的质量和安全性至关重要。

未来,需要进一步加强对丁基胶塞的研究,促进丁基胶塞在药物包装材料中的安全应用。

欧盟与中国检测方法对比

欧盟与中国检测方法对比

铵离子
精密量取试验液10ml,加碱性碘化汞钾2ml, 放置15分钟,如显色,与氯化铵溶液(取氯 颜色不得比对照液更深 化铵31.5mg加无氨水适量溶解并稀释至 (0.0002%) 1000.0ml)2.0ml,加空白提取液8ml与碱性 碘化汞钾试液制成的对照液比较。
锌离子
——
——
锌离子
取供试品液,用孔径0.45um的滤膜过滤,精 密量取10ml,加2mol/L盐酸1ml和亚铁氰化 钾试液(称取4.2g亚铁氰化钾三水化合物, 用溶解并稀释至100ml,摇匀,即得)3滴混 供试品液不显色或颜色 合,不得显色;如显色,与标准锌溶液(临 不得比对照液更深 用前,称取44.0mg硫酸锌七水化合物,用新 煮沸并冷却的水溶解并稀释至1000.0ml) 3.0ml,加空白对照液8ml与2mol/L盐酸1ml 和亚铁氰化钾试液3滴对照液比较。 在供试品液制备5小时内进行下述试验:用 电导仪测定,用水冲洗测定电极(光亮铂电 极或铂黑电极)数次,取空白对照液冲洗电 极至少2次,测定空白对照液的电导率。。 再用供试品液冲洗电极至少2次,测定供试 品液的电导率。测定温度为20℃±1℃,如 果测定温度不在此条件下,则应对温度进行 校正。
不挥发物
不得过4.0mg
重金属
同空白溶液比较, 如果对照溶液不呈 浅棕色,则测试无 效。供试液的颜色 不得比对照液更深
重金属
精密量取试验液10ml,加醋酸盐缓冲液 (pH3.5)2ml,照重金属检查法(中华人民 含重金属不得过百万分 之一 共和国药典2000版二部附录Ⅷ H第一法测定 。)

在装有14ml纯化水的试管内溶解规定的 所测物质。有必要的话,在纯化水中溶 解氢氧化钠R并定容至15ml。在已配溶液 中滴加0.3ml四碘汞酸钾溶液。将10ml标 测试液颜色不得比 准钠溶液(1ppmNH4)、5ml水和0.3ml四 标准样品颜色更深 碘汞酸钾溶液混合,制得标准溶液,之 后将试管上塞。5分钟,比较测试液和标 准样品颜色。

国产药用丁基胶塞中微量成分分析

国产药用丁基胶塞中微量成分分析

国产药用丁基胶塞中微量成分分析的报告,800字
本报告旨在对国产药用丁基胶塞中的微量成分进行分析。

所研究的样品为国产丁基胶塞。

该样品以常温和常压
(101.3kPa)下进行研究。

样品分析方法:为了评估微量成分含量,我们采用等温液相色谱-串联质谱(LC-MS/MS)分析技术。

利用LC-MS/MS技术,样品溶液通过后续的化学反应容器由高压泵驱动,经过超滤膜渗透到液相色谱分离设备中,再被分离,分离出的物质通过质谱仪,以蓝宝石数码技术的形式,对物质进行测定分析。

分析结果:本次样品分析结果显示,国产药用丁基胶塞中,含有氯化钙、丁二酸、乙酸乙酯、聚乙二醇,次氯酸钠、磷酸氢钠以及烷基硫醇等共7种微量成分。

总体分析:7种微量成分,占样品总重量的比例分别为0.07%、0.13%、1.2%、2.9%、4.4%、4.16%和17.4%,其中氯化钙、
丁二酸、乙酸乙酯、聚乙二醇和烷基硫醇的比例较小,次氯酸钠和磷酸氢钠的比例较大。

结论:本次实验结果表明,国产药用丁基胶塞中,含有7种
微量成分,其中次氯酸钠和磷酸氢钠的比例较大,而氯化钙、丁二酸、乙酸乙酯、聚乙二醇和烷基硫醇的比例较小。

根据
上述结果,可以认为国产药用丁基胶塞中微量成分质量合格可用,能够满足相关药品生产要求。

药用丁基胶塞化学助剂检测及与药物相容性研究进展

药用丁基胶塞化学助剂检测及与药物相容性研究进展

药用丁基胶塞化学助剂检测及与药物相容性研究进展刘莉;李婷婷;童伟;朱碧君【摘要】包装材料对保证药品的稳定性起着至关重要的作用,与人们的用药安全直接相关.由于药用丁基胶塞成分的复杂性,给这方面的研究带来很大的困难.药用丁基胶塞胶塞与药物的相容性研究,在国内也几乎是一个空白,胶塞对药物性质、产品质量造成影响的原因、机理至今未有确切的结论.本文综述药用丁基胶塞有效成分的检测及与药物相容性研究.【期刊名称】《江西化工》【年(卷),期】2017(000)001【总页数】4页(P11-14)【关键词】药用丁基胶塞;相容性研究【作者】刘莉;李婷婷;童伟;朱碧君【作者单位】成都市食品药品检验研究院,四川成都 610045;成都市食品药品检验研究院,四川成都 610045;江西省肿瘤医院药剂科,江西南昌 330029;江西省药品检验检测研究院、江西省药品与医疗器械质量工程技术研究中心,江西南昌330029【正文语种】中文丁基橡胶塞是医药包装材料的升级换代产品,主要用于替代传统天然橡胶瓶塞。

丁基橡胶瓶塞是一种有诸多优越性能的医药包装材料,比天然橡胶瓶塞具有更好的使用性,其气体透过率约为天然橡胶的1/20,丁基橡胶的耐热性、耐候性和耐臭氧氧化性都很突出,最高使用温度可达200℃,可以长时间暴露于阳光和空气中而不易损坏。

药用丁基橡胶是由异丁烯和少量异戊二烯(<3%)在超低温(-95℃)条件下聚合而成的合成橡胶,其特有的化学稳定性、优良的密封性保证了药品质量,提高了用药安全性,还减少了天然胶塞生产所需的烫蜡工序、垫加绦纶膜等工序。

丁基胶塞在产品标准、生产水平、使用性能、产品质量等方面大大优于天然胶塞。

常用的有氯化丁基橡胶和溴化丁基橡胶两类,分别为CIIR和BIIR。

卤化丁基橡胶中,氯化丁基橡胶中结合氯含量为1.1%~1.3%(质量分数);溴化丁基橡胶中结合溴含量为1.9%~2.1%。

卤化丁基胶塞具有吸湿率低、化学稳定性好、气密性好、无生理毒副作用等显著特点[1]。

药用丁基胶塞质量标准模板

药用丁基胶塞质量标准模板

药用丁基胶塞质量标准药用氯化丁基橡胶塞标准( 试行) YBB 0004 本标准适用于直接与注射剂接触的氯化丁基橡胶塞。

【外观】取本品数个, 目视检测, 表面色泽应均匀, 不得有污点、杂质、气泡、裂纹、缺胶、粗糙、胶丝、胶屑、海绵状、毛边; 不得有除边造成的残缺或锯齿现象; 不得有模具造成的明显痕迹。

【鉴别】( 1) 称取本品5~20g, 置于干燥的试管中, 将长约4毫米的钠片一片置于固定并倾斜的试管中, 使其恰好位于试样之上, 用火焰的尖端加热试管, 将钠融化在试样上, 继续加热2分钟, 使呈深红色, 冷却后加入乙醇, 将过剩的钠醇化, 加水约10ml溶解, 过滤, 滤液备用。

A: 取滤液1.5ml置于试管中, 加硝酸酸化, 煮沸1~2分钟, 加入硝酸银1滴, 应产生白色沉淀。

B: 取滤液0.2ml, 置于微量试管中, 加氯仿1滴, 加稀硫酸1滴, 加薪配置的氨水1滴( 或3%H2O2溶液2~3滴) , 经振荡混匀后, 静止5分钟, 氯仿层应不显色。

( 2) 红外光谱取本品约3g切成3mm×3mm小块置索氏抽提器中用丙酮或适宜的溶剂回流浸提8小时, 取残渣80℃烘干, 取0.1~0.2g置于裂解管的底部, 然后用试管夹水平的将裂解管移到酒精灯上加热, 当出现裂解产物冷凝在裂解管冷端时, 再继续加热至裂解基本完全但没碳化为止, 取少许裂解物滴在溴化钾片上, 在80℃烘干, 照分光光度法( 《中华人民共和国药典》二部ⅣC) 测定, 应与对照图谱基本一致。

【穿刺落屑】输液瓶用胶塞: 取10只被测胶塞和10只已知穿落屑数的胶塞分别装在与其相配的输液瓶上, 每只瓶中注入半瓶水。

加上铝盖,用手动封盖机封口,打开铝盖穿刺部位。

按先被测胶塞再已知穿刺落屑数胶塞的顺序交替穿刺胶塞。

穿刺时,胶塞保持直立,握持金属穿刺器( 见图1) 垂直向胶塞标记区域内穿刺, 晃动数秒后拨出穿刺器。

每次穿刺前用丙酮或甲基—异丁基酮擦拭穿刺器。

药用丁基胶塞的材质-概述说明以及解释

药用丁基胶塞的材质-概述说明以及解释

药用丁基胶塞的材质-概述说明以及解释1.引言1.1 概述药用丁基胶塞是一种常见的医疗器械材料,广泛应用于药品容器的密封和注射器的橡胶塞。

它由丁基橡胶制成,具有良好的柔软性、耐腐蚀性和密封性能。

药用丁基胶塞的主要作用是防止药物在储存和输送过程中的泄漏和污染,确保药品的质量和安全性。

在医药领域中,药用丁基胶塞被广泛用于药瓶、针筒和注射器等容器的密封。

丁基胶塞的材质选择非常重要,它直接影响着药品的稳定性、保存期限和使用效果。

因此,在选择药用丁基胶塞材质时需要考虑多方面因素。

首先,药用丁基胶塞的材质应具有优异的化学稳定性和生物相容性。

医药产品经常与各种药物接触,因此胶塞的材质在接触药物后不应引起有害物质的释放或产生任何不良反应。

此外,药用丁基胶塞应具有良好的耐腐蚀性,能够抵抗药品中的溶剂、溶剂和氧化剂等物质的侵蚀,以确保药品的纯度和效力。

其次,药用丁基胶塞的材质还应具有较好的机械性能。

胶塞的弹性和稳定性是确保其与容器紧密密封的重要特性,不仅要能够顺利穿透瓶口或针头,还要能够防止气体或液体的泄漏。

此外,在长时间使用或高压情况下,胶塞应能够保持一定的形状和稳定性,以确保药品的安全和有效性。

最后,为了满足不同的医药应用需求,药用丁基胶塞的材质还应具有可扩展性。

不同药品对胶塞材质的要求不同,因此需要根据具体的药品性质和应用环境,选择材质的硬度、耐高温性、阻氧性等特性。

这样可以更好地适应各种药品的保存和使用要求,提高药品的质量和稳定性。

综上所述,药用丁基胶塞的材质选择是确保药品质量和安全性的重要环节。

在选择材料时需要考虑化学稳定性、生物相容性、耐腐蚀性、机械性能和可扩展性等因素,以满足不同药品的需求。

随着科学技术的不断进步,我们可以期待药用丁基胶塞材质在未来的发展中更加先进和多样化,为医药行业带来更多的便利和创新。

1.2 文章结构文章结构部分的内容可以包括以下几个方面:(1)本文主要分为引言、正文和结论三个部分,以系统地介绍药用丁基胶塞的材质选择要点以及展望其未来的发展方向。

【免费下载】 药用丁基胶塞质量标准

【免费下载】 药用丁基胶塞质量标准

药用丁基胶塞质量标准药用氯化丁基橡胶塞 标准(试行) YBB 00042002本标准适用于直接与注射剂接触的氯化丁基橡胶塞。

【外观】取本品数个,目视检测,表面色泽应均匀,不得有污点、杂质、气泡、裂纹、缺胶、粗糙、胶丝、胶屑、海绵状、毛边;不得有除边造成的残缺或锯齿现象;不得有模具造成的明显痕迹。

【鉴别】(1)称取本品5~20g ,置于干燥的试管中,将长约4毫米的钠片一片置于固定并倾斜的试管中,使其恰好位于试样之上,用火焰的尖端加热试管,将钠融化在试样上,继续加热2分钟,使呈深红色,冷却后加入乙醇,将过剩的钠醇化,加水约10ml 溶解,过滤,滤液备用。

A :取滤液1.5ml 置于试管中,加硝酸酸化,煮沸1~2分钟,加入硝酸银1滴,应产生白色沉淀。

B :取滤液0.2ml ,置于微量试管中,加氯仿1滴,加稀硫酸1滴,加薪配置的氨水1滴(或3%H2O2溶液2~3滴),经振荡混匀后,静止5分钟,氯仿层应不显色。

(2)红外光谱取本品约3g 切成3mm×3mm 小块置索氏抽提器中用丙酮或适宜的溶剂回流浸提8小时,取残渣80℃烘干,取0.1~0.2g 置于裂解管的底部,然后用试管夹水平的将裂解管移到酒精灯上加热,当出现裂解产物冷凝在裂解管冷端时,再继续加热至裂解基本完全但没碳化为止,取少许裂解物滴在溴化钾片上,在80℃烘干,照分光光度法(《中华人民共和国药典》2000年版二部ⅣC )测定,应与对照图谱基本一致。

【穿刺落屑】输液瓶用胶塞:取10只被测胶塞和10只已知穿落屑数的胶塞分别装在与其相配的输液瓶上,每只瓶中注入半瓶水。

加上铝盖,用手动封盖机封口,打开铝盖穿刺部位。

按先被测胶塞再已知穿刺落屑数胶塞的顺序交替穿刺胶塞。

穿刺时,胶塞保持直立,握持金属穿刺器(见图1)垂直向胶塞标记区域内穿刺,晃动数秒后拨出穿刺器。

每次穿刺前用丙酮或甲基—异丁基酮擦拭穿刺器。

穿刺器不得有损坏,并保持锋利(如穿器损坏,须换用新的)。

丁基橡胶药用瓶塞检验规程

丁基橡胶药用瓶塞检验规程

编号:ZL-SOP-QC-001-00目的:建立丁基橡胶药用瓶塞检验操作规程范围:本规程适用于丁基橡胶药用瓶塞的检验责任人:质检科内容:1.器具:量筒、烧杯、刻度吸管、pH计、移液管、100ml容量瓶、TU-1800型紫外分光光度计、微孔滤膜、10ml移液管、电炉、天平、锥形瓶、电热恒温干燥箱、瓷蒸发皿、干燥器、纳氏比色管、高温电炉。

2.试剂:淀粉指示液、高锰酸钾液(0.002mol/L)、硫代硫酸钠滴定液(0.01mol/L)、醋酸盐缓冲液(pH3.5)、碱性碘化汞钾、氯化铵溶液、2mol/L 盐酸、亚铁氰化钾试液、标准锌溶液、标准铅溶液(1ml相当于10μg的Pb)、硫代乙酰胺试液、混合液、碘化钾、稀硫酸、0.1%氯化钾溶液。

3.检查:3.1外观:3.1.1操作步骤:取样品100个,目视检测。

3.1.2结果判定:表面色泽应均匀,不得有污点、杂质、气泡、裂纹、缺胶、粗糙、胶丝、海绵状毛边;不得有除边造成的残缺或锯齿现象;不得有模具造成的明显痕迹,判为合格。

3.2灰分:3.2.1操作步骤:3.2.1.1分别称取样品1.0g两份,放入已炽灼至恒重的两个坩埚中,精密称定;3.2.1.2放入高温电炉中,缓缓炽灼至完全炭化;3.2.1.3再放入800℃炽灼至完全灰化,移置干燥器内;3.2.1.4放冷至室温,精密称定后,再在800℃炽灼至恒重。

4.2.2结果判定:遗留残渣不得过45%,判为合格。

3.3澄清度与颜色:3.3.1操作步骤:取供试液10.0ml置纳氏比色管中。

4.3.2结果判定:溶液应澄清无色。

如显浑浊,与2号浊度标准液比较,不得更浓;如显色,与黄绿色5号标准比色液比较,不得更浓,判为合格。

3.3.3注:试验液S1和空白液S0的制备按《丁基橡胶药用瓶塞质量标准》进行。

3.4酸碱度3.4.1操作步骤3.4.1.1用量筒分别量取试验液S1和空白液S0各20ml,置两个小烧杯中。

3.4.1.2向两个小烧杯中各加入氯化钾溶液(1→1000)1.0ml。

药包材标准中丁基胶塞质量要求及测试方法介绍

药包材标准中丁基胶塞质量要求及测试方法介绍

药包材标准中丁基胶塞质量要求及测试方法介绍药包材标准中丁基胶塞质量要求及测试方法介绍丁基橡胶塞在洁净度、化学稳定性、气密性等方面的性能都非常好,所以广泛应用于输液、口服液等药品包装中。

由于丁基胶塞在药品行业应用广泛,而且胶塞产品直接接触药品,所以国家出台了很多相关标准来控制丁基胶塞的产品质量。

以下我们结合国家药包材标准的要求来介绍丁基胶塞产品的性能要求和测试方法。

一、参考标准(部分):YBB00042005-2015注射液用卤化丁基橡胶塞YBB00052005-2015注射用无菌粉末用卤化丁基橡胶塞YBB00322004-2015注射剂用胶塞垫片穿刺力测定法YBB00332004-2015注射用胶塞垫片穿刺落屑测定法1.穿刺落屑取样品10个,照注射剂用胶塞、垫片穿刺落屑测定法YBB00332004-2015测定,落屑数应不得过20粒。

测定法:选择20个注射剂瓶,每个瓶内加1/2公称容量的水。

取10个被测胶塞和10个已知穿刺落屑胶塞分别装在注射剂瓶上,盖上铝盖或铝塑组合盖,封口后进行预处理。

预处理完成后用丙酮或其他适当的有机溶剂擦拭金属穿刺器,然后手持穿刺器,垂直穿刺被测试胶塞上的标记部位,刺入后晃动注射剂瓶数秒后拔出穿刺器。

将注射剂瓶中水全部通过一张滤纸过滤,在人眼距离滤纸20cm 的位置,用肉眼观察滤纸上的落屑数,必要时可以通过显微镜进一步证实落屑大小和数量。

附金属穿刺器标准要求1.穿刺力取样品10个。

照注射剂用胶塞、垫片穿刺力测定法YBB00322004-2015第二法测定,穿刺瓶塞所需的力均不得超过10N。

测定法:依据标准要求对胶塞样品进行预处理。

取10个胶塞配套的注射剂瓶,分别加入公称容量的水,装上预处理过的被测胶塞,加上铝盖或者铝塑组合盖,封口。

将一只注射针置于材料试验机上固定,将注射剂瓶放入材料试验机,打开铝盖或铝塑组合盖,漏出胶塞标记部位,穿刺器以200mm/min的速度进行垂直穿刺,记录胶塞穿刺所施加的最大力值。

抗生素药物包装中丁基胶塞使用的有关问题

抗生素药物包装中丁基胶塞使用的有关问题

发布日期20090107栏目化药药物评价>>综合评价标题抗生素药物包装中丁基胶塞使用的有关问题作者蒋煜部门审评三部正文内容国家局于2008年12月下发了“关于进一步加强使用丁基胶塞的头孢类注射剂监督管理的通知”,详文可见国家局网站国食药监办[2008]765号文。

通知说明,为解决头孢类注射剂澄清度问题,保证产品质量,保障公众用药安全,通知了加强使用丁基胶塞生产头孢类注射剂的监督管理。

并要求对于注射用头孢曲松钠,在选择丁基胶塞生产药品时进行相容性实验,对购入的每批丁基胶塞和生产的每批药品出厂前,依此方法进行检验,合格后方可出厂。

对于其他头孢类注射剂,药品生产企业可参考该方法,自行建立适宜的快速验证方法。

文件附件提供了注射用头孢曲松钠与丁基胶塞相容性加速实验方法:取注射用头孢曲松钠,于60℃恒温箱内,倒置放置5天,取出后测定样品溶液的澄清度,应小于1#浊度标准液。

丁基胶塞是目前国内抗生素玻璃瓶的主要包装材料之一,也是β-内酰胺类抗生素常采用的一种包装材料。

国家药品监督管理局曾要求于2001年7月1日起中止在头孢拉啶、头孢哌酮钠、头孢三嗪钠(头孢曲松钠)、头孢唑啉钠,羧苄青霉素钠、硫酸丁胺卡那霉素、硫酸卡那霉素等十三种抗生素中停止销售和使用普通天然胶塞,并陆续在其他药物中也停止其使用,取而代之以丁基胶塞。

目前,药用卤化丁基胶塞类产品主要可分为氯化丁基橡胶塞,溴化丁基橡胶塞。

另外,国家局于2006年下发的(国产)直接接触药品的包装材料和容器生产审批中要求,包装材料申报企业应选择有代表性的试验药品,提供采用申报产品包装的药品同时进行的稳定性试验(药物相容性试验)研究资料。

文献显示,不同包装材料企业生产的丁基胶塞质量存在一定差异,对产品澄清度有不同程度的影响。

丁基胶塞在制造过程中要经过硫化、硅化、卤化,以及后处理等步骤。

在此过程中加入的某些填充剂、增塑剂等,以及丁基胶塞采用的不同清洗工艺后,都可能影响丁基胶塞与药物的相容性,从而影响药品的澄清度。

丁基胶塞的检测SOP

丁基胶塞的检测SOP

1.目的规范丁基胶塞的检测程序2.适用范围丁基胶塞的检测3.职责3.1. 质量管理部:负责本规程的起草、修订、审核、培训、实施和监督。

3.2. 质量管理部QC人员:负责本规程的实施。

3.3. 总经理:负责本规程的批准。

4.定义无5.引用标准《药品生产质量管理规范》2010年版6.材料6.1.仪器设备无6.2.器材、用具无6.3.其他无7.流程图无8.内容8.1.外观:取待检品数个,观察针刺圈内或与内容物接触面有无污点为、杂质、针刺圈内或密封面有无气泡、裂纹。

8.2. 穿刺落屑:选择与胶塞配套的500ml(口径26mm或28mm )20个,瓶内加1/2公称容量水,取待检品10个,已知穿刺落屑数的胶塞10个,分别装到瓶上,盖上铝塑组合盖,用手动封口机封口,放入高压蒸汽消毒器中,在121℃±2℃下保持30分钟,取出冷却至室温,分两排放置,第一排为被测胶塞,第二排为已知胶塞。

用丙酮或其它适当的有机溶剂擦拭金属穿刺针,然后将其浸在蒸馏水中。

手持穿刺针,垂直穿刺第一排第一个被刺胶塞上的标记部位,剌入后,晃动玻璃瓶数秒后,拔出穿刺针。

按上述步骤穿刺第二排第一个已知穿刺落屑数胶塞。

以此类推,按先被胶塞再已知穿刺落屑数胶塞的顺序,交替垂直穿刺胶塞上的标记部位,直至所有胶塞被穿刺一次。

将第一排瓶中水全部通过一张滤纸过滤,确保瓶中不残留落屑,在人眼距离滤纸25厘米的位置,用肉眼观察滤纸上的落屑数(相当于50μm以上的颗粒),必要时可通过显微镜进一步证实落屑大小和数量。

对已知穿刺落屑数的胶塞同法计数。

结果显示:分别记录两排瓶子的可见落屑数(即每十针的落屑总数)。

若已知穿刺落屑胶塞的结果与先已知的结果具有一致性,则应判被测胶塞测得结果有效。

反之,则无效。

在穿刺过程中,若有两个以上(含两个)胶塞在穿刺过程中被推入瓶中,则判该项不合格,若10个被测胶塞中有一个被推入瓶中,则另取10个胶塞重新试验,不得有胶塞被推入瓶中。

我国药用丁基胶塞的应用现状和存在的问题

我国药用丁基胶塞的应用现状和存在的问题

我国药用丁基胶塞的应用现状和存在的问题
纪立伟;胡欣
【期刊名称】《中国药业》
【年(卷),期】2003(012)012
【摘要】@@ 药品包装中使用的胶塞有丁基橡胶瓶塞(以下简称丁基胶塞)和天然橡胶瓶塞(以下简称天然胶塞)两种.在我国的制药史上,长期采用的是加垫涤纶膜的翻口天然胶塞.
【总页数】2页(P25-26)
【作者】纪立伟;胡欣
【作者单位】卫生部北京医院药剂科,北京,100730;卫生部北京医院药剂科,北京,100730
【正文语种】中文
【中图分类】TQ460.4
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Summary1、Penetrability[YBB]Take 10 rubber closures, test according to the second method of YBB60072012, the average puncture force does not exceed 10N.[EP] Fill 10 suitable vials to the nominal volume with water R, fit the closures to be examined and secure with a cap. Using for each closure a new, lubricated long-bevel(1) (bevel angle 12 ± 2°) hypodermic needle with an external diameter of 0.8 mm, pierce the closures with the needle perpendicular to the surface. The force required for piercing, determined with an accuracy of ± 0.25 N (25 gf), is not greater than 10 N (1 kgf) for each closure.[JP]None[USP]Fill 10 suitable vials to the nominal volume with water, fit the closures to be examined, and secure with a cap. Using a new hypodermic needle as described above for each closure, pierce the closure with the needle perpendicular to the surface.Requirement—The force for piercing is no greater than 10 N (1 kgf) for each closure, determined with an accuracy of ± 0.25 N (25 gf).2、Fragmentation[YBB]Take 10 rubber closures, test according to the second method of YBB60082012, The total number of fragments does not exceed 5.[EP] For closures intended to be pierced by a hypodermic needle, carry out the following test. If the closures are to be used for aqueous preparations, place in12 clean vials a volume of water R corresponding to the nominal volume minus4 ml, close the vials with the closures to be examined, secure with a cap andallow to stand for 16 h. If the closures are to be used with dry preparations, close 12 clean vials with the closures to be examined. Using a lubricated long-bevel(1) (bevel angle 12 ±2°) hypodermic needle with an external diameter of 0.8 mm fitted to a clean syringe, inject into the vial 1 ml of water R and remove 1 ml of air ; carry out this operation 4 times for each closure, piercing each time at a different site. Use a new needle for each closure and check that the needle is not blunted during the test. Pass the liquid in the vials through a filter having approxi mately 0.5 μm pores. Count the fragments of rubber visible to the naked eye. The total number of fragments does not exceed5. This limit is based on the assumption that fragments with a diameter equal toor greater than 50 μm are visible to the naked eye; in cases of doubt or dispute, the fragments are examined with a microscope to verify their nature and size. [JP] None[USP] Closures for Liquid Preparations— Fill 12 clean vials with water to 4 mL less than the nominal capacity. Fit the closures to be examined, secure with acap, and allow to stand for 16 hours.Closures for Dry Preparations— Fit closures to be examined into 12 cleanvials, and secure each with a cap.Procedure— Using a hypodermic needle as described above fitted to a cleansyringe, inject into each vial 1 mL of water while removing 1 mL of air. Repeat this procedure 4 times for each closure, piercing each time at a different site.Use a new needle for each closure, checking that it is not blunted during the test.Filter the toatal volume of liquid in all the vials through a single filter with a nominal pore size no greater than 0.5 µm. Count the rubber fragments on the surface of the filter visible to the naked eye.Requirement— There are no more than 5 fragments visible. This limit is based on the assumption that fragments with a diameter >50 µm are visible to the naked eye. In case of doubt or dispute, the particles are examined microscopically to verify their nature and size.3、Sealing test of rubber closure and container[YBB] Take 10 rubber closures into the beaker, boil for 5 min , take out and dry 1h at 70℃ and ready to use. Fill 10 suitable vials to the nominal volume with water, fit the closures to be examined and secure with a cap. Heat in an autoclave so that a temperature of 121 ± 2 °C and maintain at this temperature for 30 min.Cool to room temperature and then place 24h, Immerse the vials upside down ina 10% solution of methylene blue R and reduce the external pressure by 25 kPafor 30 min. Restore atmospheric pressure and leave the vials immersed for 30 min. Rinse the outside of the vials. None of the vials contains any trace of colored solution.[EP]None[JP]None[USP] None4、Self-Sealing Capacity[YBB]Take the samples from sealing test of rubber closure and container, using for a hypodermic needle (YBB60082012 method 2), pierce each closure 3 times, change the hypodermic needle after it is used 10 times ,piercing each time at a different site.The vials upside down in a 10% solution of methylene blue R and reduce the external pressure by 25 kPa for 30 min. Restore atmospheric pressure and leave the vials immersed for 30 min. Rinse the outside of the vials. None of the vials contains any trace of colored solution.[EP]For closures intended to be used with multidose containers, carry out the following test. Fill 10 suitable vials to the nominal volume with water R, fit the closures to be examined and secure with a cap. Using for each closure a new hypodermic needle with an external diameter of 0.8 mm, pierce each closure 10 times, piercing each time at a different site. Immerse the vials upright in a 1 g/l solution of methylene blue R and reduce the external pressure by 27 kPa for 10 min. Restore atmospheric pressure and leave the vials immersed for 30 min.Rinse the outside of the vials. None of the vials contains any trace of coloured solution.[JP]None[USP]Procedure—Fill 10 suitable vials with water to the nominal volume. Fit the closures that are to be examined, and cap. Using a new hypodermic needle as described above for each closure, pierce each closure 10 times, piercing each time at a different site. Immerse the 10 vials in a solution of 0.1% (1 g per L) methylene blue, and reduce the external pressure by 27 kPa for 10 minutes.Restore to atmospheric pressure, and leave the vials immersed for 30 minutes.Rinse the outside of the vials.Requirement—None of the vials contain any trace of blue solution.5、Total Ash[YBB] Take the rubber closures, test according to YBB600212012, should be comply with the standard.[EP]The total ash (2.4.16) is within ± 10 per cent of the result obtained with the type sample.[JP]None[USP] None6、Volatile Sulfides[YBB]Take the rubber closures, according to the YBB60052012, should be comply with the standard.[EP] Place closures, cut if necessary, with a total surface area of 20 ± 2 cm2 in a 100 ml conical flask and add 50 ml of a 20 g/l solution of citric acid R. Place a piece of lead acetate paper R over the mouth of the flask and maintain the paper in position by placing over it an inverted weighing bottle. Heat in an autoclave at 121 ± 2℃ for 30 min. Any black stain on the paper is not more intense than that of a standard prepared at the same time in the same manner using 0.154 mg of sodium sulphide R and 50 ml of a 20 g/l solution of citric acid R.[JP]None[USP] Procedure— Place closures, cut if necessary, with a total surface area of 20 ± 2 cm2 in a 100-mL flask, and add 50 mL of a 20 g per L citric acid solution. In the same manner and at the same time, prepare a control solution in a separate 100-mL flask by dissolving 0.154 mg of sodium sulfide in 50 mL of a 20 g per L citric acid solution. Place a piece of lead acetate paper over the mouth of each flask, and hold the paper in position by placing over it an inverted weighing bottle. Heat the flasks in an autoclave at 121 ± 2℃for 30minutes.Requirement—Any black stain on the paper produced by Solution S is not more intense than that produced by the control solution.7、Preparation of Solution S[YBB] Put a number of uncut closures corresponding to a surface area of about 200 cm2 in a suitable glass container, cover with purified water( sample: water=1:2), boil for 5 min and rinse 5 times with the same volume of purified water. Place the washed closures in a conical flask, add the same volume of water and weigh.Cover the mouth of the flask with a borosilicate-glass beaker. Heat in an autoclave so that a temperature of 121 ± 2 °C is reached within 20 min to 30 min and maintain at this temperature for 30 min. Cool to room temperature.Make up to the original mass with purified water. Shake and immediately separate the solution from the rubber by decantation. Shake solution S before each test Blank. Prepare a blank in the same manner using 400 mL of water for purified water.[EP] Solution S.Introduce a number of uncut closures corresponding to a surface area of about 100 cm2in a suitable glass container, cover with water for injections R, boil for 5 min and rinse 5 times with cold water for injections R.Place the washed closures in a wide-necked flask (glass type I, 3.2.1), add 200 ml of water for injections R and weigh. Cover the mouth of the flask with a borosilicate-glass beaker. Heat in an autoclave so that a temperature of 121 ±2 °C is reached within 20 min to 30 min and maintain at this temperature for 30min. Cool to room temperature over about 30 min. Make up to the original mass with water for injections R. Shake and immediately separate the solution from the rubber by decantation. Shake solution S before each testBlank. Prepare a blank in the same manner using 200 ml of water for injections R.[JP] Wash the rubber closures with water, and dry at room temperature. Place them in a glass container, add water exactly 10 times the mass of the test material, close with a suitable stopper, heat at 121℃ for 1 hour in an autoclave, take out the glass container, allow to cool to room temperature,then take out immediately the rubber closures, and use the remaining solution as the testsolution. Prepare the blank solution with water in the same manner. Perform the following tests with the test solution and the blank solution[USP] Place whole, uncut closures corresponding to a surface area of 100 ± 10 cm2 intoa suitable glass container. Cover the closures with 200 mL of Purified Water orWater for Injection. If it is not possible to achieve the prescribed closure surface area (100 ± 10 cm2) using uncut closures, select the number of closures that will most closely approximate 100 cm2, and adjust the volume of water used to the equivalent of 2 mL per each 1 cm2 of actual closure surface area used. Boil for 5 minutes, and rinse five times with cold Purified Water or Water for InjectionPlace the washed closures into a Type I glass wide-necked flask (see Containers—Glass 660 ), add the same quantity of Purified Water or Water for Injection initially added to the closures, and weigh. Cover the mouth of the flask with a Type I glass beaker. Heat in an autoclave so that a temperature of 121 ± 2℃ is reached within 20 to 30 minutes, and maintain this temperature for30 minutes. Cool to room temperature over a period of about 30 minutes. AddPurified Water or Water for Injection to bring it up to the original mass. Shake, and immediately decant and collect the solution. [NOTE—This solution must be shaken before being used in each of the tests]Prepare a blank solution similarly, using 200 mL of Purified Water or Water for Injection omitting the closures8、Appearance of solution[YBB]According to the part 2 of Chinese pharmacopoeia, 2010 edition of appendixⅨB and appendix IX A, standard solution is not more opalescent than reference suspension II. Standard solution is not more intensely coloured than No.5 reference solution[EP] Solution S is not more opalescent than reference suspension II for type I closures and is not more opalescent than reference suspension III for type II closures(2.2.1). Solution S is not more intensely coloured than reference solution GY5(2.2.2, Method II).[JP] Place 5 mL of the test solution in a glass-stoppered test tube of about 15 mm in inner diameter and about 200 mm in length, and shake vigorously for 3 minutes.The foam arisen disappears almost completely within 3 minutes.[USP] Determination of Turbidity (Opalescence)Procedure A: Visual Comparison— Use identical test tubes made of colorless, transparent, neutral glass with a flat base and an internal diameter of 15 to 25 mm. Fill one tube to a depth of 40 mm with Solution S, one tube to the same depth with water, and four others to the same depth with Reference Suspensions A, B, C,and D. Compare the solutions in diffuse daylight 5 minutes after preparation of the Reference Suspensions, viewing vertically against a black background. The light conditions shall be such that Reference Suspension A can be readily distinguished from water and that Reference Suspension B can be readily distinguished fromReference Suspension A.REQUIREMENT—Solution S is not more opalescent than Reference Suspension B for Type I closures, and not more opalescent than Reference Suspension C for Type II closures. Solution S is considered clear if its clarity is the same as that of water when examined as described above, or if its opalescence is not more pronounced than that of Reference Suspension A (refer to Table 3).Procedure B: Instrumental Comparison—Measure the turbidity of theReference Suspensions in a suitable calibrated turbidimeter (see Spectrophotometry and Light Scattering 851 ). The blank should be run and the results corrected for the blank. Reference Suspensions A, B, C, and D represent 3, 6, 18 and 30 Nephelometric Turbidity Units (NTU), respectively. Measure the turbidity of Solution S using the calibrated turbidimeter. REQUIREMENT—The turbidity of Solution S is not greater than that for Reference Suspension B (6 NTU FTU) for Type I closures, and is not greater than that forReference Suspension C (18 NTU FTU) for Type II closures (refer to Table 3).Determination of ColorColor Standard— Prepare a solution by diluting 3.0 mL of Matching Fluid O (see Color and Achromicity 631 ) with 97.0 mL of diluted hydrochloric acid. Procedure—Use identical tubes made of colorless, transparent, neutral glass with a flat base and an internal diameter of 15 to 25 mm. Fill one tube to a depth of 40 mm with Solution S, and the second with Color Standard. Compare the liquids in diffuse daylight, viewing vertically against a white background. Requirement—Solution S is not more intensely colored than the Color Standard.9、Acidity or Alkalinity(PH)[YBB]Take each of 20 ml blank solution and solution S, respectively with KCl solution1 ml, According to the part2 of Chinese pharmacopoeia, 2010 edition ofappendixⅥH, the difference between the two may not be over 1.0.[EP] To 20ml of solution S add 0.1ml of bromothymol blue solution R1. Not more than 0.3ml of 0.01 M sodium hydroxide or 0.8 ml of 0.01 M hydrochloric acid is required to obtain either a blue or a yellow colour, respectively.[JP] To 20 mL each of the test solution and the blank solution add 1.0 mL each of potassium chloride solution, prepared by dissolving 1.0 g of potassium chloride in water to make 1000 mL. The difference of pH between the two solutions is not more than 1.0[USP] Bromothymol Blue Solution—Dissolve 50 mg of bromothymol blue in a mixture of 4 mL of 0.02 M sodium hydroxide and 20 mL of alcohol. Dilute with water to 100 mL.Procedure— To 20 ml of Solution S add 0.1 ml of Bromothymol Blue Solution.If the solution is yellow, titrate with 0.01 N sodium hydroxide until a blue endpoint is reached. If the solution is blue, titrate with 0.01 N hydrochloric acid until a yellow endpoint is reached. If the solution is green, it is neutral and no titration is required.Blank Correction—Test 20 mL of Blank similarly. Correct the results obtained for Solution S by subtracting or adding the volume of titrant required for the Blank, as appropriate. (Reference Titrimetry 541 .)Requirement— Not more than 0.3 ml of 0.01 N sodium hydroxide produces a blue color, or not more than 0.8 ml of 0.01 N hydrochloric acid produces a yellow color, or no titration is required.10、Absorbance[YBB] Filter solution S on a membrane filter having approximately 0.45 μm pores.Measure the absorbance of the filtrate at wavelengths from 220 nm to 360 nm using the blank as compensation liquid. At these wavelengths, the absorbance does not exceed 0.1(according to the part 2 of Chinese pharmacopoeia, 2010 edition of appendixⅣA).[EP] Carry out the test within 5 h of preparation of solution S. Filter solution S on a membrane filter having approximately 0.45 μm pores rejecting the first few milliliters of filtrate. Measure the absorbance (2.2.25) of the filtrate at wavelengths from 220 nm to 360 nm using the blank (see solution S) as compensation liquid. At these wavelengths, the absorbance does not exceed 0.2 for type I closures or 4.0 for type II closures. If necessary, dilute the filtrate before measurement of the absorbance and correct the result for the dilution. [JP] Read the absorbance of the test solution between 220 nm and 350 nm against the blank solution as directed under Ultraviolet-visible Spectrophotometry <2.54>: it is not more than 0.20.[USP] Procedure — [NOTE—Perform this test within 5 hours of preparing Solution S.] Filter Solution S through a 0.45-µm pore size filter, discarding the first few mL of filtrate. Measure the absorbance of the filtrate at wavelengths between 220 and 360 nm in a 1-cm cell using the blank in a matched cell in the reference beam. If dilution of the filtrate is required before measurement of the absorbance, correct the test results for the dilution.Requirement—The absorbances at these wavelengths do not exceed 0.2 for Type I closures or 4.0 for Type II closures.11、Reducing Substances[YBB] To 20.0 mL of solution S add 1 mL of dilute sulfuric acid R and 20.0 mL of0.002 M potassium permanganate. Boil for 3 min. Cool. Add 0.1 g of potassiumiodide R and titrate immediately with 0.01 M sodium thiosulfate until the colorturned light brown , using 5 drops of starch solution R as indicator. Carry out atitration using 20.0 mL of the blank. The difference between the titrationvolumes is not greater than7.0mL.[EP] Carry out the test within 4 h of preparation of solution S. To 20.0 ml of solution S add 1 ml of dilute sulphuric acid R and 20.0 ml of 0.002 M potassium permanganate. Boil for 3min. Cool. Add 1 g of potassium iodide R and titrate immediately with 0.01 M sodium thiosulphate, using 0.25 ml of starch solution R as indicator. Carry out a titration using 20.0 ml of the blank. The difference between the titration volumes is not greater than 3.0 ml for type I closures and7.0 ml for type II closures.[JP] Measure 100 mL of the test solution in a glass-stoppered,Erlenmyer flask, add10.0 mL of 0.002 mol/L potassium permanganate VS and 5 mL of dilutesulfuric acid, and boil for 3 minutes. After cooling, add 0.10 g of potassium iodide,stopper, mix by shaking, then allow to stand for 10 minutes,and titrate<2.50> with 0.01 mol/L sodium thiosulfate VS(indicator: 5 drops of starch TS).Perform the blank test in the same manner, using 100 mL of the blank solution.The difference in mL of 0.002 mol/L potassium permanganate VS required between the tests is not more than 2.0 mL.[USP] Procedure— [NOTE—Perform this test within 4 hours of preparing Solution S.] To 20.0 mL of Solution S add 1 mL of diluted sulfuric acid and 20.0 mL of0.002 M potassium permanganate. Boil for 3 minutes. Cool, add 1 g ofpotassium iodide, and titrate immediately with 0.01 M sodium thiosulfate, using0.25 mL of starch solution TS as the indicator. Perform a titration using 20.0mL of blank and note the difference in volume of 0.01 M sodium thiosulfaterequired.Requirement—The difference between the titration volumes is not greater than 3.0 mL for Type I closures and not greater than 7.0 mL for Type II closures.12、Residue on evaporation[YBB]Evaporate 100 mL of solution S and blank solution to dryness on a water-bath and dry at 100 °C to 105 °C. The residue weighs not more than 4.0 mg. [EP]Evaporate 50.0 ml of solution S to dryness on a water-bath and dry at 100 °C to 105 °C. The residue weighs not more than 2.0 mg for type I rubber and notmore than 4.0 mg for type II rubber.[JP]Measure 100 mL of the test solution, evaporate on a water bath to dryness, and dry the residue at 1059 C for 1 hour.The mass of the residue is not morethan 2.0 mg.[USP]None13、Ammonium[YBB] Precision measuring 10 ml of solution S, adding alkaline potassium iodide solution 2 ml, place 15 minutes, should not be color; if it colored , compare with reference solution (with 2.0 ml ammonium chloride solution (take ammoniumchloride 31.5 mg, add right amount chlorine free water and dissolve diluted to1000 ml), 8 ml blank reference solution, 2ml alkaline potassium mercuric iodide solution for mixing), should not be more intensely colored (0.0002%)[EP] maximum 2 ppm.Dilute 5 ml of solution S to 14 ml with water R. The solution complies with limit test A.[JP]None[USP] Alkaline Potassium Tetraiodomercurate Solution— Prepare a 100 mL solution containing 11 g of potassium iodide and 15 g of mercuric iodide in water.Immediately before use, mix 1 volume of this solution with an equal volume ofa 250 g per L solution of sodium hydroxide.Test Solution— Dilute 5 mL of Solution S to 14 mL with water. Make alkaline if necessary by adding 1 N sodium hydroxide, and dilute with water to 15 mL.Add 0.3 mL of Alkaline Potassium Tetraiodomercurate Solution, and close the container.Ammonium Standard Solution— Prepare a solution of ammonium chloride in water (1 ppm NH4). Mix 10 mL of the 1 ppm ammonium chloride solution with5 mL water and 0.3 mL of Alkaline Potassium Tetraiodomercurate Solution.Close the container.Requirement—After 5 minutes, any yellow color in the Test Solution is no darker than the Ammonium Standard Solution (no more than 2 ppm of NH4 in Solution S).14、Extractable Zinc[YBB] Filter solution S on a membrane filter having approximately 0.45μm pores, Precision measuring filtrate 10 ml, add 1 ml 2 mol/L of hydrochloric acid and 3 drops of potassium ferrocyanide test solution(weight 4.2 g potassium ferrocyanide trihydrate, dissolve and diluted with water to 100 ml, shake evenly, this product should be new prepared) for mixing, should not be color; if it colored, compare with reference solution( with 3 ml standard zinc solution (weight 44.0g Zinc sulfate seven hydrated compounds, with new boiled and cooled purified water dissolved and diluted to 1000 ml, this product should be new prepared), shall not be deeper(0.0002%),7ml blank reference solution, 1ml 2mol/L hydrochloric acid and 3 drops of potassium ferrocyanide solution for mixing), should not be more intensely colored.(0.0003%)[EP] maximumof 5 μg of extractable Zn per millilitre of solution S.Atomic absorption spectrophotometry (2.2.23, Method I). Test solution. Dilute10.0 ml of solution S to 100 ml with 0.1 M hydrochloric acid.Reference solutions. Prepare the reference solutions using zinc standard solution(10 ppm Zn) R diluted with 0.1 M hydrochloric acid.Source: zinc hollow-cathode lamp.Wavelength: 213.9 nm.Flame: air-acetylene.[JP]To 10.0 mL of the test solution add diluted dilute nitric acid (1 in 3) to make 20 mL, and use this solution as the sample solution. Further, to 1.0 mL of Standard Zinc Solutionfor atomic absorption spectrophotometry add diluted nitricacid (1 in 3) to make exactly 20 mL, and use this solution asthe standard solution. Perform the tests according to the Atomic Absorption Spectrophotometry <2.23>,using these solutions, under the following conditions.The absorbanceof the sample solution is not more than that of the standardsolution.Gas: Combustible gasóAcetylene.Supporting gasóAir.Lamp: Zinc hollow-cathode lamp.Wavelength: 213.9 nm.Standard Zinc Solution for atomic absorption spectrophotometry: Measure exactly 10 mL of the Standard Zinc Stock Solution, and add water to make exactly 1000 mL. Prepare before use. One mL of this solution contains 0.01 mg of zinc(Zn).[USP] Test Solution—Prepare a Test Solution by diluting 10.0 mL of Solution S to 100 mL with 0.1N hydrochloric acid. Prepare a test blank similarly, using the Blank forSolution S.Zinc Standard Solution— Prepare a solution (10 ppm Zn) by dissolving zinc sulfate in 0.1 N hydrochloric acid.Reference Solutions—Prepare not fewer than 3 Reference Solutions by diluting the Zinc Standard Solution with 0.1 N hydrochloric acid. The concentrations of zinc in these Reference Solutions are to span the expected limit of the Test Solution.Procedure—Use a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light Scattering 851 ) equipped with a zinc hollow-cathode lamp and an air–acetylene flame. An alternative procedure such as an appropriately validated inductively coupled plasma analysis (ICP) may be used.Test each of the Reference Solutions at the zinc emission line of 213.9 nm at least 3 times. Record the steady readings. Rinse the apparatus with the test blank solution each time, to ensure that the reading returns to initial blank value.Prepare a calibration curve from the mean of the readings obtained for each Reference Solution. Record the absorbance of the Test Solution. Determine the ppm zinc concentration of the Test Solution using the calibration curve.Requirement— Solution S contains not more than 5 ppm of extractable zinc.15、Cadmium[YBB]None[EP]None[JP]Wash the rubber closures with water, dry at room temperature, cut into minute pieces, mix well, place 2.0 g of them in a crucible of platinum or quartz, moisten them with 2 mL of sulfuric acid, heat gradually to dryness, and ignite between 4509 Cand5009 C until the residue is incinerated. When in cineration was insufficient, moisten the residue with 1 mL of sulfuric acid, heat to dryness, and ignite again. Repeat the above-mentioned procedure if necessary. Cool the crucible,moisten the residue with water, add 2 to 4 mL of hydrochloric acid, heat on a water bath to dryness, add 1 to 5 mL of hydrochloric acid, and dissolve by heating. Then add 0.5 to 1 mL of a mixture of a solution of citric acid monohydrate (1 in 2) and hydrochloric acid (1:1) and 0.5 to 1 mL of a warmed solution of ammonium acetate (2 in 5). When any insoluble residue remains, filter through a glass filter. To the solution thus obtained add 10 mL ofa solution of diammonium hydrogen citrate (1 in 4), 2 drops of bromothymolblue TS and ammonium TS until the color of the solution changes from yellow to green. Then add 10 mL of ammonium sulfate solution (2 in 5) and water to make 100 mL. Next, add 20 mL of a solution of sodium N,N-diethyldithiocarbamate trihydrate (1 in 20), mix, allow to stand for a few minutes,add 20.0 mL of 4-methyl-2-pentanone, and mix by vigorous shaking.Allow to stand to separate the 4-methyl-2-pentanone layer from the solution, filter if necessary, and use as the sample solution. On the other hand, to 10.0 mL of Standard Cadmium Solution add 10 mL of a solution of diammonium hydrogen citrate (1 in 4) and 2 drops of bromothymol blue TS, proceed in the same manner as for the sample solution, and use this solution as the standard solution.Perform the tests according to the Atomic Absorption Spectrophotometry <2.23> under the following conditions, using the sample solution and the standard solution. The absorbance of the sample solution is notmore than that of thestandard solution.Gas: Combustible gas—Acetylene or hydrogen.Supporting gas—Air.Lamp: Cadmium hollow-cathode lamp.Wavelength: 228.8 nm.[USP] None。

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