3.2.9.注射用粉针和冻干粉末容器胶塞标准
3.2.9. RUBBER CLOSURES FOR CONTAINERS FOR AQUEOUS
PARENTERAL PREPARATIONS, FOR POWDERS AND FOR
FREEZE-DRIED POWDERS
粉和冻干粉水肠外制剂胶塞材料通过高分子物质（弹性体）硫化（交联），加入合适的添加剂获得。该规范也适用于粉和冻干粉在使用前立即被溶解在水中的封闭容器。该规范不适用于硅橡胶制成的胶塞（在3.1.9处理，不封和油管的有机硅弹性体），夹层封闭或漆封。弹性体由天然胶或合成物质的聚合，加聚或缩聚产生。主要组成部分和各种添加剂的性质（例如硫化剂、促进剂、稳定剂、色素）取决于成品所需的属性。
Rubber closures for containers for aqueous parenteral preparations for powders and for freeze-dried powders are made of materials obtained by vulcanisation (cross-linking) of macromolecular organic substances (elastomers), with appropriate additives. The specification also applies to closures for containers for powders and freeze-dried products to be dissolved in water immediately before use.The specification does not apply to closures made from silicone elastomer (which are dealt with in 3.1.9. Silicone elastomer for closures and tubing), to laminated closures or to lacquered closures. The elastomers are produced from natural or synthetic substances by polymerisation, polyaddition or polycondensation. The nature of the principal components and of the various additives (for example vulcanisers, accelerators, stabilisers, pigments) depends on the properties required for the finished article.
胶塞材料可以分为两类：Ⅰ类胶塞符合严格要求，是首选；Ⅱ类胶塞有着适用于特殊用途（如多孔冲孔）的机械性能，但因为它们的化学组成，不能满足第一类那样的需求。
Rubber closures may be classified in 2 types : type I closures are those which meet the strictest requirements and which are to be preferred; type II closures are those which, having mechanical properties suitable for special uses (for example, multiple piercing), cannot meet requirements as severe as those
for the first category because of their chemical composition.
供特殊制备使用选择的胶塞如：
—与胶塞相关的制备部件不能吸附到胶塞的表面，不能迁移或通过胶塞的表面而影响制备。
—胶塞成批的不屈服的准备物质的数量足以影响其稳定性或目前的毒性风险。
The closures chosen for use with a particular preparation are such that : —the components of the preparation in contact with the closure are not adsorbed onto the surface of the closure and do not migrate into or through the closure to an extent sufficient to affect the preparation adversely,
— the closure does not yield to the preparation substances in
quantities sufficient to affect its stability or to present a risk of
toxicity.
胶塞与它们使用其整个有效期的准备兼容。该制剂的制造商必须从供应商获得保证，胶塞的组成不发生变化，这是相同的兼容性测试期间使用的封闭。当供应商通知制造商编制的构成变化时，兼容性实验必须重复，全部或部分，视变化的性质而定。
胶塞在使用前必须经过清洗和消毒。
The closures are compatible with the preparation for which they are used throughout its period of validity. The manufacturer of the preparation must obtain from the supplier an assurance that the composition of the closure does not vary and that it is identical to that of the closure used during compatibility testing. When the supplier informs the manufacturer of the preparation of changes in the composition, compatibility testing must be repeated, totally or partly, depending on the nature of the changes.
The closures are washed and may be sterilised before use.
特征CHARACTERS
橡胶塞是弹性的；它们是透明的或不透明的，没有特有的颜色，后者随所使用的添加剂的颜色而定。它们几乎不溶于四氢呋喃，但是，在其中可能发生相当多的可逆溶胀。它们是同类的，基本上是于闪光灯和不定材料分离出来（如纤维、杂质颗粒、废旧橡胶）。
Rubber closures are elastic ; they are translucent or opaque and have no characteristic colour, the latter depending on the additives used. They are practically insoluble in tetrahydrofuran, in which, however, a considerable reversible swelling may occur. They are homogeneous and practically free from flash and adventitious materials (for example fibres, foreign particles, waste rubber).
胶塞类型的橡胶的鉴定不属于本规范的范围。下面给出鉴定试验区分弹性体和非弹性体，但不区分各类橡胶。一个批次的用于兼容性试验的闭包，其差异性可用其它鉴定测验检测。一种或多种一下的分析方法可用于此目的：相对密度测定，硫酸盐灰分测定，含硫量测定，提炼物的薄色层分离法，干馏物的红外分光光度测量。
Identification of the type of rubber used for the closures is not within the scope of this specification. The identification test given below distinguishes elastomer and non-elastomer closures but does not differentiate the various types of rubber. Other identity tests may be carried out with the aim of detecting differences in a batch compared to the closures used for compatibility testing. One or more of the following analytical methods may be applied for this purpose: determination of relative density, determination of sulphated ash, determination of sulphur content, thin-layer chromatography carried out on an extract, ultraviolet absorption spectrophotometry of an extract, infrared absorption spectrophotometry of a pyrolysate.
鉴定IDENTIFICATION
A. 弹性体是这样一种材料，由专人可以将一个横截面1～5mm2拉伸至至
少原长的两倍。保持原长两倍一分钟，它可以在30秒内恢复到原长的1.2倍。
B.热1～2g的试样，在耐热的试管里放于明火上干燥，并继续加热至热解蒸汽凝结在试管顶部边缘附近。放少量的干馏物在溴化钾压片上，通过红外分光光度法测量（2.2.24），同所获得的试样光谱比较。
C.结果的总灰分（2.4.16）在±10%以内为标准样品。
A. The elasticity is such that a strip of material with a cross-section of 1 mm2 to 5 mm2 can be stretched by hand to at least twice its original length. Having been stretched to twice its length for l min, it contracts to less than
1.2 times its original length within 30 s.
B. Heat 1 g to 2 g in a heat-resistant test-tube over an open flame to dry the sample and continue heating until pyrolysate vapours are condensed near the top edge of the test-tube. Deposit a few drops of the pyrolysate on a potassium bromide disc and examine by infrared absorption spectrophotometry (2.2.24), comparing with the spectrum obtained with the type sample.
C. The total ash (2.4.16) is within ± 10 per cent of the result obtained with the type sample.
检测TESTS
分析样品使用前须经清洗和灭菌。
The samples to be analysed may be washed and sterilized before use. 饱和溶液。引进许多相当于表面积大约100m2大小的玻璃容器上的合适的胶塞，填满注射用水，煮沸5分钟并用注射用水冲洗5次。将清洗过的塞子放在广口瓶上(Ⅰ类玻璃，3.2.1)，加200mL注射用水，称重。用硼硅酸盐玻璃杯盖住烧瓶口。高压灭菌器中加热使得在20～30分钟内达到121±2℃的温度，保持30分钟以上。注射用水优化原质量。摇动并立即以移注法分离橡胶与溶液。每次测试前摇动饱和溶液。
空白溶液。同样方法制备200mL的注射用水空白溶液。
Solution S. Introduce a number of uncut closures corresponding to a surface area of about 100 cm2 in 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 30 min. 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 test
Blank. Prepare a blank in the same manner using 200 ml of water for injections R.
溶液外观。饱和溶液的乳白色较Ⅰ类胶塞的参比悬液Ⅱ和Ⅱ类胶塞（2.2.1）的参比悬液Ⅲ的颜色浅，没有GY5（2.2.2，方法Ⅱ）溶液的外观颜色强烈。
Appearance of solution. 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).
酸碱度。在20ml的饱和溶液中滴加0.1mL的百里酚蓝溶液1。加不多于0.3ml的0.01mol/l的氢氧化钠溶液或0.8ml的0.01mol/l的盐酸溶液分别得到蓝色或黄色。
Acidity or alkalinity. 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.
吸光度。5小时内测试制备好的饱和溶液。在0.45μm虑孔的薄膜滤器上过滤饱和溶液，弃掉少部分滤液。以空白液（见饱和溶液）作为补偿，在220～300nm波长处检测滤出液的吸光度（2.2.25）。在那些波长范围内，Ⅰ类胶塞的吸光度没有超过0.2，Ⅱ类胶塞没有超过4.0。如必要，测量吸光度前稀释滤出液，将结果加以改正。
Absorbance. 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.
还原物质。4小时内测试制备好的饱和溶液。在20.0ml的饱和溶液中加入1ml的稀释硫酸盐和20.0ml的0.002mol/l高锰酸钾。煮沸3分钟。冷却。加1g的碘化钾，立即用0.01mol/l的硫代硫酸钠滴定，用0.25ml的淀粉溶液作指示剂。用20.0mL的空白溶液完成滴定。Ⅰ类胶塞滴定体积的差别不大于3.0ml，Ⅱ类胶塞不大于7.0ml。
Reducing substances. 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 and 7.0 ml for type II closures.
铵（2.4.1）：最大量2ppm
将5ml的饱和溶液注射水稀释至14ml。溶液遵循限度检查A。Ammonium (2.4.1) : maximum 2 ppm.
Dilute 5 ml of solution S to 14 ml with water R. The solution complies with limit test A.
可萃取锌：饱和溶液中萃取锌最大量5μg/ml。
原子吸收分光光度法（方法Ⅱ，2.2.23）。测量溶液。0.1mol/l的盐酸溶液将10.0ml的饱和溶液稀释至100ml。
参比溶液。以0.1mol/l的盐酸稀释锌标准溶液（10ppm Zn）制备参比溶液。 来源：锌空心阴极电子管。
波长：213.9nm。
火焰：空心乙炔焊。
Extractable zinc: maximumof 5 μg of extractable Zn per millilitre of solution
S.
Atomic absorption spectrophotometry (2.2.23, Method I). Test solution. Dilute 10.0 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.
可萃取重金属（2.4.8）。最大量2ppm
饱和溶液遵循限度检查A。铅标准溶液（2ppm Pb）制备标准液。
Extractable heavy metals (2.4.8) : maximum 2 ppm.
Solution S complies with limit test A. Prepare the standard using lead standard solution (2 ppm Pb) R.
蒸发残余物。水浴锅中蒸发50.0mL的标准溶液并从100℃干燥到105℃。Ⅰ类橡胶剩余残渣重量不多于2.0mg，Ⅱ类橡胶不多于4.0mg。
Residue on evaporation. 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 not more than 4.0 mg for type II rubber.
挥发性硫化物。将20±2cm2表面积的胶塞（必要时切割）放入100ml锥形瓶中，加50ml 20g/l的柠檬酸R。同时用0.154mg硫化钠R和50ml 20g/l 柠檬酸R在100ml锥形瓶中配得标准溶液。分别在锥形瓶口上方放一张醋酸铅试纸，将倒置的称量瓶放在试纸上以使之固定。将锥形瓶放入高压蒸汽灭菌器，在121±2℃加热30分钟。试纸上的任何黑色痕迹都不能比标准溶液上的试纸颜色强。
为渗透性、分裂和自密封测试，使用的胶塞经过精心处理，并将其干燥。 Volatile sulphides. 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 °C 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.
For the tests for penetrability, fragmentation and self-sealing, use the closures treated as described for the preparation of solution S and allowed to dry.
穿刺力。拟通过皮下注射针头穿透胶塞，开展了以下测试。注射水填充10个适当大小的试剂瓶至标称体积，给塞子配置适合检验且安全的帽子。作为新塞子使用，润滑长锥（1）（斜角12±2°）的外径0.8mm的皮下注射器针头，垂直刺穿胶塞。穿刺力的精度在±0.25N, 数值不大于10N。
Penetrability. For closures intended to be pierced by a hypodermic needle, 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, 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.
穿刺落屑。拟通过皮下注射针头穿透胶塞，开展了以下测试。如果胶塞是应用于水制剂，在12个干净小瓶内注入比标称容积少4ml的水，盖上胶塞，封盖，保持16小时。如果胶塞应用于干粉制剂，在12个小瓶上盖上胶塞以待检测。用与针筒匹配的外径0.8mm的润滑长锥（1）（斜角12±2°）形皮下注射器针头，注入1ml水，并抽出1ml的空气；每个胶塞穿刺四次，且穿刺位置不同，每个胶塞穿刺完后都应使用一个新的针头，并检查在测试期间针头是否变钝。将瓶中液体倒入孔径为0.5μm的滤膜过滤，数肉眼可见的橡胶落屑数，落屑总数不超过5个。此限制是基于这样的假设，落屑的直径为肉眼可见的等于或大于50μm；若有怀疑或争议，落屑可用显微镜检查，以验证它的性质和大小。
Fragmentation. 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 in 12 clean vials a volume of water R corresponding to the nominal volume minus 4 ml, close the vials with the closures to be examined, secure with a cap and allow 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 approximately 0.5 μm pores. Count the fragments of rubber visible to the naked eye. The total number of fragments does not exceed
5. This limit is based on the assumption that fragments with a diameter equal to or 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.
自密封性测试。拟使用多剂量容器的胶塞，开展了以下测试。在10个合适的小瓶中注入水R至标称体积，盖上待测胶塞，封盖。每个胶塞使用一个新的外径为0.8 mm的注射针头穿透10次，每次在不同部位。将小瓶垂直浸入1g/l的亚甲基蓝R，减少外部压力27千帕，维持10分钟。恢复大气压强，小瓶继续浸没30分钟。冲洗小瓶的外表面，亚甲基蓝R不得渗入瓶内。
Self-sealing test. 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.
3.2.9.注射用粉针和冻干粉末容器胶塞标准
3.2.9. RUBBER CLOSURES FOR CONTAINERS FOR AQUEOUS
PARENTERAL PREPARATIONS, FOR POWDERS AND FOR
FREEZE-DRIED POWDERS
粉和冻干粉水肠外制剂胶塞材料通过高分子物质（弹性体）硫化（交联），加入合适的添加剂获得。该规范也适用于粉和冻干粉在使用前立即被溶解在水中的封闭容器。该规范不适用于硅橡胶制成的胶塞（在3.1.9处理，不封和油管的有机硅弹性体），夹层封闭或漆封。弹性体由天然胶或合成物质的聚合，加聚或缩聚产生。主要组成部分和各种添加剂的性质（例如硫化剂、促进剂、稳定剂、色素）取决于成品所需的属性。
Rubber closures for containers for aqueous parenteral preparations for powders and for freeze-dried powders are made of materials obtained by vulcanisation (cross-linking) of macromolecular organic substances (elastomers), with appropriate additives. The specification also applies to closures for containers for powders and freeze-dried products to be dissolved in water immediately before use.The specification does not apply to closures made from silicone elastomer (which are dealt with in 3.1.9. Silicone elastomer for closures and tubing), to laminated closures or to lacquered closures. The elastomers are produced from natural or synthetic substances by polymerisation, polyaddition or polycondensation. The nature of the principal components and of the various additives (for example vulcanisers, accelerators, stabilisers, pigments) depends on the properties required for the finished article.
胶塞材料可以分为两类：Ⅰ类胶塞符合严格要求，是首选；Ⅱ类胶塞有着适用于特殊用途（如多孔冲孔）的机械性能，但因为它们的化学组成，不能满足第一类那样的需求。
Rubber closures may be classified in 2 types : type I closures are those which meet the strictest requirements and which are to be preferred; type II closures are those which, having mechanical properties suitable for special uses (for example, multiple piercing), cannot meet requirements as severe as those
for the first category because of their chemical composition.
供特殊制备使用选择的胶塞如：
—与胶塞相关的制备部件不能吸附到胶塞的表面，不能迁移或通过胶塞的表面而影响制备。
—胶塞成批的不屈服的准备物质的数量足以影响其稳定性或目前的毒性风险。
The closures chosen for use with a particular preparation are such that : —the components of the preparation in contact with the closure are not adsorbed onto the surface of the closure and do not migrate into or through the closure to an extent sufficient to affect the preparation adversely,
— the closure does not yield to the preparation substances in
quantities sufficient to affect its stability or to present a risk of
toxicity.
胶塞与它们使用其整个有效期的准备兼容。该制剂的制造商必须从供应商获得保证，胶塞的组成不发生变化，这是相同的兼容性测试期间使用的封闭。当供应商通知制造商编制的构成变化时，兼容性实验必须重复，全部或部分，视变化的性质而定。
胶塞在使用前必须经过清洗和消毒。
The closures are compatible with the preparation for which they are used throughout its period of validity. The manufacturer of the preparation must obtain from the supplier an assurance that the composition of the closure does not vary and that it is identical to that of the closure used during compatibility testing. When the supplier informs the manufacturer of the preparation of changes in the composition, compatibility testing must be repeated, totally or partly, depending on the nature of the changes.
The closures are washed and may be sterilised before use.
特征CHARACTERS
橡胶塞是弹性的；它们是透明的或不透明的，没有特有的颜色，后者随所使用的添加剂的颜色而定。它们几乎不溶于四氢呋喃，但是，在其中可能发生相当多的可逆溶胀。它们是同类的，基本上是于闪光灯和不定材料分离出来（如纤维、杂质颗粒、废旧橡胶）。
Rubber closures are elastic ; they are translucent or opaque and have no characteristic colour, the latter depending on the additives used. They are practically insoluble in tetrahydrofuran, in which, however, a considerable reversible swelling may occur. They are homogeneous and practically free from flash and adventitious materials (for example fibres, foreign particles, waste rubber).
胶塞类型的橡胶的鉴定不属于本规范的范围。下面给出鉴定试验区分弹性体和非弹性体，但不区分各类橡胶。一个批次的用于兼容性试验的闭包，其差异性可用其它鉴定测验检测。一种或多种一下的分析方法可用于此目的：相对密度测定，硫酸盐灰分测定，含硫量测定，提炼物的薄色层分离法，干馏物的红外分光光度测量。
Identification of the type of rubber used for the closures is not within the scope of this specification. The identification test given below distinguishes elastomer and non-elastomer closures but does not differentiate the various types of rubber. Other identity tests may be carried out with the aim of detecting differences in a batch compared to the closures used for compatibility testing. One or more of the following analytical methods may be applied for this purpose: determination of relative density, determination of sulphated ash, determination of sulphur content, thin-layer chromatography carried out on an extract, ultraviolet absorption spectrophotometry of an extract, infrared absorption spectrophotometry of a pyrolysate.
鉴定IDENTIFICATION
A. 弹性体是这样一种材料，由专人可以将一个横截面1～5mm2拉伸至至
少原长的两倍。保持原长两倍一分钟，它可以在30秒内恢复到原长的1.2倍。
B.热1～2g的试样，在耐热的试管里放于明火上干燥，并继续加热至热解蒸汽凝结在试管顶部边缘附近。放少量的干馏物在溴化钾压片上，通过红外分光光度法测量（2.2.24），同所获得的试样光谱比较。
C.结果的总灰分（2.4.16）在±10%以内为标准样品。
A. The elasticity is such that a strip of material with a cross-section of 1 mm2 to 5 mm2 can be stretched by hand to at least twice its original length. Having been stretched to twice its length for l min, it contracts to less than
1.2 times its original length within 30 s.
B. Heat 1 g to 2 g in a heat-resistant test-tube over an open flame to dry the sample and continue heating until pyrolysate vapours are condensed near the top edge of the test-tube. Deposit a few drops of the pyrolysate on a potassium bromide disc and examine by infrared absorption spectrophotometry (2.2.24), comparing with the spectrum obtained with the type sample.
C. The total ash (2.4.16) is within ± 10 per cent of the result obtained with the type sample.
检测TESTS
分析样品使用前须经清洗和灭菌。
The samples to be analysed may be washed and sterilized before use. 饱和溶液。引进许多相当于表面积大约100m2大小的玻璃容器上的合适的胶塞，填满注射用水，煮沸5分钟并用注射用水冲洗5次。将清洗过的塞子放在广口瓶上(Ⅰ类玻璃，3.2.1)，加200mL注射用水，称重。用硼硅酸盐玻璃杯盖住烧瓶口。高压灭菌器中加热使得在20～30分钟内达到121±2℃的温度，保持30分钟以上。注射用水优化原质量。摇动并立即以移注法分离橡胶与溶液。每次测试前摇动饱和溶液。
空白溶液。同样方法制备200mL的注射用水空白溶液。
Solution S. Introduce a number of uncut closures corresponding to a surface area of about 100 cm2 in 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 30 min. 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 test
Blank. Prepare a blank in the same manner using 200 ml of water for injections R.
溶液外观。饱和溶液的乳白色较Ⅰ类胶塞的参比悬液Ⅱ和Ⅱ类胶塞（2.2.1）的参比悬液Ⅲ的颜色浅，没有GY5（2.2.2，方法Ⅱ）溶液的外观颜色强烈。
Appearance of solution. 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).
酸碱度。在20ml的饱和溶液中滴加0.1mL的百里酚蓝溶液1。加不多于0.3ml的0.01mol/l的氢氧化钠溶液或0.8ml的0.01mol/l的盐酸溶液分别得到蓝色或黄色。
Acidity or alkalinity. 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.
吸光度。5小时内测试制备好的饱和溶液。在0.45μm虑孔的薄膜滤器上过滤饱和溶液，弃掉少部分滤液。以空白液（见饱和溶液）作为补偿，在220～300nm波长处检测滤出液的吸光度（2.2.25）。在那些波长范围内，Ⅰ类胶塞的吸光度没有超过0.2，Ⅱ类胶塞没有超过4.0。如必要，测量吸光度前稀释滤出液，将结果加以改正。
Absorbance. 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.
还原物质。4小时内测试制备好的饱和溶液。在20.0ml的饱和溶液中加入1ml的稀释硫酸盐和20.0ml的0.002mol/l高锰酸钾。煮沸3分钟。冷却。加1g的碘化钾，立即用0.01mol/l的硫代硫酸钠滴定，用0.25ml的淀粉溶液作指示剂。用20.0mL的空白溶液完成滴定。Ⅰ类胶塞滴定体积的差别不大于3.0ml，Ⅱ类胶塞不大于7.0ml。
Reducing substances. 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 and 7.0 ml for type II closures.
铵（2.4.1）：最大量2ppm
将5ml的饱和溶液注射水稀释至14ml。溶液遵循限度检查A。Ammonium (2.4.1) : maximum 2 ppm.
Dilute 5 ml of solution S to 14 ml with water R. The solution complies with limit test A.
可萃取锌：饱和溶液中萃取锌最大量5μg/ml。
原子吸收分光光度法（方法Ⅱ，2.2.23）。测量溶液。0.1mol/l的盐酸溶液将10.0ml的饱和溶液稀释至100ml。
参比溶液。以0.1mol/l的盐酸稀释锌标准溶液（10ppm Zn）制备参比溶液。 来源：锌空心阴极电子管。
波长：213.9nm。
火焰：空心乙炔焊。
Extractable zinc: maximumof 5 μg of extractable Zn per millilitre of solution
S.
Atomic absorption spectrophotometry (2.2.23, Method I). Test solution. Dilute 10.0 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.
可萃取重金属（2.4.8）。最大量2ppm
饱和溶液遵循限度检查A。铅标准溶液（2ppm Pb）制备标准液。
Extractable heavy metals (2.4.8) : maximum 2 ppm.
Solution S complies with limit test A. Prepare the standard using lead standard solution (2 ppm Pb) R.
蒸发残余物。水浴锅中蒸发50.0mL的标准溶液并从100℃干燥到105℃。Ⅰ类橡胶剩余残渣重量不多于2.0mg，Ⅱ类橡胶不多于4.0mg。
Residue on evaporation. 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 not more than 4.0 mg for type II rubber.
挥发性硫化物。将20±2cm2表面积的胶塞（必要时切割）放入100ml锥形瓶中，加50ml 20g/l的柠檬酸R。同时用0.154mg硫化钠R和50ml 20g/l 柠檬酸R在100ml锥形瓶中配得标准溶液。分别在锥形瓶口上方放一张醋酸铅试纸，将倒置的称量瓶放在试纸上以使之固定。将锥形瓶放入高压蒸汽灭菌器，在121±2℃加热30分钟。试纸上的任何黑色痕迹都不能比标准溶液上的试纸颜色强。
为渗透性、分裂和自密封测试，使用的胶塞经过精心处理，并将其干燥。 Volatile sulphides. 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 °C 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.
For the tests for penetrability, fragmentation and self-sealing, use the closures treated as described for the preparation of solution S and allowed to dry.
穿刺力。拟通过皮下注射针头穿透胶塞，开展了以下测试。注射水填充10个适当大小的试剂瓶至标称体积，给塞子配置适合检验且安全的帽子。作为新塞子使用，润滑长锥（1）（斜角12±2°）的外径0.8mm的皮下注射器针头，垂直刺穿胶塞。穿刺力的精度在±0.25N, 数值不大于10N。
Penetrability. For closures intended to be pierced by a hypodermic needle, 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, 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.
穿刺落屑。拟通过皮下注射针头穿透胶塞，开展了以下测试。如果胶塞是应用于水制剂，在12个干净小瓶内注入比标称容积少4ml的水，盖上胶塞，封盖，保持16小时。如果胶塞应用于干粉制剂，在12个小瓶上盖上胶塞以待检测。用与针筒匹配的外径0.8mm的润滑长锥（1）（斜角12±2°）形皮下注射器针头，注入1ml水，并抽出1ml的空气；每个胶塞穿刺四次，且穿刺位置不同，每个胶塞穿刺完后都应使用一个新的针头，并检查在测试期间针头是否变钝。将瓶中液体倒入孔径为0.5μm的滤膜过滤，数肉眼可见的橡胶落屑数，落屑总数不超过5个。此限制是基于这样的假设，落屑的直径为肉眼可见的等于或大于50μm；若有怀疑或争议，落屑可用显微镜检查，以验证它的性质和大小。
Fragmentation. 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 in 12 clean vials a volume of water R corresponding to the nominal volume minus 4 ml, close the vials with the closures to be examined, secure with a cap and allow 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 approximately 0.5 μm pores. Count the fragments of rubber visible to the naked eye. The total number of fragments does not exceed
5. This limit is based on the assumption that fragments with a diameter equal to or 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.
自密封性测试。拟使用多剂量容器的胶塞，开展了以下测试。在10个合适的小瓶中注入水R至标称体积，盖上待测胶塞，封盖。每个胶塞使用一个新的外径为0.8 mm的注射针头穿透10次，每次在不同部位。将小瓶垂直浸入1g/l的亚甲基蓝R，减少外部压力27千帕，维持10分钟。恢复大气压强，小瓶继续浸没30分钟。冲洗小瓶的外表面，亚甲基蓝R不得渗入瓶内。
Self-sealing test. 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.