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美国药典·G1 ⼆甲基聚硅氧烷油（Dimethylpolysiloxaneoil) ov-101G4 聚⼆⼄⼆醇丁⼆酸酯DEGS·G2 ⼆甲基聚硅烷胶（Dimethylpolysiloxane Gum)ov-1 ·G3 50%苯基-50%甲基聚硅氧烷(50% Phenyl-50% methylpo..ov-17·G5 3-氰丙基聚氧硅烷·G6 三氟丙基甲基聚硅氧烷·G7 50%-3-氰丙基聚硅氧烷-50%苯甲基硅氧烷·G8 90％3氰基丙基－10％苯基甲基聚硅氧烷·G9 甲基⼄烯基聚硅氧烷·G10 聚酰胺·G11 双（2⼄基⼰基）癸⼆酸聚酯·G12 苯基⼆⼄醇胺琥珀酸聚酯·G13 ⼭梨醇·G14 聚⼄⼆醇（平均分⼦量950－1050）·G15 聚⼄⼆醇（平均分⼦量3000－3700）·G16 聚⼄⼆醇（平均分⼦量15,000）·G17 75% 苯基- 25% 甲基聚硅氧烷·G18 聚亚烷基⼆醇·G19 25% 苯基- 25% 氰丙基甲基聚硅氧烷·G20 聚⼄⼆醇（平均分⼦量380-420）·G21 丁⼆酸新戊⼆醇酯（NGS）·G22 双（2-⼄基⼰基）邻苯⼆甲酸酯·G23 聚⼰⼆酸⼄⼆醇酯 EGA·G24 ⼆异癸邻苯⼆甲酸酯·G25 聚⼄⼆醇TPA（Carbowax 20M 对苯⼆酸）·G26 25％2-氰基⼄基－75％甲基聚硅氧烷·G27 5% 苯基- 95% 甲基聚硅氧烷·G28 25% 苯基- 75% 甲基聚硅氧烷·G29 3,3’-硫代丙晴 TDPN·G30 四⽢醇⼆甲基醚·G31 Nonylphenoxypoly(ethyleneoxy)ethanol·G32 20% Phenylmethyl-80%dimethylpolysiloxane.·G33 20% Carborane-80% methylsilicone.·G34 Diethylene glycol succinatepolyester stabili..·G35 聚⼄⼆醇和硝基对苯⼆甲酸⼆⼄⼆醇酯·G36 1% ⼄烯基- 5% 苯基甲基聚硅氧烷·G37 Polyimide.·G38 固定相G1 加减尾剂·G39 聚⼄⼆醇（平均分⼦量15,00）·G40 Ethylene glycol adipate.（EGA）·G41 苯基甲基⼆甲基聚硅氧烷（被10% 苯基取代）·G42 35% 苯基- 65% ⼆甲基⼄烯聚硅氧烷·G43 6% 氰丙基苯基- 94% ⼆甲基聚硅氧烷·G44 2% low molecular weightpetrolatum hydrocarbo..·G45 ⼆⼄烯基苯-⼄⼆醇-⼆甲基丙烯酸酯·G46 14% 氰丙基苯基- 86% 甲基聚硅氧烷·G47 Polyethylene glycol (av. mol. wt. of about 80..·G48 Highly polar, partially cross-linked cyanopol..。
⽢油--药典性状：本品为⽆⾊、澄清的粘稠液体；味甜，有引湿性，⽔溶液（1→10）显中性反应本品与⽔或者⼄醇能任意混溶，在丙酮中微溶，在三氯甲烷或⼄醚中均不容。
相对密度：本品的相对密度（附录ⅥA），在25℃时不⼩于1.2569鉴别：本品的红外吸收图谱应与对照的谱图（光谱集77图）⼀致检查：1.颜⾊取本品50ml，置50ml纳式⽐⾊管中，与对照液（取⽐⾊⽤重铬酸钾溶液0.2ml，加⽔稀释⾄50ml制成）⽐较，不得更深。
2.氯化物：取本品5.0g，依法检查（附录ⅧA），与标准氯化钠溶液7.5ml制成的对照液⽐较，不得更浓（0.0015%）。
3.硫酸盐：取本品10g，依法检查（附录ⅧB），与标准硫酸钾溶液2.0ml制成的对照液⽐较，不得更浓（0.002%）。
4.脂肪酸与酯类：取本品40g，加新沸过的冷⽔40ml，再精密加氢氧化钠滴定液（0.1mol/L）10ml，摇匀后，煮沸5分钟，放冷，加酚酞指⽰液数滴，⽤盐酸滴定液（0.1mol/L）滴定剩余的氢氧化钠，并将滴定的结果⽤空⽩试验校正，消耗的氢氧化钠滴定液（0.1mol/L）不得过4.0ml。
5.丙烯醛、葡萄糖与铵盐：取本品4.0g，加10%氢氧化钾溶液5ml，混匀，在60℃放置5分钟，不得显黄⾊或发⽣氨臭。
6.易碳化物取本品4.0g，照易碳化物检查法（附录ⅧO）项下⽅法检查，静置时间为1⼩时，如显⾊，与对照溶液（取⽐⾊⽤氯化钴溶液0.2ml、⽐⾊⽤重铬酸钾溶液1.6ml与⽔8.2ml制成）⽐较，不得更深。
7.⼆⽢醇、⼄⼆醇和其他杂质取本品约10g，精密称定，置25ml量瓶中，精密加⼊内标溶液（每1ml中含0.5mg正⼰醇的甲醇溶液）5ml，⽤甲醇溶解并稀释⾄刻度，作为供试品溶液。
取⼆⽢醇、⼄⼆醇适量，精密称定，⽤甲醇溶解并稀释制成每1ml中含有⼆⽢醇、⼄⼆醇各0.5mg的溶液。
精密量取5ml，置25ml量瓶中，精密加⼊内标溶液5ml，⽤甲醇稀释⾄刻度，作为对照品溶液。
美国药典简介1. 标题和修订（Title and Revision）. 92. 药典地位和法律认可（Official status and legal recognition）92.10 药典正文(Official Text) 92.20 药典物品（Official Articles）. 92.30 法律认可（Legal Recognition）. 103. 与标准的符合性（Conformance to standard）. 103.10 标准的适用性 (Applicability of standard) 103.10.10 制剂、原料药、辅料的标准的适用性（Applicability of Standards to Drug Products, Drug Substances, and Excipients）. 103.10.20 医疗器械、营养补充剂、以及其组成成分的标准的适用性（Applicability of Standards to Medical Devices, Dietary Supplements, and Their Components and Ingredients）113.20 一致性的标示（Indicating Conformance）. 114. 药典各论和通则（Monographs and general chapters）124.10 各论(Monographs) 124.10.10 检测程序的适用性(Applicability of Test Procedures) 124.10.20 接受标准(Acceptance Criteria) 124.20 附录（General Chapter）. 125. 各论组成（Monograph Components）. 135.10 分子式（Molecular formula）. 135.20 附加物质、赋形剂、组分(Added Substances, Excipients, and Ingredients) 135.20.10官方原料药中附加的物质、赋形剂、组分（Added Substances, Excipients, and Ingredien ts in Official Substances）. 135.20.20官方制剂中的附加物质、赋形剂、组分（Added Substances, Excipients, and Ingredients in Official Products）. 135.30 性状和溶解性（Description and Solubility）. 145.40 鉴定试验（Identification Test）. 145.50 含量分析（Assay）. 155.50.10 效价单位（生物效价）(Units of Potency (Biological)) 155.60 杂质和外来物质（Impurities and Foreign Substances）. 155.60.10 USP和NF物品的其它杂质（Other Impurities in USP and NF Articles）155.60.20 USP和NF物品中的残留溶剂（Residual Solvents in USP and NF Articles）165.70性能检测（Performance Tests）. 165.80 USP标准品（Residual Solvents in USP and NF Articles）. 166. 检验规范和分析方法（Testing practices and procedures）166.10 安全的实验室规范（Safe Laboratory Practices）. 166.20 自动化程序（Automated Procedures）. 166.30 可选择的和谐的方法与程序（Alternative and Harmonized Methods and Procedures）166.40 干燥的、无水的、灼烧的、无溶剂的（Dried, Anhydrous, Ignited, or Solvent-Free Basis）176.40.10 灼烧至恒重（Ignite To Constant Weight）. 176.40.20 干燥至恒重（Dried T o Constant Weight）. 176.50 溶液的制备（Preparation of Solutions）. 186.50.10 过滤（Filtration）. 186.50.20 溶液（Solutions）. 186.60 完成一个实验所需多少单位（Units Necessary to Complete a Test）. 186.60.10 片剂（Tablets）. 186.60.20 胶囊（Capsules）. 196.70 试剂（Reagents）. 196.80 设备（Equipment）. 196.80.10 测量仪器（Apparatus for Measurement）. 196.80.20 仪器设备（Instrumental Apparatus）. 197. 测试结果（Test Results）. 207.10 质量要求的解释 (Interpretation of Requirements) 207.10.10 滴定程序中的等效表述 (Equivalence Statements in Titrimetric Procedures) 207.20 修约原则 (Rounding Rules) 208. 术语和定义 (Terms and Definitions) 218.10 缩写 (Abbreviations) 218.20 大约 (About) 218.30 乙醇含量 (Alcohol Content) 218.40 原子量(Atomic Weights) 228.50 空白试验(Blank Determinations) 228.60伴随(Concomitantly) 228.70 干燥器(Desiccator) 228.80 对数（Logarithms）. 228.90 微生物菌株(Microbial Strain) 228.100 可忽略的（Negligible）. 228.110 NLT/NMT 228.120 气味(Odor) 228.130 百分比(Percent) 228.140 百分比浓度(Percentage Concentrations) 238.150 压力(Pressure) 238.160 反应时间(Reaction Time) 238.170 比重(Specific Gravity) 238.180 温度(Temperatures) 238.190 时间(Time) 238.200 转移（Transfer）. 238.210 真空（Vacuum）. 238.220 真空干燥器（Vacuum Desiccator）. 238.230 水（Water）. 248.230.10 水作为官方制剂中的组分（Water as an Ingredient in an Official Product）24 8.230.20 水用于官方原料药的生产（Water in the Manufacture of Official Substances）24 8.230.30 药典实验操作用水（Water in a Compendial Procedure）. 248.240 称量和测量（Weights and Measures）. 249. 开处方和配药（Prescribing and Dispending）. 259.10 公制单位的使用（Use of Metric Units）. 259.20 体积的改变（Changes in Volume）. 2510. 保存、包装、储存、贴签（preservation，packaging，storage and labeling）2510.10 在非特定条件下储存（Storage Under Nonspecific Conditions）. 2510.20 包装容器（Containers）. 2510.20.10显窃启包装（Tamper-Evident Packaging）. 2610.20.20 避光容器（Light-Resistant Container）. 2610.20.30密闭良好的容器（Well-Closed Container）. 2610.20.40密封的容器（Tight Container）. 2610.20.50严封的容器（Hermetic Container）. 2710.20.60单元包装（Single-Unit Container）. 2710.20.70单剂量包装（Single-Dose Container）. 2710.20.80单元剂量容器（Unit-Dose Container）. 2710.20.90单元使用的容器（Unit-of-Use Container）. 2710.20.100多单元容器（Multiple-Unit Container）. 2710.20.110多剂量容器（Multiple-Dose Container）. 2710.20.120毒物保护包装法案（Requirements under the Poison Prevention Packaging Act (PPPA)） 2710.30 储存温度和湿度（Storage Temperature and Humidity）. 2810.30.10 冷冻（Freezer）. 2810.30.20冷处（Cold）. 2810.30.30 凉处（Cool）. 2810.30.40 可控的凉爽温度（controlled cold temperature）. 2810.30.50 室温（room temperature）. 2910.30.60 可控的室温（Controlled Room Temperature）. 2910.30.70 温暖（warm）. 2910.30.80 过热（Excessive Heat）. 2910.30.90 防冻（Protection From Freezing）. 2910.30.100 干燥处（Dry Place）. 2910.40 标签（Labeling）. 2910.40.10每个剂量单元中组分的量（Amount of Ingredient Per Dosage Unit）3010.40.20 首位和末位零的使用（Use of Leading and Terminal Zeros）. 3010.40.30药品中盐的标示（Labeling of Salts of Drugs）. 3010.40.40含维生素产品的标示（Labeling Vitamin-Containing Products）. 3010.40.50含植物药材的产品的标示（Labeling Botanical-Containing Products）3110.40.60非肠道和局部制剂的标示（Labeling Parenteral And Topical Preparations）3110.40.70电解液的标示（Labeling Electrolytes）. 3110.40.80乙醇的标示（Labeling Alcohol）. 3110.40.90特殊的胶囊和片剂（Special Capsules and Tablets）. 3110.40.100有效期和失效期（expiration date and beyond-use date）. 3110.50 USP-NF药典正文中关于包装和储存的指南（Guidelines for Packaging and Storage State ments in USP–NF Monographs）. 32General Notices and Requirements(凡例和要求)Change to read:凡例部分为药典的解释和应用提出了基本的假定、定义、默认条件。
1目的1.1 通过对所采购药用辅料甘油各项质量标准的检测，确定其自身安全性。
1.2 通过对所采购药用辅料甘油各项质量标准的检测，确定是否影响产品生产、产品质量、产品的安全性和有效性。
2 适用范围适用于本公司用于生产液体棉签所采购的药用辅料甘油。
3 责任者：质量部经理化验员4引用标准：中华人民共和国药典 2010年版二部美国药典 USP5包装与贮存要求：保存在密闭容器6 操作6.1鉴别（符合红外吸收197 F和6.1.2的鉴别反应）6.1.1 所需仪器、试剂：气象色谱仪、USP二甘醇（对照品）、USP乙二醇（对照品）、USP 甘油（对照品）、甲醇、氦气6.1.26.1.2.1 标准储存溶液1:准确称量50mg的USP二甘醇（对照品），用甲醇溶解并稀释到100ml容量瓶中。
6.1.2.2 标准储存溶液2:准确称量50mg的USP乙二醇（对照品），用甲醇溶解并稀释到100ml容量瓶中。
6.1.2.3标准储存溶液3:准确称量50mg的USP甘油（对照品），用甲醇溶解并稀释到100ml 容量瓶中。
6.1.2.4解决方案---把每种储存溶液中各取5毫升，放入100毫升的容量瓶中，用甲醇溶解并稀释到100ml容量瓶中。
6.1.2.5测试溶液---取5g甘油，加入到100毫升的容量瓶中，用甲醇溶解并稀释到100ml 容量瓶中。
6.1.2.6色谱系统(见色谱621)--- 在气相色谱仪配备一个火焰离子化检测器，一个0.53毫米×30 m熔融石英分析柱涂有3.0 -µm G43固定相。
注射口温度保持在220和检测器温度保持在250。
载气是氦气，流率约为每分钟4.5毫升。
分流比相当于10：1。
色谱程序,如下所示：最初,柱温是在100，保持4分钟，然后温度以50的比率增加到120，保持10分钟。
然后温度再以50的比率增加到220，保持6分钟。
色谱仪拆分溶液,并记录峰值响应和保留时间。
他相对保留时间约为乙二醇0.3 ，二甘醇0.8，甘油1.0；复制注射的二甘醇的相对标准偏差为不会超过10%。
美国药典（USP）有机溶剂标准购买search制药参考标准品中文版 | English公司简介新闻动态诚聘英才联系我们Restek GCRestek LCVarian GC资料产品类别现货速递(不断更新中)三氯乙烯DMSO0.4mg/mL MNK137016m-二甲苯DMSO 6.51mg/mL MNK137018o-二甲苯DMSO0.97mg/mL MNK137019p-二甲苯DMSO 1.52mg/mL MNK137020 DMSO = 二甲亚砜这些混合物反映了2008年7月1日生效的USP30/NF25中做出的改变。
残留溶剂 - 等级 1 (5种成分)苯 10mg/mL1,1-二氯乙烯 40四氯化碳 201,1,1-三氯乙烷 501,2-二氯乙烷 25溶剂为二甲亚砜, 1mL/安瓿货号 36279 (单件)残留溶剂等级 2 - 混合物 A (15种成分)乙腈 2.05mg/mL甲基环己烷 5.90氯苯 1.80二氯甲烷 3.00环己烷 19.40四氢呋喃 3.45顺-1,2-二氯乙烯 4.70甲苯 4.45反-1,2-二氯乙烯4.70m-二甲苯6.51 1,4-二氧己环1.90o-二甲苯0.98乙基苯1.84p-二甲苯 1.52甲醇 15.00溶剂为二甲亚砜, 1mL/安瓿货号 36271 (单件)残留溶剂等级 2 - 混合物 B (8种成分)氯仿60μg/mL硝基甲烷 501,2-二甲氧基乙烷 100嘧啶200n-己烷 (C6) 290萘满1002-己酮 50三氯乙烯 80溶剂为二甲亚砜, 1mL/安瓿货号 36280 (单件)残留溶剂等级 2 - 混合物 C (8种成分)2-乙二醇单乙醚800μg/mL2-甲氧基乙醇(甲基溶纤剂)乙烯乙二醇 3,100250甲酰胺 1,100N-甲基吡咯烷酮2,650N,N-二甲基乙酰胺 5,450环丁砜800N,N-二甲基甲酰胺 4,400溶剂为二甲亚砜, 1mL/安瓿货号 36273 (单件)第1级混合物反映了2000年1月1日生效的USP24/NF19与1995年1月1日到1999年12月31日之间有效的USP23/NF18之间的变化。
学报Journal of China Pharmaceutical University2022，53（3）：293-299293气相色谱法测定药用辅料聚西托醇1000中的残留杂质李浩宇1，2，唐宝强1，2，何东升1，2*，涂家生1，2**（1中国药科大学药学院药用辅料及仿创药物研发评价中心，南京210009；2国家药品监督管理局药物制剂及辅料研究与评价重点实验室，南京210009）摘要建立气相色谱法测定聚西托醇1000中残留的环氧乙烷、1，4-二氧六环、乙二醇、二甘醇和三甘醇等杂质，为聚西托醇1000生产质量控制提供参考。
采用DB-1色谱柱检测环氧乙烷和1，4-二氧六环，顶空进样，进样口温度150℃，检测器温度250℃，顶空平衡温度70℃，平衡时间45min。
采用VF-17MS色谱柱检测乙二醇、二甘醇和三甘醇，液体进样，进样口温度270℃，检测器温度290℃。
实验结果显示，环氧乙烷和1，4-二氧六环在各加样量范围内线性良好（r>0.999），精密度RSD小于8.0%，平均回收率分别为90.6%和101.2%；乙二醇、二甘醇和三甘醇在3~60μg/mL内线性关系良好（r> 0.999），精密度RSD小于3.0%，回收率均在96%~103%。
本研究所建立的方法具有良好的专属性、线性、精密度和回收率，能够有效检测聚西托醇1000中多组分极微量杂质。
关键词聚西托醇1000；杂质；气相色谱法；环氧乙烷；1,4-二氧六环；乙二醇；二甘醇；三甘醇中图分类号R944；R917文献标志码A文章编号1000-5048（2022）03-0293-07doi：10.11665/j.issn.1000-5048.20220306引用本文李浩宇，唐宝强，何东升，等.气相色谱法测定药用辅料聚西托醇1000中的残留杂质［J］.中国药科大学学报，2022，53（3）：293–299.Cite this article as：LI Haoyu，TANG Baoqiang，HE Dongsheng，et al.Determination of residual impurities in pharmaceutical excipient ceto⁃macrogol1000by gas chromatography［J］.J China Pharm Univ，2022，53（3）：293–299.Determination of residual impurities in pharmaceutical excipient cetomacro⁃gol1000by gas chromatographyLI Haoyu1,2,TANG Baoqiang1,2,HE Dongsheng1,2*,TU Jiasheng1,2**1Center for Research Development and Evaluation of Pharmaceutical Excipients and Generic Drugs,School of Pharmacy,China Pharmaceutical University,Nanjing210009;2National Medical Products Administration(NMPA)Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients,Nanjing210009,ChinaAbstract For the quality control of cetomacrogol1000,a gas chromatographic method for the determination of residual impurities in cetomacrogol1000,such as ethylene oxide,1,4-dioxane,ethylene glycol,diethylene glycol and triethylene glycol,was established and validated.The DB-1column with headspace injection was used to detect ethylene oxide and1,4-dioxane with the inlet temperature of150°C,the FID temperature of250°C,the headspace equilibration temperature of70°C and the equilibration time of45min.The VF-17MS column with liquid injection was used to detect ethylene glycol,diethylene glycol and triethylene glycol with the inlet tempera⁃ture of270°C,and the FID temperature of290°C.The results showed that ethylene oxide and1,4-dioxane havea good linearity within their specified addition amount ranges(r>0.999),with the RSD of precision of below8.0%and the average recovery rates of90.6%and101.2%;and that ethylene glycol,diethylene glycol and triethylene glycol also have a good linearity between3‒60μg/mL(r>0.999),with the RSD of precision of below3.0%,and the recovery rates of96%~103%.The method established in this study has good specificity,收稿日期2022-01-06通信作者*Tel：025-********E-mail：dongshenghe@**Tel：025-********E-mail：jiashengtu@基金项目国家“重大新药创制”科技重大专项资助项目（No.2017ZX09101001-006-002）；国家药典委员会药品标准制修订研究课题2020Y047学报Journal of China Pharmaceutical University2022，53（3）：293-299第53卷linearity,precision and recovery rate,which can effectively detect the multi-component and trace impurities. Key words cetomacrogol1000;impurity;gas chromatography;ethylene oxide;1,4-dioxane;ethylene glycol;diethylene glycol;triethylene glycolThis study was supported by China National Key Hi-Tech Innovation Project for the R&D of Novel Drugs(No.2017ZX09101001-006-002)and the Drug Standard Establishment and Revision Project of Chinese Pharmacopoeia Commission(No.2020Y047)聚西托醇1000（又称聚乙二醇十六烷基醚），是一种常见的药用辅料，化学式为C m H2m+1（OCH2CH2）n OH（m=16，n~20），本品由十六醇与一定数量的环氧乙烷通过缩合反应制得，产品中聚乙二醇的重复单元在2~20之间，当n=20时即为聚西托醇1000（商品名Brij-58）［1］。
乙二醇和二甘醇的限制要求概述说明1. 引言1.1 概述本文旨在探讨乙二醇和二甘醇的限制要求。
乙二醇和二甘醇是两种常见的有机化合物，广泛应用于工业生产和消费品制造过程中。
然而，由于它们的特性和潜在风险，限制要求成为确保安全使用的必要举措。
1.2 文章结构本文将分为五个部分进行论述。
引言部分旨在提出本文的研究目标，并介绍文章结构。
其后，会依次探讨乙二醇和二甘醇的限制要求，包括定义和特性、安全性评估要点以及使用限制要求。
接下来，我们将比较乙二醇和二甘醇的限制要求，分析其物理化学性质、生产与用途差异对限制要求的影响，并对国际标准和法规进行比较研究。
最后，我们将给出本文的结论并展望未来发展趋势。
1.3 目的本文旨在总结乙二醇和二甘醇的限制要求，并比较它们之间存在的差异。
通过对两种化合物的特性和潜在风险进行评估，我们可以更好地了解如何安全使用乙二醇和二甘醇，并为相关行业提供指导。
同时，通过比较国际标准和法规，我们可以揭示不同地区对乙二醇和二甘醇限制要求的差异，为国内外企业合规运营提供参考依据。
通过本文的研究，我们希望能够促进有机化合物的可持续发展，并为相关领域的决策制定者提供科学依据。
2. 乙二醇的限制要求2.1 定义和特性乙二醇（ethylene glycol），也被称为1,2-乙二醇或MEG，是一种无色、无臭的液体。
它具有良好的溶解性和挥发性，并易于与许多有机化合物混合。
乙二醇广泛应用于化工、塑料、纺织品、医药等领域。
2.2 安全性评估要点为了确保乙二醇的安全使用，制定了以下安全性评估要点：首先，需要对乙二醇进行毒理学评估。
这包括确定其急性毒性、亚慢性和慢性毒性以及过敏原性等特征。
其次，需要进行燃烧和爆炸特性评估。
这涵盖了乙二醇与其他物质（例如氧气）的反应和可燃物品列表。
此外，还需对乙二醇进行生态毒理学评估，以确定对环境的潜在危害。
最后，在安全评估中还需要考虑到人们可能会通过空气吸入、皮肤接触或误食等途径暴露于乙二醇的风险。
GlycerinC 3H 8O 3 92.101,2,3-Propanetriol.Glycerol [56-81-5].» Glycerin contains not less than 99.0 percent and not more than 101.0 percent of C 3H 8O 3, calculated on the anhydrous basis. The amount of any individual impurity, excluding diethylene glycol and ethylene glycol, if detected, meets the requirements under Other Impurities (NMT 0.1%) and the amount of total impurities, including diethylene glycol and ethylene glycol, is NMT 1.0%. Packaging and storage— Preserve in tight containers.USP Reference standards 11— USP Diethylene Glycol RS . USP Ethylene Glycol RS . USP Glycerin RS .Color— Its color, when viewed downward against a white surface in a 50-mL color-comparison tube, is not darker than the color of a standard made by diluting 0.40 mL of ferric chloride CS with water to 50 mL and similarly viewed in a color-comparison tube of approximately the same diameter and color as that containing the Glycerin.Identification— [NOTE—Compliance is determined by meeting the requirements for both Identification A and B .]A: Infrared Absorption 197F .B: Standard stock solution 1—Transfer 50 mg of USP Diethylene Glycol RS , accurately weighed, to a 100-mL volumetric flask, dilute with methanol to volume, and mix. Standard stock solution 2— Transfer 50 mg of USP Ethylene Glycol RS , accurately weighed, to a 100-mL volumetric flask, dilute with methanol to volume, and mix.Standard stock solution 3— Transfer 50 mg of USP Glycerin RS , accurately weighed, to a 100-mL volumetric flask, dilute with methanol to volume, and mix.Resolution solution— Transfer 5.0 mL each of Standard stock solution 1, Standard stock solution 2, and Standard stock solution 3, to a 100-mL volumetric flask, dilute withmethanol to volume, and mix.Test solution— Transfer about 5 g of Glycerin to a 100-mL volumetric flask, dilute with methanol to volume, and mix.Chromatographic system (see Chromatography 621)— The gas chromatograph is equipped with a flame-ionization detector, a 0.53-mm × 30-m fused-silica analytical column coated with 3.0-µm G43 stationary phase. The injection port temperature is maintained at 220 and the detector temperature is maintained at 250. The carrier gas is helium with a flow rate of about 4.5 mL per minute. The split flow ratio is about 10:1. The chromatograph is programmed as follows: Initially, the column temperature is equilibratedat 100 for 4 minutes, then increased at a rate of 50 per minute to 120, and is maintained at 120 for 10 minutes. It is then increased at a rate of 50 per minute to 220, and is maintained at 220 for 6 minutes. Chromatograph the Resolution solution, and record the peak responses and retention times as directed for Procedure: the relative retention times are about 0.3 for ethylene glycol, 0.8 for diethylene glycol, and 1.0 for glycerin; and the relative standard deviation for replicate injections for the diethylene glycol is not more than 10%.Procedure— Separately inject equal volumes (about 1 µL) of the Resolution solution and the Test solution into the chromatograph, and record the chromatograms. If a peak at the relative retention time for the diethylene glycol or ethylene glycol is present in the Test solution, the peak must be identifed and quantified as directed in the test for Diethylene glycol and ethylene glycol impurities.Specific gravity 841: not less than 1.249.Residue on ignition 281—Heat 50 g in an open, shallow 100-mL porcelain dish until it ignites, and allow it to burn without further application of heat in a place free from drafts. Cool, moisten the residue with 0.5 mL of sulfuric acid, and ignite to constant weight: the weight of the residue does not exceed 5 mg (0.01%).Water, Method I 921: not more than 5.0%.Chloride 221—A 7.0-g portion shows no more chloride than corresponds to 0.10 mL of 0.020 N hydrochloric acid (0.001%).Sulfate 221—A 10-g portion shows no more sulfate than corresponds to 0.20 mL of 0.020 N sulfuric acid (about 0.002%).Heavy metals 231—Mix 4.0 g with 2 mL of 0.1 N hydrochloric acid, and dilute with water to 25 mL: the limit is 5 µg per g.Limit of chlorinated compounds— Accurately weigh 5 g of Glycerin into a dry, round-bottom, 100-mL flask, add 15 mL of morpholine, and connect the flask by a ground joint to a reflux condenser. Reflux gently for 3 hours. Rinse the condenser with 10 mL of water,receiving the washing in the flask, and cautiously acidify with nitric acid. Transfer the solution to a suitable comparison tube, add 0.50 mL of silver nitrate TS, dilute with water to 50.0 mL, and mix: the turbidity is not greater than that of a blank to which 0.20 mL of 0.020 N hydrochloric acid has been added, the refluxing being omitted (0.003% of Cl).Fatty acids and esters— Mix 50 g of Glycerin with 50 mL of freshly boiled water and 5 mL of 0.5 N sodium hydroxide VS, boil the mixture for 5 minutes, cool, add phenolphthalein TS, and titrate the excess alkali with 0.5 N hydrochloric acid VS. Performa blank determination (see Residual Titrations under Titrimetry 541): not more than 1 mL of 0.5 N sodium hydroxide is consumed.Diethylene glycol and ethylene glycol impurities—Internal standard solution— Transfer 100 mg of 2,2,2-trichloroethanol (internal standard), accurately weighed, to a 100-mL volumetric flask, dilute with methanol to volume, and mix.Standard stock solution 1— Transfer 50 mg of USP Diethylene Glycol RS, accurately weighed, to a 100-mL volumetric flask, dilute with methanol to volume, and mix.Standard stock solution 2— Transfer 50 mg of USP Ethylene Glycol RS, accurately weighed, to a 100-mL volumetric flask, dilute with methanol to volume, and mix.Standard stock solution 3— Transfer 50 mg of USP Glycerin RS, accurately weighed, to a 100-mL volumetric flask, dilute with methanol to volume, and mix.Standard solution— Transfer 5.0 mL each of Standard stock solution 1, Standard stock solution 2, and the Internal standard solution to a 100-mL volumetric flask, and dilute with methanol to volume, and mix.Resolution solution— Transfer 500 mg of USP Glycerin RS to a 10-mL volumetric flask, add 0.5 mL each of Standard stock solution 1 and Standard stock solution 2, dilute with methanol to volume, and mix.Test solution— Transfer about 5 g of Glycerin to a 100-mL volumetric flask, add 5.0 mL of Internal standard solution, dilute with methanol to volume, and mix.Chromatographic system (see Chromatography 621)— The gas chromatograph is equipped with a flame-ionization detector, a 0.53-mm × 30-m fused-silica analytical column coated with 3.0-µm G43 stationary phase. The injection port temperature is maintained at 220 and the detector temperature is maintained at 250. The carrier gas is helium, flowing at a rate of about 4.5 mL per minute. The split flow ratio is about 10:1. The chromatograph is programmed as follows. Initially, the column temperature is equilibratedat 100 for 4 minutes, then increased at a rate of 50 per minute to 120, and is maintained at 120 for 10 minutes then increased at a rate of 50 per minute to 220, andis maintained at 220for 6 minutes. Chromatograph the Standard solution, and record thepeak response ratio and retention times as directed for Procedure: the relative retention times are about 0.3 for ethylene glycol, 0.8 for diethylene glycol, and 1.0 for glycerin; the relative standard deviation for replicate injections for the diethylene glycol is not more than 10%; and the limit of quantitation of diethylene glycol and ethylene glycol is not more than 0.025%.Procedure— Separately inject equal volumes (about 1 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the ethylene glycol and diethylene glycol peaks. Calculate the percentage of diethylene glycol and ethylene glycol in the portion of Glycerin taken by the formula:100(CS / CU)(RU/ RS)in which CSis the concentration, in mg per mL, of diethylene glycol (or ethylene glycol) inthe Standard solution; CUis the concentration, in mg per mL, of Glycerin in the Testsolution; and RU and RSare the peak response ratios for diethylene glycol (or ethyleneglycol) to the internal standard peak obtained from the Test solution and the Standard solution: NMT the limit of quantitation for each, is found (0.025%).Assay—Sodium periodate solution— Dissolve 60 g of sodium metaperiodate in sufficient water containing 120 mL of 0.1 N sulfuric acid to make 1000 mL. Do not heat to dissolve the periodate. If the solution is not clear, pass through a sintered-glass filter. Store the solution in a glass-stoppered, light-resistant container. Test the suitability of this solution as follows. Pipet 10 mL into a 250-mL volumetric flask, dilute with water to volume, and mix. To about 550 mg of Glycerin dissolved in 50 mL of water add 50 mL of the diluted periodate solution with a pipet. For a blank, pipet 50 mL of the solution into a flask containing 50 mL of water. Allow the solutions to stand for 30 minutes, then to each add 5 mL of hydrochloric acid and 10 mL of potassium iodide TS, and rotate to mix. Allow to stand for 5 minutes, add 100 mL of water, and titrate with 0.1 N sodium thiosulfate, shaking continuously and adding 3 mL of starch TS as the endpoint is approached. The ratio of the volume of 0.1 N sodium thiosulfate required for the glycerin–periodate mixture to that required for the blank should be between 0.750 and 0.765.Procedure— Transfer about 400 mg of Glycerin, accurately weighed, to a 600-mL beaker, dilute with 50 mL of water, add bromothymol blue TS, and acidify with 0.2 N sulfuric acid to a definite green or greenish yellow color. Neutralize with 0.05 N sodium hydroxide to a definite blue endpoint, free from green color. Prepare a blank containing 50 mL of water, and neutralize in the same manner. Pipet 50 mL of the Sodium periodate solution into each beaker, mix by swirling gently, cover with a watch glass, and allow to stand for 30minutes at room temperature (not exceeding 35) in the dark or in subdued light. Add 10 mL of a mixture of equal volumes of ethylene glycol and water, and allow to stand for 20 minutes. Dilute each solution with water to about 300 mL, and titrate with 0.1 N sodiumhydroxide VS to a pH of 8.1 ± 0.1 for the specimen under assay and 6.5 ± 0.1 for the blank, using a pH meter. Each mL of 0.1 N sodium hydroxide, after correction for the blank, is equivalent to 9.210 mg of C 3H 8O 3.Auxiliary Information— Please check for your question in the FAQs before contacting USP.USP32–NF27 Page 2513Pharmacopeial Forum : Volume No. 28(4) Page 1245Chromatographic Column— GLYCERINChromatographic columns text is not derived from, and not part of, USP 32 or NF 27. Topic/Question Contact Expert Committee Monograph Kevin T. Moore, Ph.D.Scientist1-301-816-8369(EM105) Excipient Monographs 1Reference StandardsLili Wang, Technical ServicesScientist1-301-816-8129RSTech@。
