滴定液管理规程

1、 职位 Position 姓名/部门 签名/日期Signature/Date起草 Prepared ByQC 检验员卓毓聂曦光/质量控制部QC Analyst 审核 Reviewed ByQC 经理QC Manager 谢圣坤/质量控制部审核 Reviewed ByQA 经理QA Manager 全海军/质量保证一部批准 Approved By质量受权人Qualified Person 冯吉/厂区质量负责人生效日期 Effective Date：制作备份：4 份；分发部门：质量保证一部、质量控制部办公室、质量控制部理化岗位、车间化验岗位Prepared Copies:4 Copies; Dis

2、tributed To:Quality Assurance Department 1, Office of Quality Control Department, Physicochemical Testing Post of Quality Control Department, Intermediate Control Department1、目的、目的 PURPOSE建立滴定液管理规程，使滴定液配制、标定、使用规范化。Establish the management regulation for volumetric solutions to regulate the preparati

3、on, standardization and use of volumetric solutions.2、适用范围、适用范围 SCOPE 滴定液 Volumetric Solutions3、依据及参考文件、依据及参考文件 REFERENCES3.1中华人民共和国国家标准GB/T 601200288GB/T 6012002 88 of National Standards of Peoples Republic of China3.2中国药品检验标准操作规范2010 年版Standard Operation Norm of Chinas Drug Inspection, 20103.3中华人民

4、共和国药典2010 年版附录 XVF Appendix XVF of Pharmacopoeia of Peoples Republic of China, 20103.4 SOP-QC-020溶液配制标准管理规程 “SOP for Management of Solution Preparation”3.5 SOP-QC-001QC 实验室管理规程 “SOP for QC Laboratory Management”3.6中华人民共和国药典2010 年版 （第一增补本）First Supplemental Amended Volume of Pharmacopoeia of Peoples

5、Republic of China, 20104、职责、职责 RESPONSIBILITIES4.1 滴定液管理员 Volumetric Solutions Administrator：4.1.1 根据使用量及库存量，及时配制、标定滴定液。Prepare and standardize volumetric solutions according to usage and inventory timely;4.1.2 负责过有效期滴定液销毁。Responsible for destruction of invalid volumetric solutions 4.2 QC 检验员 QC Ana

6、lyst：按照此操作规程执行。Implement this SOP4.3 QC 经理 QC Manager：保证检验员按照此文件的要求执行。Assure the analyst implement this SOP5、内容内容 CONTENT5.1 简述简述 Resume5.1.1 滴定液系指在容量分析中用于滴定被测物质含量的标准溶液，具有准确的浓度(取 4 位有效数字)。Volumetric solutions are the standard solutions with precise concentration (with 4 significant digits) which are

7、 used to titrate measured matter content in capacity analysis.5.1.2 滴定液的浓度以“mol/L”表示，其基本单位应根据药典规定。The concentration of the titrate is expressed by mol/L, its basic unit should be based on the regulations of Chinese Pharmacopoeia. 5.1.3 滴定液的浓度值以其名义值之比，称为“F”值，常用于容量分析的计算。The F value often used in the c

8、alculation of capacity analysis is defined as the ratio of the concentration of volumetric solutions and its nominal value.5.2 仪器与用具仪器与用具 Instruments and appliances5.2.1 分析天平 Analytical balance 其分度值应为 0.1mg 或小于 0.1mg：毫克组砝码需经校正，并列有校正表备用。Its value of a scale division should be 0.1 mg or less than 0.1

9、mg; weights of mg group require correction, and list the correction table for a rainy day. 5.2.2 10ml25ml 和 50ml 滴定管 10ml, 25ml, 50ml burettes 应附有该滴定管的校正曲线或校正值。Standardization curve or standardization value should be attached to each of them.5.2.3 250ml 和 1000ml 量瓶 250ml 和 1000ml volumetric flask 应附

10、合国家 A 级标准，或有校正值。National A level standard or standardization value should be attached to each of them.5.3 试药与试液试药与试液 Reagents and Solutions5.3.1 均应按照中国药典二部附录 XVF “滴定液”项下的规定取用(见附件一)。Taken according to the regulations under volumetric solutions item of Appendix XVF of Chinese Pharmacopoeia5.3.2 基准试剂应有

11、专人负责保管与领用。Appoint responsible persons for keeping and requisition of benchmark reagents.5.4 配制配制 Preparation滴定液的配制方法有间接配制法与直接配制法两种，应根据规定选用，并应遵循下列有关规定。Indirect method and direct method are two kinds of the preparation methods of volumetric solutions, which should be chosen by regulations, and the fol

12、lowing relevant regulations should be followed.5.4.1 所用溶剂“水”，系指蒸馏水或去离子水，在未注明有其他要求时，应符合中国药典 “纯化水”项下规定。The solvent water, including distilled water or deionized water, should conform to regulations under Purified water item of Chinese Pharmacopoeia, without any other stated requirements.5.4.2 采用间接配制法时

13、，溶质与溶剂的取用量均应定量称取或量取，并使制成后滴定液的浓度值应为其名义值的 0.951.05：如在标定中发现其浓度值超出其名义值的0.951.05 范围时，应加入适量的溶质或溶剂予调整。当配制量大于 1000ml 时，其溶质与溶剂的取用量均应按比例增加。When indirect method is used for preparation, the amount of solute and solvent should be weighed or measured according to ration, the F value，ratio of the concentration of

14、 volumetric solutions and its nominal value ，should be between 0.95 and 1.05; if the ratio was out of the range, add optimum amount of solutes and solvents for the adjustment. When the amount of preparation is more than 1000ml, the amount of solute and solvent should both increase in proportion.5.4.

15、3 采用直接配置法时，其溶液应采用“基准试剂”，并按规定条件干燥至恒重后称取，取用量应为精密称定（精确至 45 位有效数字） ，置 1000ml 量瓶中，加溶剂溶解并稀释至刻度，摇匀。When direct method is used for preparation, the solution should be prepared with primary standard, and weigh the reagents accurately after drying to constant weight in prescribed conditions, (with 45 signific

16、ant digits), put into 1000ml volumetric flask, add solvent to dissolve and dilute to scale, shake well. 5.4.4 配制过程中应有复核人，由配制人填写溶液配制记录和溶液标签并由配制人、复核人签名以示负责，并将溶液标签粘贴在溶液贮瓶外。滴定液编号规则按溶液配制标准管理规程规定执行。外购滴定液的编号为该批滴定液的批号。There should be checkers in the process of preparation, and the preparation personnel fill

17、 the prepared solution records and the solution label and sign by prepare personnel and checkers to show responsibility, Stick the solution label on solution storage bottle. Numbering rules are executed according to the regulations of SOP for Management of Solution Preparation. Numbers of outsourcin

18、g volumetric solutions are the batch numbers. 5.4.5 配制浓度等于或低于 0.02mol/L 的滴定液时，除另有规定外，应于临用前精密量取浓度等于或大于 0.1mol/L 的滴定液适量，加新沸过的冷水或规定的溶剂定量稀释制成。When the prepared concentration of the volumetric solution is equal to or lower than 0.02 mol/L, measure optimum amount of the volumetric solution whose concentra

19、tion is equal to or higher than 0.1 mol/L precisely before use, prepare by adding the cold fresh boiling water or specified solvent to dilute according to ration, unless otherwise specified.5.4.6 配制成的滴定液必须澄清，必要时可滤过，并按药典中各滴定液项下的（贮藏）条件贮存，经下述标定其浓度后方可使用。Prepared volumetric solutions must be clear, filtr

20、ation can be done when necessary, and stored according to (storage) conditions under each volumetric solutions item of Pharmacopoeia, can use till its concentration was standardized through the following standardization.5.5 标定标定 Standardization5.5.1“标定”系指根据规定的方法，用基准物质或已标定的滴定液准确测定滴定液浓度（mol/L）的操作过程，应严

21、格遵照药典中该滴定液项下的方法进行标定，并应遵循下列有关规定。Standardization is the operating process that determinate the concentration of volumetric solution (mol/L) accurately with benchmark reagents or standardized volumetric solutions in procedural manner. The volumetric solution should be calibrated in accordance with mann

22、er under each relevant volumetric solution items of Pharmacopoeia and should follow the following relevant regulations.5.5.2 工作中所用的分析天平及其砝码、滴定管、量瓶和移液管等，均应经过检定合格；其示值误差大于 0.05时，应在计算中应采用校正值，予以补偿。Analytical balance and its weights, burettes, volumetric flasks and transfer pipettes and so on which used d

23、uring work should be all qualified through verification. Corrected value should be used in the standardization for compensation, when the corrected value is more than 0.05%.5.5.3 标定工作宜在室温（1030）下进行，并应在记录中注明标定时的室内温度。The appropriate room temperature for standardization activities is 1030,and the indoor

24、 temperature should be noted in the record.5.5.4 所用基准物质应采用“基准试剂”，取用时应先用玛瑙乳钵研细，并按规定条件干燥，置干燥器中放冷至室温后，精密称取（精确至 45 位数） ，有引湿性的基准物质应采用“减量法”进行称重。如系以另一已标定的滴定液作为标准溶液，通过“比较”进行标定，则该另一已标定的滴定液的取用应为精密量取（精确至 0.01ml） ，用量除另有规定外应等于或大于 20ml，其浓度应按药典规定准确标定。Primary standard should be used. Grind to fine powder with morta

25、r before used, dry under specific conditions, cool to room temperature in the dryer. Weigh precisely (accurate to 45 significant digits), with hygroscopic property by subtraction method. If another volumetric solution which have been standardized was used as standard solution, calibrate by compare,

26、so the amount of another volumetric solutions should be measured precisely (accurate to 0.01ml) and be equal to or more than 20ml, the concentration should be calibrated exactly according to Pharmacopoeia, unless otherwise specified.5.5.5 根据滴定液的消耗量选用适宜容量的滴定管，滴定管应洁净，玻璃活塞应密合、旋转自如，盛装滴定液前，应先用少量的滴定液淋洗 3

27、次，盛装滴定液后，宜用小烧杯覆盖管口。Burettes with appropriate volume tube are selected according to consumption of volumetric solutions. The burettes should be clean, and the glass piston should be closed and rotate freely. Rinse burette three times with a small quantity of volumetric solutions before it contains vo

28、lumetric solutions, its appropriate to cover mouth of tube with a small beaker after volumetric solutions have been held.5.5.6 标定中，滴定液宜从滴定管的起始刻度开始，滴定液的消耗量，除另有特殊规定外，应大于 20ml，读数应估计到 0.01ml。Volumetric solutions should begin from starting graduation of scale of the burette in the standardization; the co

29、nsumption of volumetric solutions should more than 20ml and the reading by estimating the nearest 0.01ml, unless otherwise specified.5.5.7 标定中的空白试验，系指在不加供试品或以等量溶剂替代供试液的情况下，按同法操作和滴定所得结果。Blank assay in the standardization is the result by operating and titrating under conditions of adding no test samp

30、le or using the same amount of solvent as substitutes for test sample solution in the same way.5.5.8 标定工作应由初标定者（一般为配制者）和复标者在相同条件下各作平行试验 3份，各项原始数据经校正后，根据计算公式分别进行计算，3 份平行试验结果的相对平均偏差，除另有规定外，不得大于 0.1，初标平均值和复标平均值相对偏差也不得大于 0.1%，标定结果按初、复标的平均值计算，取 4 位有效位数字。Operation of calibration should be triplicate paral

31、lel experiments and done by original standardizing person （most commonly the prepared person ）and reviewing standardizing personnel respectively in the same conditions, calculate every original data according to calculation formula respectively after correction, relative deviations of triplicate par

32、allel experiments cant be greater than 0.1, average value of original standardizations and average value of reviewing standardizations neither, result of standardizations calculate in average value of original and reviewing standardization take four significant digits, unless otherwise specified.5.5

33、.9 初标与复标需要在同一天内完成。Original calibration and duplicate calibration need to be accomplished on the same day.5.5.10 直接法配制的滴定液，其浓度应按配制时基准物质的取用量（准确至 45 位数）与容量瓶的容量（加校正值）以及计算公式进行计算，最终取 4 位有效位数。Calculate the concentration of volumetric solutions prepared in direct method by the dosage of benchmark material (

34、accurate to 45 digits) and volume of volumetric flask with correction value and calculation formula, take four significant digits finally.5.5.11 临用前按稀释法配制浓度等于或低于 0.02mol/L 的滴定液，除另有规定外，其浓度可按原滴定液（浓度等于或大于 0.1mol/L）的标定浓度与取用量（加校正值） ，以及最终稀释成的容量（加校正值） ，计算而得。Volumetric solution prepared in dilution method w

35、hose concentration of is equal to or lower than 0.02mol/L, its concentration calculate in original standardizing concentration which is equal to and greater than 0.1mol/L and dosage with correction value and volume with correction value via final dilution before use.5.5.12 滴定液标定完成后，将滴定液标定记录交审核岗位审核，审

36、核无误后由滴定液标定人填写滴定液标签并粘贴在滴定液贮瓶醒目处。After the volumetric solution standardization has been accomplished, hand standardization records to review post to undertake examine and verify, fill volumetric solution label and stick it on the conspicuous place of volumetric solution container by standardizing pers

37、on after the standardization has been examined correct.5.6 贮藏与使用贮藏与使用 Storage and Use 5.6.1 滴定液在配制后应按药典规定的贮藏条件贮存，一般宜采用质量较好的具玻璃塞的玻璃瓶。放置在“待标定滴定液”处并上锁。Volumetric solutions should be stored according to the conditions provided by Pharmacopoeia after preparation, in suitable bottles with preferable quali

38、ty and glass stoppers generally. Be placed at volumetric solutions to be standardized location and locked. 5.6.2 滴定液经标定所得的浓度或其“F”值，除另有规定外，可在 3 个月应用，过期应重新标定。当标定与使用时的室温相差未超过 10时，除另有规定外，其浓度值可不加温度补正值，但当室温差超过 10时，应加温度补正值，或按本管理规程进行重新标定。Standardized concentration of volumetric solutions or F value can be u

39、sed in three months and should be recalibrated if expired, unless otherwise specified. The concentration value can be use without adjusted value of temperature, when there is not more than 10 differ between standardized temperature and room temperature when use, but the adjusted value should be cons

40、idered when the differ is more than 10, or recalibrated according to this SOP.5.6.3 取用滴定液时，一般应事先轻摇贮存有大量滴定液的容器，使与黏附于瓶壁的液滴混合均匀，而后分取略多于需用量的滴定液置于洁净干燥的具塞玻璃瓶中，用以直接转移至滴定管内，或用移液管量取，避免多次取用反复开启贮存滴定液的大容器，取出后的滴定液不得倒回贮存容器中，以避免污染。取用滴定液，使用人必须填写滴定液使用登记台帐 。The container hold plenty of volumetric solutions should be

41、swirled to make the liquid adhere wall of bottle mix uniformly in advance generally, and then place volumetric solutions into clean and dry glass stopper bottles whose amount little more than needed, transfer into burettes directly or measure by transfer pipettes, avoid measuring and opening the big

42、 container hold volumetric solutions repeatedly, the volumetric solutions which have been taken out cant pour back into storage container to guard against pollution. Once use volumetric solutions, the user must fill register account for use of volumetric solution.5.6.4 当滴定液出现浑浊或其他异常情况时，该滴定液应即弃去，不得再用

43、，检验员必须通知滴定液管理员，如不能及时销毁，必须放置在“待销毁”处并上锁。Volumetric solutions which occur turbines or other abnormal phenomena should be abandoned and never used again, checker must notice volumetric solutions administrator, and place volumetric solutions to be destroyed location and locked, if the solutions can not b

44、e destroyed timely.5.6.5 当滴定液出现过有效期，该滴定液应销毁，不得再用，如不能及时销毁，必须放置在“待销毁”处并上锁。Volumetric solutions which are expired should be destroyed and never used again, and the volumetric solutions which can not be destroyed timely should be placed at the location to be destroyed and locked,.5.7 检查检查 Inspection5.7.

45、1 检查频次：每 10 天检查一次现场使用的滴定液。Inspection frequency: inspect the VS which is used on-site every ten days. 5.7.2 检查内容：滴定液标签是否完好无损，字迹清晰可辨；滴定液是否变浑浊、有沉淀产生；是否近失效期。Inspection content: inspect to confirm whether the label is intact, whether the handwriting is clear, whether the VS becomes cloudy or generates pr

46、ecipitate, whether the VS is near its expiry date.5.7.3 近失效期溶液：从本次检查后至下次检查期间失效的滴定液。Solution which is near its expiry date: stand for the titrant which is expired during the inspection to the next inspection.5.8 销毁销毁 Destruction滴定液销毁必须按QC 实验室管理规程规定进行销毁。The destruction of volumetric solutions must pro

47、ceed according to the regulations of SOP for QC Laboratory Management.5.9 外购滴定液外购滴定液 Outsourcing Volumetric Solutions使用前应对其溶液进行标定,标定结果用于今后滴定液使用的真实浓度。Standardization of solutions should been operated before use. The result of standardization would be used as the true concentration of volumetric solut

48、ions in the future.6、附件、附件 ATTACHMENTS附表一：滴定液标定、配制、贮藏参考表 Attached Form 1：Reference Table of Standardization, Prepared and Reposition of Volumetric Solution 附件一：滴定液标定记录 SOP-QC-014/R01 Attachment 2：Volumetric Solution Standardization Record附件二：滴定液使用登记台帐 SOP-QC-014/R02 Attachment 3：Register Log for Use

49、 of Volumetric Solution附件三：滴定液标签 SOP-QC-014/R03 Attachment 4：Volumetric Solution Lable附件四：滴定液检查记录 SOP-QC-014/R04 Attachment 5：Volumetric Solution Inspection Record7、修订记录、修订记录 REVISION HISTORY文件编号Document Number修订内容Description of Revision生效日期Effective Date修订人Revised BySOP-QC-0015-V00按新版文件修订并细化操作及要求。A

50、ccording to update document revision and refinement operation and request.2009-06-01周烈翔SOP-QC-014-V00按新文件格式重新进行编号，统一格式，细化操作规程。Renumber according to the format of new document, unify the format, make detailed description for the operation procedure2011-07-18潘杰民SOP-QC-014-V01细化滴定液使用登记台帐 ，在使用用途上增加检品名称、

51、检品批号、检验项目的填写要求。Refine the Register Log for Use of Volumetric solution add filling requirement of quality inspection name、quality inspection batch number and inspection item. 2011-10-20周烈翔SOP-QC-014-V02按中国药典2010 年版第一增补本方法修订附表一中硫酸铈滴定液和碘滴定液的标定方法。Revise titrant calibration method of ceric sulfate and io

52、dine in Attached Form 1, according to Chinese pharmacopoeia 2010 edition first enlarged edition2012-11-15虞婧SOP-QC-014-V03按中国药典2010 年版及国家标准GB601-88化学试剂 滴定分析（容量分析）用标准溶液的制备1.增加氯化钡滴定液（C1/2=0.1mol/L） 、亚硝酸钠滴定液（0.1mol/L） 、碘酸钾滴定液（C1/6=0.25mol/L）及溴滴定液（0.05mol/L）的配制及标定方法。According to Pharmacopoeia of Peoples

53、Republic of China, 2010 and GB 60188 of National Standards of Peoples Republic of China, add the preparation and methods of standardization of Barium Chloride (C1/2=0.1mol/L)VS, Sodium Nitrite (0.1mol/L) VS, Potassium Iodate (C1/6=0.25mol/L)VS, Bromine (0.05mol/L) VS.按国家标准 GB601-88化学试剂 滴定分析（容量分析）用标准

54、溶液的制备 ，修订氯化锌滴定液(0.1mol/L)的标定方法。聂曦According to GB 60188 of National Standards of Peoples Republic of China, revise the methods of standardization of Zinc Chloride (0.1mol/L) VS.修订附件内容。2.增加滴定液编号和相对应的溶液的编号。3.修订附件内容。Revise the content of the attachments. Add the number of the volumetric solution and the

55、 matching number of the test solution.1/2附表一：滴定液标定、配制、贮藏参考表 Attached Form 1：Reference table of standardization、Prepared and reposition of volumetric solution 滴定液编号 Volumetric Solution.：34001*碘滴定液 (0.05mol/L) Iodine (0.05mol/L) VS溶液编号 Test Solution:31029*I253.81 12.69g1000ml【配制】Preparation： 取碘 13.0g,

56、加碘化钾 36g 与水 50ml 溶解后，加盐酸 3 滴与水适量使成 1000ml，摇匀，用垂熔玻璃滤器滤过。Dissolve 13.0g of iodine and 36g of potassium iodine in 50 ml of water, add 3 drops of hydrochloric acid and dilute with water to 1000ml, mix well and filter with a sintered glass filter. 【标定】Standardization： 精密量取本液 25.00ml 置于碘量瓶中，加水 100ml 与盐酸溶液

57、（9100）1ml，轻摇混匀，用硫代硫酸钠滴定液(0.1mol/L)滴定，近终点时加 2ml 淀粉指试液，继续滴定至溶液蓝色消失。根据硫代硫酸钠滴定液（0.1mol/L）的消耗量，算出本液的浓度，即得。To 25ml of iodine volumetric solution, aAccurately measured 25ml, in an iodine flask, add 100 ml of water and 1 ml of hydrochloric acid solution（9100）shaking gently, titrate with sodium thiosulfate (

58、0.1mol/L) volumetric solution until towards the end point is nearly reachof tritration，add 2 ml of starch IS and continue titrate until the blue color disappears. Calculate the concentration of the iodine VS according to the volume of the sodium thiosulfate VS consumed. 如需用碘滴定液(0.025mol/L)时，可取碘滴定液(0

59、.05mol/L)加水稀释制成。If iodine (0.025mol/L) VS is needed, dilute the iodine (0.05mol/L) VS with water.【贮藏】Storage：置玻璃塞的棕色玻瓶中，密闭，在凉处保存。 Preserve in a well-closed amber glass bottle, store at a cool place.滴定液编号 Volumetric Solution.：34002*高氯酸滴定液 (0.1mol/L) Perchloric Acid (0.1mol/L)VS溶液编号 Test Solution: 312

60、33*HClO4100.46 10.05g1000ml 【配制】Preparation：取无水冰醋酸（按含水量计算，每 1g 水加醋酐 5.22ml）750ml，加入高氯酸(70%72%)8.5ml，摇匀，在室温下缓缓滴加醋酐 23ml，边加边摇，加完后再振摇均匀，放冷，加无水冰醋酸适量使成 1000ml，摇匀，放置 24 小时。若所测供试品易乙酰化，则须用水分测定法（本版药典二部附录 第一法 A）测定本液的含水量，醋酐调节至本液的含水量为 0.01%0.2%。To 750ml of anhydrous glacial acetic acid add and amount of acetic