美国药典USP31(921)翻译版(上)

1、921 WATER DETERMINATION 水分测定Many Pharmacopeial articles either are hydrates or contain water in adsorbed form. As a result, the determ in ati on of the water content is importa nt in dem on strat ing complia nee with thePharmacopeial sta ndards. Gen erally one of the methods give n below is called f

2、or in the in dividual mono graph, depe nding upon the n ature of the article. In rare cases, a choice is allowed betwee n two methods. When the article contains water of hydration, the Method I (Titrimetric), the Method II (Azeotropic), or the Method III (Gravimetric) is employed, as directed in the

3、 in dividual mono graph, and the requireme nt is give n un der the head ingWater.很多药典物品要么是水合物，要么含有处于吸附状态的水。因此，测定水分含量对于证实与药典标准 的符合性是很重要的。通常，在具体的各论中会根据该物品的性质，要求使用下面若干方法中的一个。 偶尔，会允许在2个方法中任选一个。当该物品含有水合状态的水，按照具体各论中的规定，使用方 法I (滴定测量法)、方法II (恒沸测量法)、或方法III (重量分析法)，这个要求在标题 水分项下 给出。The heading Loss on drying (

4、see Loss on Drying 731 ) is used in those cases where the loss sustained on heating may be not entirely water.在加热时的持续失重可能不全是水分的情况下，使用标题干燥失重(见干燥失重)。METHOD I (TITRIMETRIC) 方法 I (滴定测量法)Determi ne the water by Method Ia, uni ess otherwise specified in the in dividual mono graph. 除非具体各论中另有规定，使用 方法Ia来测定水分

5、。Method Ia (Direct Titration)方法 Ia (直接滴定)Prin ciple The titrimetric determ in ati on of water is based upon the qua ntitative react ion of water with an an hydrous soluti on of sulfur dioxide and iod ine in the prese nee of a buffer that reacts with hydroge n ions.原理：水分的滴定法检测是基于水与二氧化硫的无水溶液以及存在于缓冲液中与

6、氢离子反应的碘之间 的定量反应。In the orig inal titrimetric soluti on, known as Karl Fischer Reage nt, the sulfur dioxide and iodi ne are dissolved in pyridi ne and metha nol. The test specime n may be titrated with the Reage nt directly, or the an alysis may be carried out by a residual titrati on procedure. The

7、stoichiometry of the react ion is not exact, and the reproducibility of a determination depends upon such factors as the relative concentrations of the Reagent ingredients, the nature of the inert solvent used to dissolve the test specimen, and the technique used in the particular determination. The

8、refore, an empirically standardized technique is used in order to achieve the desired accuracy. Precision in the method is governed largely by the extent to which atmospheric moisture is excluded from the system. The titration of water is usually carried out with the use of anhydrous methanol as the

9、 solvent for the test specimen; however, other suitable solvents may be used for special or unusual test specimens. 在最初的滴定测量溶液（即卡尔费休试剂）中，二氧化硫和碘溶解于嘧啶和甲醇中。该供试样品可 以用该 试剂直接滴定，或者可以使用残留滴定程序来进行该分析。 此反应的化学计算法不够准确， 并 且检测的重现性取决于某些因素， 例如该试剂成分的相对浓度、 用于溶解供试样品的惰性溶剂的性质、 用于具体测定的方法等。因此，需要应用根据经验得到的标准化方法，以便实现预期的准确性。该方

10、 法中的精密度很大程度上取决于将大气湿度从该系统中排除的程度。 进行水分滴定通常使用无水甲醇 作为供试样品的溶剂；但是，可以将其他适当的溶剂用于特殊或不常见的供试样品。Apparatus Any apparatus may be used that provides for adequate exclusion of atmospheric moisture and determination of the endpoint. In the case of a colorless solution that is titrated directly, the endpoint may be o

11、bserved visually as a change in color from canary yellow to amber. The reverse is observed in the case of a test specimen that is titrated residually. More commonly, however, the endpoint is determined electrometrically with an apparatus employing a simple electrical circuit that serves to impress a

12、bout 200 mV of applied potential between a pair of platinum electrodes immersed in the solution to be titrated. At the endpoint of the titration a slight excess of the reagent increases the flow of current to between 50 and 150 microamperes for 30 seconds to 30 minutes, depending upon the solution b

13、eing titrated. The time is shortest for substances that dissolve in the reagent. With some automatic titrators, the abrupt change in current or potential at the endpoint serves to close a solenoid-operated valve that controls the buret delivering the titrant. Commercially available apparatus general

14、ly comprises a closed system consisting of one or two automatic burets and a tightly covered titration vessel fitted with the necessary electrodes and a magnetic stirrer. The air in the system is kept dry with a suitable desiccant, and the titration vessel may be purged by means of a stream of dry n

15、itrogen or current of dry air. 仪器：任何能够充分排除大气湿度，并能测定终点的仪器。在直接向无色溶液滴定的情况下，可以通 过从淡黄色到琥珀色的颜色改变来观察此终点。 在向供试样品作残留滴定的情况下， 会观察到与此相 反的情况。但是，更常见的情况是，使用仪器，利用其中的简单电路在浸没在待滴定溶液中的一对白金电极上加上 200mV 的应用电压，从而以电势滴定来测定终点。在滴定终点，轻微过量的该试剂会 使电流提高到 50 和 150 微安培， 并维持 30 秒到 30 分钟，具体时间取决于被滴定的溶液。 溶解于该 试剂中的物质所用时间是最短的。 在一些自动滴定仪上， 在

16、该终点出现的电流或电压的突然变化会使 由螺线管操纵的阀门关闭， 该阀门控制者输送滴定剂的滴定管。 市场上销售的仪器通常包含一个封闭 系统，其中由一个或两个自动滴定管、 一个配备了必须的电极和磁力搅拌器的严密覆盖的滴定容器组 成。通过适当的干燥器使系统内空气保持干燥， 并且该滴定容器可以通过干燥氮气流或干燥空气流来 进行净化。Reagent Prepare the Karl Fischer Reagent as follows. Add 125 g of iodine to a solution containing 670 mL of methanol and 170 mL of pyridi

17、ne, and cool. Place 100 mL of pyridine in a 250-mL graduated cylinder, and, keeping the pyridine cold in an ice bath, pass in dry sulfur dioxide until the volume reaches 200 mL. Slowly add this solution, with shaking, to the cooled iodine mixture. Shake to dissolve the iodine, transfer the solution

18、to the apparatus, and allow the solution to stand overnight before standardizing. One mL of this solution when freshly prepared is equivalent to approximately 5 mg of water, but it deteriorates gradually; therefore, standardize it within 1 hour before use, or daily if in continuous use. Protect from

19、 light while in use. Store any bulk stock of the reagent in a suitably sealed, glass-stoppered container, fully protected from light, and under refrigeration.试剂：按下面方法配制卡尔费休试剂。加入125克碘至含有670mL甲醇和170mL嘧啶的溶液中，放凉。将 100mL 嘧啶置于一个 250mL 量筒中，将该嘧啶置于冰浴中以保持冰冷，送入干燥二氧化 硫直到体积达到 200mL 。伴随摇动，缓慢将此溶液加入到放凉后的碘混合物中。摇动以使碘

20、溶解， 转移此溶液至该仪器，并在标准化之前将该溶液静置过夜。在刚刚配制之后， 1mL 此溶液相当于约 5mg 水，但是会逐渐变差；因此，在使用前 1 个小时，或在连续使用时每日，对其进行标准化。使 用中需避光。将该试剂的散装存货保存于适当密闭的玻璃塞容器中，完全避光，并冷藏。A commercially available, stabilized solution of Karl Fischer type reagent may be used. Commercially available reagents containing solvents or bases other than py

21、ridine or alcohols other than methanol may be used also. These may be single solutions or reagents formed in situ by combining the components of the reagents present in two discrete solutions. The diluted Reagent called for in some monographs should be diluted as directed by the manufacturer. Either

22、 methanol or other suitable solvent, such as ethylene glycol monomethyl ether, may be used as the diluent.可以使用市场上销售的卡尔费休类型试剂的稳定溶液。也可以使用市场上销售的试剂，其中含有除 了嘧啶之外的溶剂或盐基， 或除了甲醇之外的醇类。 这些可以是通过合并存在于两个独立溶液中的试剂组成部分，在现场形成的单一的溶液或试剂。如果某些各论中要求使用稀释后的试剂，则应当按照 生产商的规定稀释。可以使用甲醇或其他适当溶剂，例如乙二醇一甲醚，作为稀释剂。Test Preparati on Un

23、less otherwise specified in the in dividual mono graph, use an accurately weighed or measured amount of the specime n un der test estimated to contain 2 to 250 mg of water. The amount of water depe nds on the water equivale ncy factor of theReage nt and on the method ofendpoint determination. In mos

24、t cases, the minimum amount of specimen, in mg, can be estimated using the formula:供试配制品：除非在具体各论中另有规定，使用数量经过精确称定或称量的供试样品，其中应含水2至250mg。水的数量取决于试剂的水当量因子和终点测定的方法。在大多数情况下，可以使用此公 式估计以毫克计的供试样品的最小量：FCV/KFin which F is the water equivale ncy factor of the Reage nt, in mg per mL; C is the used volume, in perc

25、ent, of the capacity of the buret; V is the buret volume, in mL; and KF is the limit or reas on able expected water content in the sample, in perce nt. C is betwee n 30% and 100% for manual titratio n, and betwee n 10% and 100% for the in strume ntal method en dpo int determ in ati on.其中，F是试剂的水当量因子，

26、单位为毫克每毫升；C是滴定管容量中所使用的体积（为百分比）；V是滴定管体积，以毫升计；KF是样品中限度或合理预期的水含量，为百分比。对于手动滴定，C值在30%至100%之间，而对于仪器方法终点测定，其在10%至100%之间。Where the specimen under test is an aerosol with propellant, store it in a freezer for not less than 2 hours, open the container, and test 10.0 mL of the well-mixed specimen. In titrating

27、the specimen, determ ine the en dpo int at a temperature of 10 or higher.如果供试样品是带有推进剂的气雾剂（烟雾剂、气溶胶），将其存放于冷冻室中不少于2小时，打开容器，并检验10.0mL混合均匀的样品。在滴定该样品过程中，在10或更高的温度下确定反应终点。Where the specime n un der test is capsules, use a porti on of the mixed contents of not fewer tha n 4 capsules.如果该供试样品为胶囊，使用不少于4个胶囊的混合内

28、容物的一部分。Where the specime n un der test is tablets, use powder from not fewer tha n 4 tablets ground to a fine powder in an atmosphere of temperature and relative humidity known not to in flue nee the results.如果该供试品为片剂，在已知不会影响检验结果的温度和相对湿度环境中，将不少于4片磨碎至细粉末。Where the mono graph specifies that the specim

29、e n un der test is hygroscopic, use a dry syri nge to inject an appropriate volume of metha nol, or other suitable solve nt, accurately measured, into a tared container, and shake to dissolve the specimen. Using the same syringe, remove the solution from the container and transfer it to a titration

30、vessel prepared as directed for Procedure. Repeat the procedure with a sec ond porti on of metha nol, or other suitable solve nt, accurately measured, add this washing to the titration vessel, and immediately titrate. Determine the water content, in mg, of a porti on of solve nt of the same total vo

31、lume as that used to dissolve the specime n and to wash the container and syri nge, as directed forStan dardizati on of Water Soluti on for Residual Titrati ons,and subtract this value from the water conten t, i n mg, obta ined in the titrati on of the specime n un der test. Dry the container and it

32、s closure at 100- for 3 hours, allow to cool in a desiccator, and weigh.Determine the weight of specimen tested from the difference in weight from the initial weight of the container.如果该各论中显示此供试样品易吸湿，使用一个干燥注射器，注射经过精确称量的适当体积的甲醇或其他适当溶剂，至一个已称过皮重的容器，并摇动以使该样品溶解。使用同一个注射器，从该容器中 吸出此溶液并转移至按照步骤项下规定准备的一个滴定容器。使

33、用精确称量的第二部分甲醇或其他适 当溶剂，重复该步骤，将此洗液加入至滴定容器，并立刻滴定。取与用于溶解样品以及洗涤容器和注 射器的溶剂同样体积的一部分溶剂，按照用于残留滴定的水溶液的标准化 项下的规定，测定溶剂中的水分含量（以mg为单位），并从得自供试样品滴定的水分含量（以 mg为单位）中减去此数值。在 100-1温度条件下将这些容器及其盖子干燥 3小时，在干燥器中静置至凉，并称重。根据与该容器初 始重量的差距，来确定试验所用的样品重量。Stan dardizati on of the Reage nt Place eno ugh metha nol or other suitable sol

34、ve nt in the titratio n vessel to cover the electrodes, and add sufficie nt Reage nt to give the characteristic en dpo int color, or 1000 microamperes of direct curre nt at about 200 mV of applied pote ntial.试剂的标准化：将足够的甲醇或其他适当溶剂置于滴定容器，以覆盖电极，并加入充足的试剂，以产生典型终点颜色，或者在约200mV应用电压下产生100 50微安培直流电。Reage nt wi

35、th aFor determ in atio n of trace amounts of water （less tha n 1%）, it is preferable to use water equivale ncy factor of not more tha n 2.0. Sodium tartrate may be used as a convenient waterreferenee substanee. Quickly add 75 to 125 mg of sodium tartrate （C4H4Na2O6 2H2O）, accuratelyweighed by differ

36、e nee, and titrate to the en dpo int. The water equivale nee factor F, in mg of water per mL of reage nt, is give n by the formula:为了检测痕量水份（少于1%）最好使用水当量因子不超过 2.0的试剂。可以使用酒石酸钠作为便捷 的水标准物质。快速加入精密称定的 75至125mg酒石酸钠（CqNazOe 2出0），并滴定至终点。 在下面的公式中给出了水平衡因子 F的计算方法（单位为以每毫升试剂中毫克水）：2（18.02/230.08）（ W/V）,in which 18

37、.02 and 230.08 are the molecular weights of water and sodium tartrate dihydrate, respectively; W is the weight, in mg, of sodium tartrate dihydrate; and V is the volume, in mL, of the Reage nt con sumed in the sec ond titrati on.其中，18.02和230.08是水和酒石酸钠二水合物的分子量；W是酒石酸钠二水合物的重量（单位mg）； V是第二次滴定中消耗的 试剂体积（单位

38、mL）。For the precise determ in ati on of sig nifica nt amounts of water （1% or more）, use Purified Water as the refere nee substa nee. Quickly add betwee n 25 and 250 mg of water, accurately weighed by differenee, from a weighing pipet or from a precalibrated syringe or micropipet, the amount taken being gover ned by the reage nt stre ngth and the buret size, as referred to un derVolumetric