美国药典USP31(921)翻译版(上).doc

921 WATER DETERMINATION水分测定 Many Pharmacopeial articles either are hydrates or contain water in adsorbed form. As a result, the determination of the water content is important in demonstrating compliance with the Pharmacopeial standards. Generally one of the methods given below is called for in the individual monograph, depending upon the nature of the article. In rare cases, a choice is allowed between 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 individual monograph, and the requirement is given under the heading Water. 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 (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） Determine the water by Method Ia, unless otherwise specified in the individual monograph.除非具体各论中另有规定，使用方法Ia来测定水分。Method Ia (Direct Titration) 方法Ia（直接滴定）Principle The titrimetric determination of water is based upon the quantitative reaction of water with an anhydrous solution of sulfur dioxide and iodine in the presence of a buffer that reacts with hydrogen 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氢离子反应的碘之间的定量反应。In the original titrimetric solution, known as Karl Fischer Reagent, the sulfur dioxide and iodine are dissolved in pyridine and methanol. The test specimen may be titrated with the Reagent directly, or the analysis may be carried out by a residual titration procedure. The stoichiometry of the reaction 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. Therefore, 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 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 observed 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 about 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 being 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 generally 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 nitrogen 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 pyridine, 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 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 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 pyridine 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 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 Preparation Unless otherwise specified in the individual monograph, use an accurately weighed or measured amount of the specimen under test estimated to contain 2 to 250 mg of water. The amount of water depends on the water equivalency factor of the Reagent and on the method of endpoint determination. In most 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 equivalency factor of the Reagent, in mg per mL; C is the used volume, in percent, of the capacity of the buret; V is the buret volume, in mL; and KF is the limit or reasonable expected water content in the sample, in percent. C is between 30% and 100% for manual titration, and between 10% and 100% for the instrumental method endpoint determination.其中，F是试剂的水当量因子，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 the specimen, determine the endpoint 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 specimen under test is capsules, use a portion of the mixed contents of not fewer than 4 capsules.如果该供试样品为胶囊，使用不少于4个胶囊的混合内容物的一部分。Where the specimen under test is tablets, use powder from not fewer than 4 tablets ground to a fine powder in an atmosphere of temperature and relative humidity known not to influence 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 monograph specifies that the specimen under test is hygroscopic, use a dry syringe to inject an appropriate volume of methanol, or other suitable solvent, 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 vessel prepared as directed for Procedure. Repeat the procedure with a second portion of methanol, or other suitable solvent, accurately measured, add this washing to the titration vessel, and immediately titrate. Determine the water content, in mg, of a portion of solvent of the same total volume as that used to dissolve the specimen and to wash the container and syringe, as directed for Standardization of Water Solution for Residual Titrations, and subtract this value from the water content, in mg, obtained in the titration of the specimen under test. Dry the container and its 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。Standardization of the Reagent Place enough methanol or other suitable solvent in the titration vessel to cover the electrodes, and add sufficient Reagent to give the characteristic endpoint color, or 100 50 microamperes of direct current at about 200 mV of applied potential. 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。For determination of trace amounts of water (less than 1%), it is preferable to use Reagent with a water equivalency factor of not more than 2.0. Sodium tartrate may be used as a convenient water reference substance. Quickly add 75 to 125 mg of sodium tartrate (C4H4Na2O62H2O), accurately weighed by difference, and titrate to the endpoint. The water equivalence factor F, in mg of water per mL of reagent, is given 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（C4H4Na2O62H2O），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 18.02 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 Reagent consumed in the second titration.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mL）。For the precise determination of significant amounts of water (1% or more), use Purified Water as the reference substance. Quickly add between 25 and 250 mg of water, accurately weighed by difference, from a weighing pipet or from a precalibrated syringe or micropipet, the amount taken being governed by the reagent strength and the buret size, as referred to under Volumetric Apparatus 31. Titrate to the endpoint. Calculate the water equivalence factor, F, in mg of water per mL of reagent, by the formula: 为了精确测定显著水分含量（1%或更多），使用纯净水作为标准物质。从称重移液器或者经过预校准的注射器或微量移液器中，快速加入经过精密称定的25至50mg水，加入数量需取决于该试剂的能力和滴定管的大小，参见称量器具。滴定至终点。使用下面公式，计算水分平衡因子F（单位为每毫升试剂中毫克水）。W/V,in which W is the weight, in mg, of the water; and V is the volume, in mL, of the reagent required.其中W是水的重量（单位mg）；V是需要的试剂体积（单位mL）。Procedure Unless otherwise specified, transfer 35 to 40 mL of methanol or other suitable solvent to the titration vessel, and titrate with the Reagent to the electrometric or visual endpoint to consume any moisture that may be present. (Disregard the volume consumed, since it does not enter into the calculations.) Quickly add the Test Preparation, mix, and again titrate with the Reagent to the electrometric or visual endpoint. Calculate the water content of the specimen, in mg, taken by the formula: 步骤：除非另有规定，转移35至40mL甲醇或其他适当溶剂至滴定容器，并使用该试剂进行滴定至测电法或视觉观察的终点，以消耗掉可能存在的任何水分。（不要理会消耗的体积，因为其不会带入计算。）快速加入供试配制液，混匀，并再次使用试剂滴定至测电法或视觉观察的终点。使用下面的公式，计算样品中的水分含量：SF,in which S is the volume, in mL, of the Reagent consumed in the second titration; and F is the water equivalence factor of the Reagent. 其中，S是在第二次滴定中消耗掉的试剂体积（单位mL）；F是该试剂的水平衡因子。