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<731>）。
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
美国药典USP31(921)翻译版(上)
