美國藥典USP31(921)翻譯版(上)

921 WATER DETERMINATION 水分測定水分測定 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 很多藥典物品要么是水合物 要么含有處于吸附狀態(tài)的水 因此 測定水分含量對于證實(shí)與藥典標(biāo) 準(zhǔn)的符合性是很重要的 通常 在具體的各論中會根據(jù)該物品的性質(zhì) 要求使用下面若干方法中的 一個 偶爾 會允許在 2 個方法中任選一個 當(dāng)該物品含有水合狀態(tài)的水 按照具體各論中的規(guī)定 使用方法 I 滴定測量法 方法 II 恒沸測量法 或方法 III 重量分析法 這個要求在標(biāo)題水 分項下給出 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 在加熱時的持續(xù)失重可能不全是水分的情況下 使用標(biāo)題干燥失重 見干燥失重 METHOD I TITRIMETRIC 方法方法 I 滴定測量法 滴定測量法 Determine the water by Method Ia unless otherwise specified in the individual monograph 除非具體各論中另有規(guī)定 使用方法Ia 來測定水分 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 水分的滴定法檢測是基于水與二氧化硫的無水溶液以及存在于緩沖液中與氫離子反應(yīng)的碘之 間的定量反應(yīng) 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 在最初的滴定測量溶液 即卡爾 費(fèi)休試劑 中 二氧化硫和碘溶解于嘧啶和甲醇中 該供試樣品 可以用該試劑直接滴定 或者可以使用殘留滴定程序來進(jìn)行該分析 此反應(yīng)的化學(xué)計算法不夠準(zhǔn)確 并且檢測的重現(xiàn)性取決于某些因素 例如該試劑成分的相對濃度 用于溶解供試樣品的惰性溶劑的 性質(zhì) 用于具體測定的方法等 因此 需要應(yīng)用根據(jù)經(jīng)驗得到的標(biāo)準(zhǔn)化方法 以便實(shí)現(xiàn)預(yù)期的準(zhǔn)確 性 該方法中的精密度很大程度上取決于將大氣濕度從該系統(tǒng)中排除的程度 進(jìn)行水分滴定通常使 用無水甲醇作為供試樣品的溶劑 但是 可以將其他適當(dāng)?shù)娜軇┯糜谔厥饣虿怀Ｒ姷墓┰嚇悠?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 儀器 任何能夠充分排除大氣濕度 并能測定終點(diǎn)的儀器 在直接向無色溶液滴定的情況下 可以 通過從淡黃色到琥珀色的顏色改變來觀察此終點(diǎn) 在向供試樣品作殘留滴定的情況下 會觀察到與 此相反的情況 但是 更常見的情況是 使用儀器 利用其中的簡單電路在浸沒在待滴定溶液中的 一對白金電極上加上 200mV 的應(yīng)用電壓 從而以電勢滴定來測定終點(diǎn) 在滴定終點(diǎn) 輕微過量的 該試劑會使電流提高到 50 和 150 微安培 并維持 30 秒到 30 分鐘 具體時間取決于被滴定的溶液 溶解于該試劑中的物質(zhì)所用時間是最短的 在一些自動滴定儀上 在該終點(diǎn)出現(xiàn)的電流或電壓的突 然變化會使由螺線管操縱的閥門關(guān)閉 該閥門控制者輸送滴定劑的滴定管 市場上銷售的儀器通常 包含一個封閉系統(tǒng) 其中由一個或兩個自動滴定管 一個配備了必須的電極和磁力攪拌器的嚴(yán)密覆 蓋的滴定容器組成 通過適當(dāng)?shù)母稍锲魇瓜到y(tǒng)內(nèi)空氣保持干燥 并且該滴定容器可以通過干燥氮?dú)?流或干燥空氣流來進(jìn)行凈化 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 試劑 按下面方法配制卡爾 費(fèi)休試劑 加入 125 克碘至含有 670mL 甲醇和 170mL 嘧啶的溶液中 放涼 將 100mL 嘧啶置于一個 250mL 量筒中 將該嘧啶置于冰浴中以保持冰冷 送入干燥二氧化 硫直到體積達(dá)到 200mL 伴隨搖動 緩慢將此溶液加入到放涼后的碘混合物中 搖動以使碘溶解 轉(zhuǎn)移此溶液至該儀器 并在標(biāo)準(zhǔn)化之前將該溶液靜置過夜 在剛剛配制之后 1mL 此溶液相當(dāng)于約 5mg 水 但是會逐漸變差 因此 在使用前 1 個小時 或在連續(xù)使用時每日 對其進(jìn)行標(biāo)準(zhǔn)化 使 用中需避光 將該試劑的散裝存貨保存于適當(dāng)密閉的玻璃塞容器中 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 可以使用市場上銷售的卡爾 費(fèi)休類型試劑的穩(wěn)定溶液 也可以使用市場上銷售的試劑 其中含有 除了嘧啶之外的溶劑或鹽基 或除了甲醇之外的醇類 這些可以是通過合并存在于兩個獨(dú)立溶液中 的試劑組成部分 在現(xiàn)場形成的單一的溶液或試劑 如果某些各論中要求使用稀釋后的試劑 則應(yīng) 當(dāng)按照生產(chǎn)商的規(guī)定稀釋 可以使用甲醇或其他適當(dāng)溶劑 例如乙二醇一甲醚 作為稀釋劑 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 供試配制品 除非在具體各論中另有規(guī)定 使用數(shù)量經(jīng)過精確稱定或稱量的供試樣品 其中應(yīng)含水 2 至 250mg 水的數(shù)量取決于試劑的水當(dāng)量因子和終點(diǎn)測定的方法 在大多數(shù)情況下 可以使用此 公式估計以毫克計的供試樣品的最小量 FCV KF in 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 是試劑的水當(dāng)量因子 單位為毫克每毫升 C 是滴定管容量中所使用的體積 為百分比 V 是滴定管體積 以毫升計 KF 是樣品中限度或合理預(yù)期的水含量 為百分比 對于手動滴定 C 值在 30 至 100 之間 而對于儀器方法終點(diǎn)測定 其在 10 至 100 之間 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 如果供試樣品是帶有推進(jìn)劑的氣霧劑 煙霧劑 氣溶膠 將其存放于冷凍室中不少于 2 小時 打 開容器 并檢驗 10 0mL 混合均勻的樣品 在滴定該樣品過程中 在 10 或更高的溫度下確定反應(yīng) 終點(diǎn) Where the specimen under test is capsules use a portion of the mixed contents of not fewer than 4 capsules 如果該供試樣品為膠囊 使用不少于 4 個膠囊的混合內(nèi)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 如果該供試品為片劑 在已知不會影響檢驗結(jié)果的溫度和相對濕度環(huán)境中 將不少于 4 片磨碎至細(xì) 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 如果該各論中顯示此供試樣品易吸濕 使用一個干燥注射器 注射經(jīng)過精確稱量的適當(dāng)體積的甲醇 或其他適當(dāng)溶劑 至一個已稱過皮重的容器 并搖動以使該樣品溶解 使用同一個注射器 從該容 器中吸出此溶液并轉(zhuǎn)移至按照步驟項下規(guī)定準(zhǔn)備的一個滴定容器 使用精確稱量的第二部分甲醇或 其他適當(dāng)溶劑 重復(fù)該步驟 將此洗液加入至滴定容器 并立刻滴定 取與用于溶解樣品以及洗滌 容器和注射器的溶劑同樣體積的一部分溶劑 按照用于殘留滴定的水溶液的標(biāo)準(zhǔn)化項下的規(guī)定 測 定溶劑中的水分含量 以 mg 為單位 并從得自供試樣品滴定的水分含量 以 mg 為單位 中減 去此數(shù)值 在 100 溫度條件下將這些容器及其蓋子干燥 3 小時 在干燥器中靜置至涼 并稱重 根 據(jù)與該容器初始重量的差距 來確定試驗所用的樣品重量 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 試劑的標(biāo)準(zhǔn)化 將足夠的甲醇或其他適當(dāng)溶劑置于滴定容器 以覆蓋電極 并加入充足的試劑 以 產(chǎn)生典型終點(diǎn)顏色 或者在約 200mV 應(yīng)用電壓下產(chǎn)生 100 50 微安培直流電 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 C4H4Na2O6 2H2O 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 為了檢測痕量水份 少于 1 最好使用水當(dāng)量因子不超過 2 0 的試劑 可以使用酒石酸鈉作為便捷 的水標(biāo)準(zhǔn)物質(zhì) 快速加入精密稱定的 75 至 125mg 酒石酸鈉 C4H4Na2O6 2H2O 并滴定至終點(diǎn) 在下面的公式中給出了水平衡因子 F 的計算方法 單位為以每毫升試劑中毫克水 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 是水和酒石酸鈉二水合物的分子量 W 是酒石酸鈉二水合物的重量 單位 mg V 是第二次滴定中消耗的試劑體積 單位 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 t