美國(guó)藥典USP31(921)翻譯版(上)

1、921 WATER DETERMINATION水分測(cè)定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(cè)定水分含量對(duì)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(huì)根據(jù)該物品的性質(zhì)，要求使用下面若干方法中的一個(gè)。偶爾，會(huì)允許在2 個(gè)方法中任選一個(gè)。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(cè)量法）、方法 II（恒沸測(cè)量法）、或方法 III（重量分析法），這個(gè)要求在標(biāo)題水分項(xiàng)下給出。The heading Loss on drying (see ) is used in those cases where the loss sustained on

2、heating may be not entirely water.在加熱時(shí)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(jiàn)干燥失重 ）。METHOD I (TITRIMETRIC)方法 I（滴定測(cè)量法）Determine the water by , 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(lái)測(cè)定水分。Method Ia (Direct Titration) 方法 Ia（直接滴定）Principle The titrimetric determination of water

3、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(cè)是基于水與二氧化硫的無(wú)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 dioxid

4、e 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

5、 as the relative concentrations of the Reagent ingredients, the nature of the inert solvent used to1 / 7dissolve 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

6、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 spec

7、imens.在最初的滴定測(cè)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(lái)進(jìn)行該分析。此反應(yīng)的化學(xué)計(jì)算法不夠準(zhǔn)確，并且檢測(cè)的重現(xiàn)性取決于某些因素，例如該試劑成分的相對(duì)濃度、用于溶解供試樣品的惰性溶劑的性質(zhì)、用于具體測(cè)定的方法等。因此，需要應(yīng)用根據(jù)經(jīng)驗(yàn)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(wú)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?jiàn)的供試樣品。儀器：任何能夠充分排除大氣濕度，并能測(cè)定終點(diǎn)的儀器。在直接向無(wú)色溶液

8、滴定的情況下，可以通過(guò)從淡黃色到琥珀色的顏色改變來(lái)觀察此終點(diǎn)。在向供試樣品作殘留滴定的情況下，會(huì)觀察到與此相反的情況。但是，更常見(jiàn)的情況是，使用儀器，利用其中的簡(jiǎn)單電路在浸沒(méi)在待滴定溶液中的一對(duì)白金電極上加上 200mV 的應(yīng)用電壓，從而以電勢(shì)滴定來(lái)測(cè)定終點(diǎn)。在滴定終點(diǎn)，輕微過(guò)量的該試劑會(huì)使電流提高到 50 和 150 微安培，并維持 30 秒到 30 分鐘，具體時(shí)間取決于被滴定的溶液。溶解于該試劑中的物質(zhì)所用時(shí)間是最短的。在一些自動(dòng)滴定儀上，在該終點(diǎn)出現(xiàn)的電流或電壓的突然變化會(huì)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(chǎng)上銷售的儀器通常包含一個(gè)封閉系統(tǒng)，其中由一個(gè)或兩個(gè)自動(dòng)

9、滴定管、一個(gè)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(guò)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(guò)干燥氮?dú)饬骰蚋稍锟諝饬鱽?lái)進(jìn)行凈化。Reagent Prepare the Karl Fischer Reagent as follows. Add 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 p

10、yridine 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,2 / 7transfer the solution to the apparatus, and allow the solution to stand overnight before standardizing. One

11、 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-

12、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(gè) 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(dòng)，緩慢將此溶液加入到放涼后的碘混合物中。搖動(dòng)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(guò)夜。在剛剛配制之后， 1mL此溶液相當(dāng)于約 5mg 水，但是會(huì)逐漸變差；因此，在使用前 1 個(gè)小時(shí)，或在連續(xù)使用時(shí)每日

13、，對(duì)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?？梢允褂檬袌?chǎng)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(chǎng)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(guò)合并存在于兩個(gè)獨(dú)立溶液中的試劑組成部分，在現(xiàn)場(chǎng)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?？梢允褂眉状蓟蚱渌m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 a

14、ccurately 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 us

15、ing 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(guò)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(cè)定的方法。在大多數(shù)情況下，可以使用此公式估計(jì)以毫克計(jì)的供試樣品的最小量：3 / 7FCV/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

16、; 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(jì)； KF是樣品中限度或合理預(yù)期的水含量，為百分比。對(duì)于手

17、動(dòng)滴定， C值在 30%至 100%之間，而對(duì)于儀器方法終點(diǎn)測(cè)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 h

18、igher.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(shí)，打開(kāi)容器，并檢驗(yàn) 10.0mL 混合均勻的樣品。在滴定該樣品過(guò)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(gè)膠囊的混合內(nèi)容物的一部分。Where the specimen under test is tablets, use powder from

19、 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(huì)影響檢驗(yàn)結(jié)果的溫度和相對(duì)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 appropr

20、iate volume of methanol, or other suitable solvent, accurately measured, into a tared container, and shake to dissolve the4 / 7specimen. 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

21、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 sy

22、ringe, 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

23、 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(gè)干燥注射器，注射經(jīng)過(guò)精確稱量的適當(dāng)體積的甲醇或其他適當(dāng)溶劑，至一個(gè)已稱過(guò)皮重的容器，并搖動(dòng)以使該樣品溶解。使用同一個(gè)注射器，從該容器中吸出此溶液并轉(zhuǎn)移至按照步驟項(xiàng)下規(guī)定準(zhǔn)備的一個(gè)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

24、溶液的標(biāo)準(zhǔn)化項(xiàng)下的規(guī)定，測(cè)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(shí)，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(lái)確定試驗(yàn)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 togive the

25、characteristic endpoint color, or 100 50 microamperes of direct c 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 f

26、actor of not more than 2.0. Sodium tartrate may be used as a convenient water reference substance. Quickly add 75 to 125 mg of5 / 7sodium 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 give

27、n by the formula:為了檢測(cè)痕量水份 （少于 1%）最好使用水當(dāng)量因子不超過(guò)2.0 的試劑?？梢允褂镁剖徕c作為便捷的水標(biāo)準(zhǔn)物質(zhì)?？焖偌尤刖芊Q定的75 至 125mg 酒石酸鈉（ C4H4Na2O62H2O），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(jì)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 weigh

28、t, 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

29、 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 . Titrate to the endpoint. Calculate the water equivalence factor, F, in mg of water per mL of reagent, by the formula:為了精確測(cè)定顯著水分含量 （1%或更多），使用純凈水作為標(biāo)準(zhǔn)物質(zhì)。從稱重移液器或者經(jīng)過(guò)預(yù)校準(zhǔn)的注射器或微量移液器中，快速加入經(jīng)過(guò)精密稱定的25 至 50mg 水，加入數(shù)量需取決于該試劑的能力和滴定管的大小，參見(jiàn)稱量器具。滴定至終點(diǎn)。使用下面公式，計(jì)算水分平衡因子 F（單位為每毫升