链接放头前儿吧，方便你从开头看。
歪翻USP44: 1231 制药用水 （1）（
歪翻USP44: 1231 制药用水 （1））
歪翻USP44: 1231 制药用水 （1）） 歪翻USP44: 1231 制药用水（2）（歪翻USP44: 1231 制药用水（2））
歪翻USP44: 1231 制药用水（2）） 3.3Nonmonographed Waters
In addition to the bulk monographed waters described above, nonmonographed waters can also be used in pharmaceutical processing steps such as cleaning and synthetic steps, and also as a starting material for further purification or testing purposes. Unless otherwise specified in the compendium, the minimum quality of water is Purified Water. [NOTE—The information in this chapter is not an all-inclusive discussion of all nonmonographed waters identified in the USP–NF.]
除了上述散装专论水外，非专论水也可用于药物工艺步骤，如清洗和合成步骤，也可作为进一步净化或测试目的的起始材料。除药典中另有规定外，水的最低质量为纯化水。[注-本章信息不是对USP-NF中确定的所有非专著水的全面讨论。]
3.3.1DRINKING WATER
Drinking Water can be referred to as Potable Water (meaning drinkable or fit to drink), National Primary Drinking Water, Primary Drinking Water, or EPA Drinking Water. Except where a singular drinking water specification is stated (such as the U.S. EPA’s NPDWR, as cited in 40 CFR Part 141), this water must comply with the quality attributes of either the NPDWR or the drinking water regulations of the EU or Japan, or the WHO Guidelines for Drinking-Water Quality. Drinking Water may originate from a variety of sources including a public water supply, a private water supply (e.g., a well), or a combination of these sources (see 2. Source Water Considerations).
饮用水可以被称为可饮用水(指可饮用或适合饮用)、国家初级饮用水、初级饮用水或EPA饮用水。除非声明了单一的饮用水规范(如美国EPA的NPDWR，引用于40 CFR第141部分)，否则这种水必须符合NPDWR或欧盟或日本的饮用水法规或世界卫生组织饮用水质量指南的质量属性。饮用水可以来自各种来源，包括公共供水、私人供水(例如，井)或这些来源的组合(见2)。水源问题)。
Drinking Water may be used in the early stages of cleaning pharmaceutical manufacturing equipment and product-contact components. Drinking Water is also the minimum quality of water that should be used for the preparation of official substances and other bulk pharmaceutical ingredients. Where compatible with the processes, the contaminant levels allowed in Drinking Water are generally considered safe for use in preparing official substances and other drug substances. However, where required by the processing of the materials to achieve their required final purity, higher qualities of water may be needed for these manufacturing steps, perhaps even water as pure as Water for Injection or Purified Water. Such higher-purity waters, however, might require only selected attributes to be of higher purity than Drinking Water (see Figure 2a and Figure 2b). Drinking Water is the prescribed source or feed water for the production of bulk monographed pharmaceutical waters. The use of Drinking Water specifications establishes a reasonable set of maximum allowable levels of chemical and microbiological contaminants with which a water purification system will be challenged. Because seasonal variations in the quality attributes of the Drinking Water supply can occur, it is important to give due consideration to its uses. The processing steps in the production of pharmaceutical waters must be designed to accommodate this variability.
饮用水可用于制药生产设备和产品接触部件的早期清洗阶段。饮用水也是应用于制备官方物质和其他原料药成分的最低水质。在与生产工艺相兼容的情况下，饮用水中允许的污染物水平通常被认为是安全的，可用于制备官方物质和其他药物物质。然而，在材料加工过程中需要达到最终所需的纯度时，这些制造步骤可能需要更高质量的水，甚至可能需要像注射用水或纯化水那样纯净的水。然而，这种高纯度的水可能只要求选定的属性比饮用水的纯度高(见图2a和图2b)。饮用水是批量生产药典药品用水的规定水源或给水。饮用水规范的使用，建立了一套防止水净化系统面临威胁的合理的化学和微生物污染物的最大允许水平。由于饮用水供应质量属性会发生季节性变化，因此充分考虑其使用是很重要的。制药用水生产中的加工步骤必须设计适应这种变化。
Figure 2a. Selection of water for pharmaceutical purposes: APIs and dosage forms.
图2a. 制药用水的选择:原料药和剂型
Figure 2b. Selection of water for pharmaceutical purposes: Analytical reagents.
图2b. 制药用水的选择:分析试剂
3.3.2OTHER NONMONOGRAPHED WATERS
In addition to Drinking Water, this compendium discusses waters with various other designations. These include waters of various quality levels for special uses such as, but not limited to, cleaning and testing purposes.
除饮用水外，本纲要还讨论了具有各种其他名称的水。这些水质包括各种特殊用途的水质，例如但不限于清洁和测试用途。
Both General Notices and Requirements (see General Notices, 8.230.30 Water in a Compendial Procedure) and Reagents, Indicators, and Solutions clearly state that where the term “water” is indicated for use in analyses without grammatical qualification or other specification, the quality of the water must be Purified Water. However, numerous such qualifications do exist. Some of these qualifications involve adjectives describing methods of preparation, ranging from specifying the primary purification step to specifying additional purification. Other qualifications call for specific attribute “absences” to be met that might otherwise interfere with analytical processes. In most of these cases, the required attribute absences are not specifically tested. Sometimes, a further “purification process” is specified that ostensibly allows the water to adequately meet this required “absence attribute”.
凡例和要求(见凡例，8.230.30 药典程序中的水 )以及试剂、指示剂和溶液，都明确规定，在没有语义上的确认或其他规范的分析中使用术语“水”时，水的质量必须是纯化水。然而，这样的条件确实存在。其中一些条件涉及描述制备方法的形容词，范围从指定初级纯化步骤到指定附加纯化。其他条件要求满足“不得含有”的特定属性，否则可能会干扰分析过程。在大多数情况下，这些特性没有专门测试。有时，还需要进一步的“净化过程”，以期使其充分满足这一特性。
However, preparation instructions for many reagents were carried forward from the innovator’s laboratories to the originally introduced monograph for a particular USP–NF article or general test chapter. The quality of the reagent water described in these tests may reflect the water quality designation of the innovator’s laboratory. These specific water designations may have originated without the innovator’s awareness of the requirement for Purified Water in USP–NF tests. Regardless of the original reason for the creation of these numerous special analytical waters, it is possible that the attributes of these special waters could now be met by the basic preparation steps and current specifications of Purified Water. In some cases, however, some of the cited post-processing steps are still necessary to reliably achieve the required attributes.
然而，许多试剂的制备说明从创新者的实验室延续到最初介绍的特定USP-NF各论或通用测试专论。在这些试验中所描述的试剂水的质量可以反映创新者实验室的水质设计。这些特定的水的命名可能是在发明者没有意识到USP-NF测试中需要纯化水的情况下产生的。不管创造这些特殊分析水的最初原因是什么，这些特殊水的属性现在可以通过基本的制备步骤和当前纯化水的规格来满足。然而，在某些情况下，为了可靠地实现所需的属性，仍然需要一些引用的后处理步骤。
Users are not obligated to utilize specific and perhaps archaically generated forms of analytical water where alternatives with equal or better quality, availability, or analytical performance may exist. The consistency and reliability of operations for producing these alternative analytical waters should be verified so that the desired attributes are produced. In addition, any alternative analytical water must be evaluated on an application-by-application basis by the user to ensure its suitability. The following is a summary of the various types of nonmonographed analytical waters that are cited in the USP–NF. This is not an exhaustive listing. Those listed below are used in multiple locations. Several nonmonographed analytical waters are not included below because they are only found in one or perhaps two locations within this compendium.
用户没有义务使用特定的、可能是过时的分析水形式，因为可能存在同等或更好质量、可用性或分析性能的替代品。生产这些替代分析水的操作的一致性和可靠性应得到验证，以便生产所需的属性。此外，任何可供选择的分析用水都必须由用户在逐个应用的基础上进行评估，以确保其适用性。以下是USP-NF中引用的各种类型的非专论分析水的摘要。下面列出的这些分析用水在多个位置被引述，这不是一个详尽的清单。一些非专论的分析水不包括在下面，因为它们只在本概要内有一两个引述。
Note that the names of many of the waters below imply a very low chemical impurity level. For example, “deionized water” implies that all the ions have been removed. However, in most cases discussed below, exposure of the water to air will result in the ingress of carbon dioxide (CO2), leading to the formation of bicarbonate and hydrogen ions. Therefore, the removal of ions cannot be completely maintained for most analytical applications.
请注意，以下许多水的名称暗示了非常低的化学杂质水平。例如，“去离子水”意味着所有的离子都被去除了。然而，在下面讨论的大多数情况下，水暴露在空气中会导致二氧化碳(CO2)的进入，导致碳酸氢盐和氢离子的形成。因此，对于大多数分析应用来说，离子的去除不能完全保持。
3.3.3AMMONIA-FREE WATER
From a functional standpoint, Ammonia-Free Water must have a negligible ammonia concentration to avoid interference in tests sensitive for or to ammonia. Due to the nature of the uses of this water, Purified Water could be a reasonable alternative for these applications.
从功能的角度来看，无氨水的氨浓度必须可以忽略不计，以避免干扰氨敏感的试验。由于这种水的使用性质，纯化水可能是这些应用的合理替代品。
3.3.4CARBON DIOXIDE-FREE WATER
Carbon dioxide-free water is defined in the Reagents, Indicators, and Solutions section of USP–NF as Purified Water that has been vigorously boiled for NLT 5 min, then cooled and protected from absorption of atmospheric carbon dioxide. Alternatively, this could be Purified Water that has a resistivity of NLT 18 megohm-cm at 25°.
在USP-NF的试剂、指标和溶液部分中，无二氧化碳水被定义为经过NLT剧烈煮沸5分钟，然后冷却并防止大气二氧化碳吸收的纯化水。或者，可以是在25°的电阻率为NLT 18兆欧/厘米的纯化水。
Because the absorption of atmospheric carbon dioxide lowers the pH of high-purity waters, most of the uses of Carbon Dioxide-Free Water are either associated as a solvent in pH-related or pH-sensitive determinations or as a solvent in bicarbonate-sensitive reagents or determinations.
由于大气中二氧化碳的吸收降低了高纯水的pH值，无二氧化碳水的大多数用途要么在pH相关或pH敏感的测定中作为溶剂，要么在碳酸氢盐敏感试剂或测定中作为溶剂。
The term “Carbon Dioxide-Free Water” is sometimes used improperly. Besides its use for pH or acidity/alkalinity tests, the purpose for using this water is not always clear. The intention could be to use water that was deaerated (free of dissolved air) or deionized (free of extraneous ions), or even Purified Water with an additional boiling step. Although boiling is highly effective for removing carbon dioxide as well as all other dissolved gasses, these gases are readily re-absorbed unless the water is protected. Even with protection, such as use of a stoppered container, re-absorption will occur over time as air will readily transmit through seals and diffuse through most materials. Deionization is also an efficient process for removing dissolved carbon dioxide. Carbon dioxide forms ionic bicarbonate in water, and will be subsequently removed by ion-exchange resins. However, the same problem of carbon dioxide re-absorption will occur after the deionized water is exposed to air. Also, the deionization approach for creating Carbon Dioxide-Free Water does not deaerate the water or remove other dissolved gases such as oxygen (O2); it only removes carbon dioxide and other ions.
“无二氧化碳水”这个词有时使用不当。除了用于pH或酸度/碱度测试外，使用这种水的目的并不总是明确的。目的可能是使用除氧(不含溶解空气)或去离子(不含外来离子)的水，甚至是经过额外煮沸步骤的纯化水。尽管沸水对于去除二氧化碳和所有其他溶解气体非常有效，但除非水被保护起来，否则这些气体很容易被重新吸收。即使有保护，如使用一个塞子容器，重新吸收将发生随着时间的推移，因为空气将很容易通过密封传播和扩散到大多数材料。去离子化也是去除溶解二氧化碳的有效方法。二氧化碳在水中形成碳酸氢盐离子，随后用离子交换树脂除去。然而，去离子水暴露在空气中后，同样会出现二氧化碳再吸收的问题。此外，用于生成无二氧化碳水的去离子化方法不会除氧或除去其他溶解气体，如氧气(O2);它只能去除二氧化碳和其他离子。
Depending on the application, Purified Water may meet the requirements where Carbon Dioxide-Free Water is called for. This could also include pH or acidity or alkalinity tests. The pH of a sample of pure Deionized Water is, by definition, 7.0. When that same sample is exposed to typical environmental atmospheric conditions, the water sample will absorb carbon dioxide and result in a pH range of approximately 5.4–6.2 ([H+] is in the range of 4.0 × 10–6 M to 6.3 × 10–7 M). The added acidity caused by carbon dioxide absorption may be insignificant compared to the material being analyzed.
根据应用的不同，纯化水可能是满足要求的无二氧化碳水。这也可以包括pH值或酸度或碱度测试。根据定义，纯去离子水样品的pH值为7.0。当同样的样品暴露在典型的环境大气条件下时，水样将吸收二氧化碳，其pH值范围约为5.4-6.2 ([H+]在4.0 × 10-6 M到6.3 × 10-7 M之间)。与被分析材料相比，二氧化碳吸收引起的增加酸度可能不显著。
3.3.5DISTILLED WATER
Distilled Water is produced by vaporizing Drinking Water or a higher quality of water and condensing it into a purer state. It is used primarily as a solvent for reagent preparation, and it is also specified in the execution of other aspects of tests, such as for rinsing an analyte, transferring a test material as a slurry, as a calibration standard or analytical blank, and for test apparatus cleaning. Distilled Water is also cited as the starting water to be used for making High-Purity Water (see
3.3.10 High-Purity Water). Because none of the cited uses of this water imply a need for a particular purity attribute that can only be derived by distillation, water meeting the requirements for Purified Water derived by other means of purification or Water for Injection could be equally suitable where Distilled Water is specified. It is the user’s responsibility to verify the suitability of Purified Water or Water for Injection.
蒸馏水是通过将饮用水或更高质量的水蒸发并将其冷凝成更纯净的状态而产生的。它主要用作试剂制备的溶剂，也用于执行测试的其他方面，如冲洗分析物，转移测试材料作为浆料，作为校准标准或分析空白，以及测试仪器清洗。蒸馏水也被引用为用于制造高纯水的起始水(见3.3.10)高纯度水)。因为引用的这些水的用途中没有一个意味着需要某种只能通过蒸馏获得的特定纯度属性，所以满足通过其他纯化方法获得的纯化水或注射用水的要求的水可以同样适用于指定蒸馏水的地方。验证纯化水或注射用水的适用性是用户的责任。
3.3.6FRESHLY DISTILLED WATER
Freshly Distilled Water or “recently distilled water” is produced in the same manner as Distilled Water and should be used soon after its generation. This implies the need to avoid endotoxin contamination, as well as any other forms of contamination from the air or containers, that could arise with prolonged storage. Freshly Distilled Water is used for preparing solutions for subcutaneous test-animal injections and for a reagent solvent in tests for which there appears to be no particularly high water purity needed that could be ascribable to being “freshly distilled”. In the test-animal application, the term “freshly distilled” and its testing use imply a chemical, endotoxin, and microbiological purity that could be equally satisfied by Water for Injection (although no reference is made to these chemical, endotoxin, or microbial attributes or specific protection from recontamination). For non-animal uses, water meeting the requirements for Purified Water derived by other means of purification and/or storage periods could be equally suitable where “recently distilled water” or Freshly Distilled Water is specified. It is the user’s responsibility to verify the suitability of Purified Water or Water for Injection.
新鲜蒸馏水或“新近蒸馏水”是以蒸馏水相同的方式生产的，并应在其产生后不久使用。这意味着需要避免内毒素污染，以及来自空气或容器的任何其他形式的污染，这些污染可能因长期储存而产生。新鲜蒸馏水用于制备皮下实验动物注射用溶液和在似乎不需要特别高的水纯度的试验中用作试剂溶剂，而这种水纯度可归因于"新鲜蒸馏水"。在动物实验应用中，术语“新鲜蒸馏”及其测试用途意味着化学、内毒素和微生物纯度，可以通过注射用水同样满足(尽管没有提及这些化学、内毒素或微生物属性或防止再污染的具体保护)。对于非动物用途，满足通过其他净化方法和/或储存期获得的纯化水要求的水，在指定为“最近蒸馏水”或新蒸馏水时，也同样适用。验证纯化水或注射用水的适用性是用户的责任。
3.3.7DEIONIZED WATER
Deionized Water can be produced by starting with either Drinking Water or Purified Water, depending upon monograph or testing procedures defined in the compendia. Deionized Water is produced by an ion-exchange process in which the cations and anions are replaced with H+ and OH− ions by use of ion-exchange resins. Similar to Distilled Water, Deionized Water is used primarily as a solvent for reagent preparation, but it is also specified in the execution of other aspects of tests, such as for transferring an analyte within a test procedure, as a calibration standard or analytical blank, and for test apparatus cleaning. Also, none of the cited uses of this water imply any needed purity attribute that can only be achieved by deionization. Therefore, water meeting the requirements for Purified Water that is derived by other means of purification could be equally suitable where Deionized Water is specified. It is the user’s responsibility to verify the suitability of Purified Water.
去离子水可以从饮用水或纯化水开始生产，这取决于各论或通则中定义的测试程序。去离子水是由离子交换过程产生的，其中阳离子和阴离子被使用离子交换树脂的H+和OH−离子取代。与蒸馏水类似，去离子水主要用作试剂制备的溶剂，但它也用于执行测试的其他方面，如在测试程序中转移分析物，作为校准标准或分析空白，以及测试仪器的清洗。此外，没有引用使用这种水意味着任何需要的纯度属性，只能通过去离子化来实现。因此，通过其他净化方法得到的满足纯化水要求的水可以同样适用于指定去离子水的地方。验证纯化水的适用性是用户的责任。
3.3.8DEIONIZED DISTILLED WATER
Deionized Distilled Water is produced by deionizing (see 3.3.7 Deionized Water) Distilled Water. This water is used as a reagent in a liquid chromatography test that requires a low ionic or organic impurity level. Because of the importance of this high purity, water that meets the requirements for Purified Water may not be acceptable. High-Purity Water (see 3.3.10 High-Purity Water) could be a reasonable alternative to this water. It is the user’s responsibility to verify the suitability of the alternative water used.
去离子蒸馏水是通过去电离蒸馏水(参见3.3.7去离子水)产生的。这种水在需要低离子或有机杂质水平的液相色谱测试中用作试剂。由于这种高纯度的重要性，满足纯化水要求的水可能不被接受。高纯水(见3.3.10高纯水)可以作为这种水的合理替代品。用户有责任核实所使用的替代水的适用性。
3.3.9FILTERED WATER
Filtered Water is Purified Water that has been filtered to remove particles that could interfere with the analysis where this water is specified. It is sometimes used synonymously with Particle-Free Water and Ultra-Filtered Water and is cited in some monographs and general chapters as well as in Reagents, Indicators, and Solutions. Depending on its referenced location in USP– NF, it is variously defined as water that has been passed through filters rated as 1.2, 0.2, or 0.22 µm, or unspecified porosity rating. Even though the water names and the filter ratings used to produce these waters are defined inconsistently, the use of 0.2-µm or 0.22-µm filtered Purified Water should be universally acceptable for all applications where Particle-Free Water, Filtered Water, or Ultra-Filtered Water are specified.
过滤水是经过过滤的纯化水，以去除可能干扰分析的颗粒。它有时与无颗粒水和超滤水同义使用，并在一些专著和通论章以及试剂、指示剂和溶液中引用。根据其在USP - NF中的参考位置，它被不同的定义为通过1.2 μ m、0.2 μ m或0.22 μ m过滤器的水，或未指定的孔隙度等级。尽管用于生产这些水的水的名称和过滤器等级的定义不一致，但对于指定无颗粒水、过滤水或超过滤水的所有应用，使用0.2- μ m或0.22- μ m过滤纯化水应该是普遍接受的。
3.3.10HIGH-PURITY WATER
High-Purity Water may be prepared by deionizing previously distilled water and then filtering it through a 0.45-µm rated membrane. This water must have an in-line conductivity of NMT 0.15 µS/cm (NLT 6.67 megohm-cm) at 25°. If the water of this purity contacts the atmosphere even briefly as it is being used or drawn from its purification system, its conductivity will immediately increase by as much as about 1.0 µS/cm ▲at 25°▲ 1S (USP41) as atmospheric carbon dioxide dissolves in the water and equilibrates to hydrogen and bicarbonate ions. Therefore, if the analytical use requires that water conductivity remains as low as possible or the bicarbonate/carbon dioxide levels be as low as possible, the water should be protected from atmospheric exposure. High-Purity Water is used as a reagent, as a solvent for reagent preparation, and for test apparatus cleaning where less stringent water specifications would not be considered acceptable. However, if a user’s routinely available Purified Water is filtered and meets or exceeds the conductivity specifications of High-Purity Water, it could be used in lieu of High-Purity Water.
制备高纯水的方法是将先前的蒸馏水去离子化，然后通过0.45-µm级膜过滤。这种水在25°时的导电性必须为NMT 0.15 μ S/cm (NLT 6.67兆欧厘米)。如果这种纯度的水在使用或从其净化系统中提取时与大气接触哪怕是短暂的，它的导电性将立即增加约1.0 μ S/cm▲，在25°▲1S (USP41)，因为大气中的二氧化碳溶解在水中并平衡为氢和碳酸氢盐离子。因此，如果分析使用要求水的电导率保持尽可能低或碳酸氢盐/二氧化碳水平尽可能低，则应保护水免受大气暴露。当使用高纯水用作试剂，作为试剂制备的溶剂，并用于测试仪器的清洗时，不太严格的水规格标准将被认为是可接受的。但是，如果用户常规可用的纯化水经过过滤，达到或超过高纯水的电导率规格，则可以用它来代替高纯水。
3.3.11DEAERATED WATER
Deaerated Water or “degassed water” is Purified Water that has been treated to reduce the content of dissolved air by “suitable means” such as boiling, sonication, and/or stirring during the application of a partial vacuum, followed by immediate use or protection from air reabsorption.
除气水或“脱气水”是经过处理的纯化水，以减少溶解空气的含量，“适当的方法”，如煮沸，超声波，和/或搅拌，在应用部分真空，然后立即使用或防止空气重吸收。
3.3.12OXYGEN-FREE WATER
Oxygen-Free Water is Purified Water that has been treated to remove or reduce dissolved oxygen. Such treatment could involve deaerating by boiling or sparging with an inert gas such as nitrogen or helium, followed by inert gas blanketing to prevent oxygen reabsorption. Any procedure used for removing oxygen should be verified as reliably producing water that is fit for use.
无氧水是经过处理以去除或减少溶解氧的纯化水。这种处理可能包括通过沸腾或用惰性气体(如氮气或氦气)爆气来除氧，然后用惰性气体覆盖以防止氧的重吸收。任何用于除氧的程序都应被验证为可靠地生产适合使用的水。
3.3.13WATER FOR BACTERIAL ENDOTOXINS TEST
Water for Bacterial Endotoxins Test (BET) is also referred to as Limulus Amebocyte Lysate (LAL) Reagent Water. This type of water is often Water for Injection, which may have been sterilized. It is free from a level of endotoxin that would yield any detectable reaction or interference with the LAL reagent used in the BET (see 85).
细菌内毒素测试(BET)水也被称为鲎试剂(LAL)水。这种水通常是注射用水，可能已经消毒。它不含一定程度的内毒素，不会对BET中使用的LAL试剂产生任何可检测的反应或干扰(见USP 通则 <85>)。
