11 USP REFERENCE STANDARDS美国药典对照标准品
INTRODUCTION
Reference Standards provided by the United States Pharmacopeial Convention (USP Reference Standards or USP RS) are highly characterized materials demonstrated to have the appropriate qualities to support their intended use. USP RS are not for use in humans or animals.
美国药典公约(USP参考标准品或USP RS)提供的参考标准是高度特征性的材料，证明具有支持其预期用途的适当质量。USP RS不适用于人类或动物。
USP RS are generally linked to relevant tests and assays in the United States Pharmacopeia (USP) or National Formulary (NF) documentary standards. They have been approved and established as suitable for use in the context of these applications. When approved as suitable for use in USP or NF tests and assays, USP RS also assume official status and legal recognition in the United States and other jurisdictions that recognize the USP or NF (see General Notices, 2.30 Legal Recognition). Where USP or NF tests or assays call for the use of a USP RS, only those results obtained using the specified USP RS are conclusive (see General Notices,5.80 USP Reference Standards).
USP RS通常与美国药典(USP)或国家处方(NF)文件标准中的相关测试和测定相关联。它们已被批准并确定适合在这些应用程序中使用。当批准适用于USP或NF测试和测定时，USP RS还在美国和承认USP或NF的其他司法管辖区具有官方地位和法律认可(见凡例，2.30法律认可)。当USP或NF试验或测定要求使用USP RS时，只有使用指定的USP RS获得的结果是结论性的(见凡例，5.80USP参考标准品)。
USP RS may also be used to support other measurements not necessarily prescribed in USP–NF. Assessment of the suitability for use in other applications is the responsibility of the user.
USP RS也可用于支持USP-NF中不一定规定的其他测量方法。在其他应用程序中使用的适用性评估是用户的责任。
ESTABLISHMENT APPROACHES AND VALUE ASSIGNMENT
USP RS, when they are physical materials, are Reference Materials as defined in the International Vocabulary of Metrology— Basic and General Concepts and Associated Terms (VIM). The value assigned to quantitative standards relies on a mass determination by a primary reference measurement procedure such as a mass balance determination. If the value has been assigned by using a primary reference measurement procedure, the USP RS in metrology terms can be considered a primary measurement standard. If the value has been assigned by comparison or calibration to another material, the USP RS should be considered a secondary measurement standard; for example, when appropriate, USP RS are calibrated relative to international reference materials such as those provided by the World Health Organization (WHO).
USP RS，当它们是物理材料时，是国际计量词汇-基本和一般概念及相关术语(VIM)中定义的参考材料。赋予定量标准的值依赖于通过主要参考测量程序(例如质量平衡测定)进行的质量测定。如果该值是通过使用主要参考测量程序赋值的，则USP RS在计量术语中可被视为主要测量标准。如果该值是通过对另一种材料的比较或校准而确定的，USP RS应被视为第二个测量标准;例如，在适当情况下，USP RS相对于世界卫生组织(世卫组织)提供的国际参考物质进行校准。
USP may choose to develop USP RS that follow the requirements for the development of Certified Reference Materials (CRMs) in accordance with the relevant International Organization for Standardization (ISO) Guides. Correct use of these CRMs support traceability of results to SI units and comparability of procedures. USP may also provide RS that are traceable to a CRM established by a National Metrology Institute or other official provider as required or referenced by the documentary standard.
USP可以根据相关的国际标准化组织(ISO)指南，选择开发符合标准物质(CRMs)开发要求的USP RS。正确使用这些标准关系到支持结果到SI单位的溯源和程序的可比性。USP还可以提供可追溯至国家计量研究所或其他官方供应商建立的CRM的RS(根据要求或文件标准的引用)。
USP may issue USP RS that are not required in a documentary standard. The material and performance attributes for these USP RS are described in the supporting documentation supplied with the USP RS.
USP可以发布文件标准中不要求的USP RS。这些USP RS的材料和性能属性在随USP RS提供的支持文档中进行了描述。
USP RS go through a rigorous characterization as part of their establishment process. The types and extent of testing (including the number of laboratories) are primarily driven by the official uses of the standard, but material characterization goes beyond the establishment of suitability for use. Typically, a comparison to the previous lot is performed during the study when establishing a replacement lot of a USP RS as an additional verification of the suitability of the new standard lot.
USP RS通过严格的鉴定作为建立过程的一部分。测试的类型和程度(包括实验室的数量)主要是由标准的官方用途决定的，但材料的表征超出了确定是否适合使用的范围。通常，在建立USP RS替代批次作为新标准批次适用性的额外验证时，要与前一批进行比较。
USP REFERENCE STANDARDS FOR USP OR NF
Official applications of USP RS are specified in USP or NF monographs and general chapters. These applications are as follows.
Some USP RS could be used for several types of applications listed below.
USP RS的正式应用在USP或NF专著和通则中有详细说明。这些应用如下。一些USP RS可用于下面列出的几种类型的应用。
1.Quantitative determinations定量测定
A.The majority of USP RS for quantitative determinations support measurements for total amounts of material on a mass basis. This category includes USP RS for USP or NF articles and impurity standards labeled for quantitative use. The assigned value of the USP RS is stated on the labeling and should be included in calculations used in the monograph and applicable general chapters.
大多数用于定量测定的USP RS支持以质量为基础的材料总量的测量。此类别包括USP RS(用于USP或NF制品)和标记为定量使用的杂质标准。USP RS的指定值应在标签上注明，并应包括在专著和适用的通则中使用的计算中。
B.USP RS for relative determinations of potency or activity are often required for the measurement of complex materials (e.g., biologics, antibiotics, herbals, some dietary supplements) and quantitative amounts may be expressed in units or relative potency terms other than mass.
对于复杂物质(例如，生物制品、抗生素、草药、某些膳食补充剂)的测量，通常需要USP RS的相对效价或活性测定，定量量可以用单位（units）或相对效价来表示，而不是质量。
These USP RS are established by calibration to a primary standard where the property of the material determines the unit. For these standards where an International Standard (IS) established by the WHO exist, USP RS are National Measurement Standards. The USP RS documentation will indicate when the USP RS has been established by comparison to an International Standard (IS) established by the WHO. Results may be expressed in USP Units, Units, or International Units. Additional statements about unit/mass relationship, specific activity, or other relevant information related to the measurement may be provided in the USP RS documentation.
这些USP RS是通过对主要标准的校准建立的，其中材料的性质决定了单位（unit）。对于这些由WHO建立的国际标准(IS)， USP RS是国家测量标准。USP RS文件将通过与WHO制定的国际标准(IS)的比较表明USP RS何时制定。结果可以用USP单位、单位或国际单位表示。关于单位/质量关系、比活度或与测量相关的其他相关信息的其他声明可在USP RS文件中提供。
For antibiotics that use microbial assays to determine activity, the potency is determined in units or micrograms per milligram (µg/mg) of activity. The units or µg/mg of activity is established against a WHO IS when one exists for that antibiotic. Where no WHO IS is presently available, USP establishes and maintains the standard to which USP RS lots are calibrated. This approach may also be chosen for other complex materials for which no WHO IS exists. In these instances, the USP standard is established in such a way as to ensure long-term stability and fitness for purpose, which permits the calibration of successive lots of USP RS with increased confidence that drift in the assigned unit can be avoided.
对于使用微生物测定法测定抗生素的活性，效力以活性单位或微克/毫克(µg/mg)确定。当存在针对某一抗生素的WHO IS时，确定其活性单位或µg/mg。在目前没有WHO IS可用的情况下，USP建立并维持USP RS批号校准的标准。这种方法也可用于不存在世卫组织信息系统的其他复杂材料。在这些情况下，USP标准以确保长期稳定和适合的方式建立，这允许校准连续批次的USP RS，以增加信心，漂移的指定单位可以避免。
2.Qualitative determinations定性测定
A.Identification USP RS: USP RS for identification tests are typically presented as single components of high chemical purity, but may also be complex materials of natural, synthetic, or recombinant origin (e.g., biologics, natural products, botanicals, complex nonbiologicals, others). For complex materials, the identification attributes are presented in a matrix of other materials and require highly specific measurement systems (e.g., nucleic acid-based identity determination for naturally derived materials).
鉴定USP RS:鉴定测试的USP RS通常表现为高化学纯度的单一成分，但也可能是天然、合成或重组来源的复杂材料(例如，生物制品、天然产品、植物制品、复杂的非生物制品、其他)。对于复杂的材料，识别属性以其他材料的模型表示，并需要高度特异的测量系统(例如，基于核酸的天然衍生材料的鉴定测定)。
B.Impurity USP RS: Impurity USP RS are typically used for system suitability or as impurity markers. They may be presented as single-component materials, as mixtures containing more than one impurity, or as drug substance(s) containing one or more impurities.
杂质USP RS:杂质USP RS通常用于系统适用性或作为杂质标记。它们可以表现为单组分材料、含有一种以上杂质的混合物或含有一种或多种杂质的原液。
C.Digital and Visual USP RS: Unlike chemical reference materials, these USP RS are not physical materials used in chemical analyses. Instead, these visual images are used by analysts to compare test articles to ensure that they meet compendial requirements
数字和视觉USP RS:与化学参考材料不同，这些USP RS不是用于化学分析的物理材料。相反，分析人员使用这些可视化图像来比较测试材料，以确保它们满足药典需求
3.Performance verification. These USP RS are typically called for in general tests and assays and are provided to analyze and, where appropriate, to facilitate adjustment of the operation of an instrument to ensure the results obtained are accurate and/or precise or otherwise give acceptable results. The use of these USP RS is generally described in associated general chapters and in the supporting documentation supplied with the USP RS.
性能核查。这些USP RS通常用于一般的测试和分析，并用于分析和在适当的情况下，便于调整仪器的操作，以确保获得的结果是准确和/或精确的，或以其他方式给出可接受的结果。USP RS的使用通常在相关的通论章和随USP RS提供的支持文档中描述。
USP REFERENCE STANDARDS FOR OTHER MEASUREMENTS AND DETERMINATIONS
USP also develops Reference Standards that may not be required in official USP–NF tests or assays. USP provides RS specified in the current edition of the Food Chemicals Codex, the Herbal Medicines Compendium, and standards referenced in regulatory requirements.
USP还开发了官方USP - NF测试或分析中可能不需要的参考标准。USP提供了当前版本的食品化学品法典、草药简编和法规要求中引用的标准中指定的RS。
USP RS without an official use in the USP–NF are developed following the same quality systems used for the characterization and release of USP RS used in official tests and assays. These USP RS are generally intended to address common quality issues and challenges inherent to technologies that cut across different types of products (e.g., system suitability samples, calibrators used to demonstrate performance of an analytical procedure, process, or equipment). Extensive characterization of the USP RS candidate is required and the testing plan takes into account the use of different methods to measure the same attribute, demonstrating broader applicability of these standards. In the absence of a companion monograph or chapter, the information generated from these studies may be disseminated to the user via other types of supporting documents including but not limited to the USP Certificate.
USP RS在USP -NF中没有正式使用，它是按照USP RS在官方测试和分析中用于表征和发布的相同质量系统开发的。这些USP RS通常旨在解决常见的质量问题和固有的技术挑战，跨越不同类型的产品(例如，系统适用性样品，用于演示分析程序、过程或设备的性能的校准品)。需要对USP RS候选产品进行广泛的描述，测试计划考虑到使用不同的方法来测量相同的属性，表明这些标准具有更广泛的适用性。在没有配套的专著或章节的情况下，这些研究产生的信息可以通过其他类型的支持文件传播给用户，包括但不限于USP证书。
LABELING
The labeling material consists of the label affixed to the USP RS and the associated USP Certificate. Both must be reviewed prior to handling or using the USP RS because in some cases not all of the necessary information can fit on the affixed label. USP Certificates are lot specific and are publicly available on the USP website (www.usp.org). Additional documentation may be provided with the USP RS as needed.
标签材料包括贴在USP RS上的标签和相关的USP证书。在处理或使用USP RS之前，两者都必须进行审查，因为在某些情况下，并不是所有必要的信息都能贴到标签上。USP证书有很多具体的内容，可以在USP网站(www.usp.org)上公开获取。根据需要，USP RS可提供额外的文件。
The affixed USP RS label typically contains the RS name, catalog number, lot number, package size, assigned value, storage conditions, handling instructions, and country of origin information. For multi-component items, there is also an outer package and label.
粘贴的USP RS标签通常包含RS名称、目录编号、批号、包装尺寸、分配值、存储条件、处理说明和原产国信息。对于多组件的物品，也有一个外包装和标签。
The affixed label also includes hazard and precautionary statements required by the Occupational Safety and Health Administration (OSHA) under the current revision of the Hazard Communication Standard (29 CFR 1910.1200). Terms used in these statements do not necessarily reflect specific definitions in the USP–NF. Safety Data Sheets for all USP RS are publicly available on the USP website (www.usp.org).
附加标签还包括职业安全与健康管理局(OSHA)根据当前修订的危险沟通标准(29 CFR 1910.1200)要求的危险和预防说明。这些语句中使用的术语不一定反映USP-NF中的特定定义。所有USP RS的安全数据表可在USP网站(www.usp.org)上公开获取。
In addition to the information provided on the affixed USP RS label, the USP Certificate will generally contain the RS chemical name and structure, sequence (if applicable), CAS number, molecular formula, and molecular weight. A typical chromatogram may also be included if necessary for the intended use. Additional information may be included such as special handling instructions or information needed for the use of the USP RS. The USP Certificate also includes a copy of the label text and a series of general instructions.
除了贴在USP RS标签上的信息外，USP证书通常还包括RS化学名称和结构、序列(如果适用)、CAS号、分子式和分子量。如有必要，也可包括典型色谱图用于预期用途。附加信息可能包括特殊处理说明或使用USP RS所需的信息。USP证书还包括标签文本的副本和一系列一般说明。
PACKAGING
The amount of material per individual USP RS container depends on the application of the standard. Some standards (mainly materials with significant handling requirements or materials that are available only in small amounts) are provided in single-use containers. Some single-use products may be lyophilized with content labeled in mass or activity units per container. If so labeled, the content of the container must be reconstituted in its entirety without any additional weighing. Instructions for use are given either on the label or USP Certificate, or in the monographs where the standard is used.
每个USP RS容器的材料量取决于标准的应用。一些标准(主要是有重大处理要求的材料或只有少量可用的材料)是用一次性容器提供的。一些一次性使用的产品可以冻干，每个容器以质量或活性单位标注内容。如果有这样的标记，容器的内容物必须在不增加任何重量的情况下完整地重新组合。使用说明可以在标签或USP证书上给出，也可以在使用该标准的专著中给出。
STORAGE
USP RS should be stored in the packaging configuration provided by USP, according to the label and USP Certificate instructions. When storage in refrigerator or freezer is stated on the label, follow the definitions given in Packaging and Storage Requirements 659. If no specific directions or limitations are provided on the label, the conditions of storage shall be room temperature and protection from moisture, light, freezing, and excessive heat.
USP RS应根据标签和USP证书说明存储在USP提供的包装配置中。如果标签上注明了储存在冰箱或冰柜中，请遵循包装和储存要求(659)中给出的定义。如果标签上没有明确的说明或限制，储存条件应是室温，并防止潮湿、光照、冻结和过热。
Any unused portions remaining after the container has been opened should be carefully stored in accordance with the user’s Standard Operating Procedures and good laboratory practices. Decisions concerning the proper use of previously opened USP RS are the responsibility of the user, unless otherwise specified on the labeling. The user is responsible for ensuring that the contents of opened vials continue to be suitable for their intended use.
容器打开后剩余的任何未使用的部分应按照用户的标准操作程序和良好的实验室操作规范仔细储存。关于正确使用先前打开的USP RS的决定是用户的责任，除非标签上另有规定。用户有责任确保打开的小瓶内的内容物继续适合其预期用途。
CONTINUED SUITABILITY FOR USE
All USP RS are periodically reevaluated by USP throughout their lifecycles. The USP Continued Suitability for Use (CSU) program is designed to monitor real-time suitability for use of all current lots of USP RS. Suitability testing intervals are established based on collaborative study data, manufacturer or supplier data, testing results, and CSU data trending and projections. When and where applicable, an accelerated degradation study may be performed to provide additional information on the stability of the USP RS and to support suitability testing intervals. The goal of the CSU program is to confirm the continued suitability of the material for use of a USP RS in its compendial applications during its valid use period.
所有USP RS在其生命周期内由USP定期重新评估。USP持续使用适宜性(CSU)计划旨在实时监测当前所有批次USP RS的使用适宜性。适宜性测试间隔是根据合作研究数据、制造商或供应商数据、测试结果以及CSU数据趋势和预测建立的。当适用时，可进行加速降解研究，以提供关于USP RS稳定性的额外信息，并支持适宜性测试间隔。CSU计划的目标是确认USP RS材料在其有效使用期间在其药典应用中的持续适用性。
VALID USE DATE
USP RS lots are assigned a valid use date upon depletion. The valid use date is the last day upon which a particular lot of USP RS can be used. Typically, the valid use date assigned is one year from the date the last vial of a lot is sold.
USP RS批在耗尽时分配有效使用日期。有效使用日期是某批USP RS可以使用的最后一天。通常情况下，指定的有效使用日期是从最后一个小瓶出售的日期起一年。
It is the responsibility of the user to ascertain that a particular lot of a USP RS has official status either as a “Current Lot” or as a “Previous Lot” prior to the valid use date. Current and previous lot information, as well as the most current version of the catalog, can be found on the USP website (www.usp.org).
用户有责任确定USP RS的特定批次在有效使用日期之前具有“当前批次”或“以前批次”的可用状态。当前和以前的批号信息，以及最新版本的目录，可以在USP网站(www.usp.org)上找到。
PROPER USE
Many compendial tests and assays are based on comparison of a sample to a USP RS. In such cases, measurements are made on preparations of both the sample and the USP RS. Where it is directed that a standard solution or a standard preparation be prepared for a quantitative determination, it is intended that the USP RS substance be accurately weighed (see Balances 41) and subsequent dilutions be performed using volumetric apparatuses with, at least, the prescribed tolerances (see Volumetric Apparatus 31). Potential errors associated with the use of volumetric apparatus of small volume should be taken into account (see also General Notices, 6.50.20.1 Adjustments to Solutions).
许多药典试验和测定是基于样品与USP RS的比较。在这种情况下，对样品和USP RS的制剂进行测量。如果要求制备标准溶液或标准制剂用于定量测定，则需要对USP RS物质进行准确称量(见天平41)，并且使用容量仪器进行后续稀释，至少使用规定的公差(参见容积仪器31)。应考虑到与使用小体积的容积仪器有关的潜在误差(另见凡例，6.50.20.1溶液的调整)。
Whenever the labeled directions for use require either drying or a correction for water and/or volatiles, this should be performed at the time of use. Further experimental details should be controlled by the user’s Standard Operating Procedures and good laboratory practices.
当标签上的使用说明要求干燥或对水和/或挥发物进行校正时，应在使用时进行。进一步的实验细节应由用户的标准操作程序和良好的实验室实践控制。
The following list of label terms and definitions is provided as guidance for the handling and use of USP RS:
提供以下标签术语和定义列表，作为处理和使用USP RS的指导:
•Assigned Value (Calculation Value): The quantity value assigned to a USP RS for its use in the quantitative compendial applications.
分配值(计算值):分配给USP RS用于定量药典应用的数量值。
•As Is: Use the USP RS as received, without drying or additional testing and apply the assigned value to correct the concentration of the standard solution and/or preparation. This is the preferred option, and is selected whenever data indicate the moisture content is constant over time. For the USP RS to be used on the as is basis, the assigned value has already been corrected for volatiles, including moisture.
原样:使用收到的USP RS，无需干燥或额外测试，并应用指定值来校正标准溶液和/或制剂的浓度。这是首选的选择，当数据表明水分含量随着时间的推移是恒定的时，就选择这一方法。对于USP RS作为基准使用，已对挥发性物质(包括水分)的指定值进行了校正。
•Anhydrous Basis, Determine Water Content Titrimetrically at Time of Use: Use the USP RS as received, and apply the water content determined to correct the weight of the standard. After the correction for water is applied, use the assigned value to correct the concentration of the standard solution and/or preparation. At the time a USP RS is to be weighed, proceed as directed under Water Determination 921, Method I, and determine the water content on a separate portion of material. Instrumental or microanalytical methods are acceptable for this purpose. When using typical amounts (about 50 mg of the USP RS), titrate with a 2- to 5-fold dilution of the reagent.
以无水物计，使用时滴定测定水含量: 使用USP RS收到，并应用测定的水含量校正标准的重量。在对水进行校正后，使用指定值来校正标准溶液和/或制剂的浓度。在对USP RS称量时，按照水测定921方法I的指导进行，并测定材料的单独部分上的水含量。仪器或微量分析方法可用于此目的。当使用典型量(约50 mg USP RS)时，滴定2- 5倍稀释的试剂。
•Dried Basis, Determine Loss on Drying at Time of Use: Use the USP RS as received, and apply the loss on drying value obtained to correct the weight of the standard. After the correction for loss on drying is applied, use the assigned value to correct the concentration of the standard solution and/or preparation. Determine the loss on drying value on a separate portion of material, following the monograph procedure under Loss on Drying. Sample sizes smaller than those required in the general test chapter may be used for a USP RS provided that the user can obtain a sufficiently accurate result.
以干燥品计，使用时折干:使用收到的USP RS，并应用损失的干燥值，以纠正重量的标准。在对干燥的损失进行校正后，使用指定值来校正标准溶液和/或制剂的浓度。确定损失的干燥值在一个单独的部分的材料，遵循各论程序下的干失测定方法。折干不是干燥后使用。如果用户能够获得足够准确的结果，则小于通则章节中要求的样本量的情形可用于USP RS。
•Dried Material, Dry Before Use, or Use Previously Dried Material: Dry the USP RS before use. Use immediately after drying under stated conditions. Drying should not be performed in the original container. A portion of the material should be transferred to a separate drying vessel. Apply the assigned value to correct the concentration of the standard solution and/or preparation prepared with the dried USP RS.
干燥材料，使用前干燥，或使用之前干燥的材料:使用前干燥USP RS。在规定条件下干燥后立即使用。干燥不应在原容器中进行。一部分物料应转移到单独的干燥容器中。应用指定值来校正用干燥USP RS配制的标准溶液和/或制剂的浓度。
