中/美/欧/日四大药典澄清度检查规范 及解决方案

中/美/欧/日四大药典澄清度检查规范-中英双译

中国药典2020

0902 澄清度检查法

澄清度检查法系将药品溶液与规定的浊度标准液相比较，用以检查溶液的澄清度。除另有规定外，应采用第一法进行检测。

品种项下规定的“澄清”，系指供试品溶液的澄清度与所用溶剂相同，或不超过0.5号浊度标准。“几乎澄清”，系指供试品溶液的浊度介于0.5号至1号浊度标准液的浊度之间。

第一法（目视法）

除另有规定外，按各品种项下规定的浓度要求，在室温条件下将用水稀释至一定浓度的供试品溶液与等量的浊度标准液分别置于配对的比浊用玻璃管（内径15-16 mm,平底，具塞，以无色、透明、中性硬质玻璃制成）中，在浊度标准液制备5 分钟后，在暗室内垂直置于伞棚灯下，照度为1000 lx，从水平方向观察、比较。除另有规定外外，供试品溶解后应立即检视。

第一法无法准确判定两者的澄清度差异时，改用第二法进行测定，并以其测定结果进行判定。

浊度标准存贮液的制备 称取于105℃干燥至恒重的硫酸肼1.00 g，置于100 ml量瓶中，加水适量使溶解，必要时可在40℃的水浴中温热溶解，并用水稀释至刻度，摇匀，放置4-6小时；取此溶液于等容量的10%乌洛托品溶液混合，摇匀，于25℃避光静置24小时，即得。该溶液置冷处避光保存，可在2个月内使用，用前摇匀。

浊度标准原液的制备 取浊度标准贮备液15.0 ml，置1000 ml量瓶中，加水稀释至刻度，摇匀，取适量，置1 cm吸收池中，照紫外-可见分光光度法（通则0401），在550 nm的波长处测定，其吸光度在0.12-0.15范围内，该溶液应在48小时内使用，用前摇匀。

浊度标准液制备 取浊度标准原液与水，按照下表配置，即得。浊度标准液应临用时制备，使用前充分摇匀。                                       

第二法（浊度仪法）

供试品的浊度可采用浊度仪测定。溶液中不同大小、不同特性的微粒物质包括有色物质均可使入射光产生散射，通过测定透射光或者散射光的强度，可以检查供试品的浊度。仪器测定模式通常有三种类型，透射光式、散射光式和透射光-散射光比较测量模式（比率浊度模式）。

1.仪器的一般要求

采用散射光式浊度仪时，光源峰值波长为860 nm；测量范围应包含0.01-100NTU。在0-10NTU范围内分辨率应为0.01NTU；在10-100NTU范围内分辨率应为0.1NTU.

2.适用范围及检测原理

本法采用散射光式浊度仪，适用于低、中浊度无色供试品溶液的浊度测定（浊度值为100NTU以下的供试品。）因为高浊度的供试品会造成多次散射现象，时散射光强度迅速下降，导致散射光强度不能正确反映供试品的浊度值。0.5-4号浊度标准液的浊度值范围约为0-40NTU。

采用散射光式浊度仪测定时，入射光和测定的散射光呈90℃夹角，入射光强度和散射光强度关系式如下。

I=K’T I₀

式中 I为散射光强度，单位为cd；

     I₀ 为入射光强度，单位为cd；

     K’为散射系数；

     T为供试品溶液的浊度值，单位为NTU（NTU是基于福尔马肼浊度标准液液测定的散射浊度单位，福尔马肼浊度标准液即为第一法中的浊度标准贮备液）。

在入射光I₀不变的情况下，散射光强度I与浊度值成正比。因此，可以将浊度测量转化为散射光强度的测量。

3.系统的适用性试验

仪器应定期（一般每月一次）对浊度标准液的线性和重复性进行考察，采用0.5号至4号浊度标准液进行浊度值测定，浊度标准液的测定解果（单位NTU）与浓度间应呈线性关系，线性方程的相关系数应不低于0.999；取0.5号至4号浊度标准液，重复测定5次，0.5号和1号浊度标准液测量浊度值的相对标准偏差应不大于5%，2-4号浊度标准液测量浊度值的相对标准偏差不大于2%。

4.测定法

按照仪器说明书要求并采用规定的浊度液进行仪器校正。溶液剂直接取样测定；原料药或者其它剂型按照个论项下的标准规定制备供试品溶液，临用时制备。分别取供试品溶液和相应浊度标准液进行测定，测定前应摇匀，并避免产生气泡，读取浊度值。供试品溶液浊度值不得大于相应浊度标准液的浊度值。

美国药典USP44

<630> VISUAL COMPARISON 视觉比较

The purpose of this test is to provide the details for the visual comparison of the color and/or turbidance of sample solutions of certain concentration to a standard solution or a series of standard solutions of known concentration. Where a color or turbidity comparison is directed, follow the procedures and conditions outlined below for performing these tests.

本试验的目的是提供特定浓度的样品溶液与已知浓度的标准溶液或一系列标准溶液的颜色和/或浊度的视觉比较细节。如果需要进行颜色或浊度比较，请遵循以下程序和条件进行这些测试

Comparison vessels: Color-comparison tubes matched as closely as possible in internal diameter, in depth of sample solution, and in all other respects should be used.

对比容器：应使用内径、样品溶液深度和所有其他方面尽可能匹配的颜色对比管。

Viewing conditions for turbidity comparison: Tubes should be viewed horizontally against a dark background with the aid of a light source directed from the sides of the tubes.

浊度比较的观察条件：应在黑暗背景下，借助从管子侧面发出的光源水平观察管子。

Viewing conditions for color comparison: Tubes should be viewed downward against a white background. Most of the time, common room lighting is sufficient to perform the assessment. A light source directed from beneath the bottoms of the tubes may be used if needed and if the practice is consistent between the materials under comparison.

颜色比较的观察条件：管子应在白色背景下向下观察。大多数情况下，公共空间照明足以进行评估。如果需要，并且对比材料之间的实践一致，可以使用从管底部下方引导的光源

<855> NEPHELOMETRY AND TURBIDIMETRY      散射光浊度法和透射光比浊法

1. INTRODUCTION 介绍

Nephelometry and turbidimetry are analytical techniques that are based on the principles of light-scattering phenomena. Light scattering is the physical phenomenon in which a beam of light changes its direction of propagation (known as deflection) as a result of interaction with sufficiently small matter particles. It has been established from the Maxwell electromagnetic theory that a prerequisite for scattering to occur is that the refractive indexes of the suspended particles must be different from those of the suspending liquid. The larger the difference, the more intense the scattering becomes. There are two types of light scattering: 1) elastic scattering, in which the wavelength of the scattered light and incident light are the same; and 2) inelastic light scattering, in which the wavelength of the scattered light and incident light are different. Only the first type of light scattering (elastic) is relevant to nephelometry and turbidimetry.

散射光浊度法和透射光比浊法是基于光散射现象原理的分析技术。光散射是一种物理现象，其中光束由于与足够小的物质粒子相互作用而改变其传播方向（称为偏转）。根据麦克斯韦电磁理论，散射发生的先决条件是悬浮颗粒的折射率必须不同于悬浮液体的折射率。差异越大，散射越强烈。光散射有两种类型：1）弹性散射，其中散射光和入射光的波长相同；2）非弹性光散射，其中散射光和入射光的波长不同。只有前一种光散射（弹性）与散射光浊度法和透射光比浊法有关。

In turbidimetry, the intensity of the transmitted light is measured and the attenuation of the intensity of incident light as a result of scattering is measured at the direction of incident light (i.e., 0°) and compared to the intensity of incident light (blank measurement). The measured property is an indirect measurement of the scattering effect of the suspended particles and is referred to as turbidance. Any absorbance of light by the suspended sample will result in additional attenuation of light intensity (see Ultraviolet-Visible Spectroscopy <857> and Ultraviolet-Visible Spectroscopy—Theory and Practice <1857>). Hence, it is important to ensure that the material being measured does not absorb light at the measurement wavelength. Indeed the equations governing absorption and turbidimetry are the same (albeit with different values for the attenuation constants). In nephelometric techniques, the intensity of the scattered light at a 90° angle from the propagation direction of the incident light is measured. Therefore, a nephelometric measurement is a direct measurement of the scattering effect of suspended matter.

在透射光比浊法中，测量透射光的强度，并在入射光方向（即0°）测量散射导致的入射光强度的衰减，并与入射光强度进行比较（空白测量）。被测特性是悬浮颗粒散射效应的间接测量，称为浊度。悬浮样品对光的任何吸收都会导致光强度的额外衰减（参见<857> Ultraviolet-Visible Spectroscopy和<1857> Ultraviolet-Visible Spectroscopy—Theory and Practice）。因此，确保被测材料不会吸收测量波长处的光非常重要。实际上，控制吸收和浊度测定的方程式是相同的（尽管衰减常数的值不同）。在散射光浊度法中，测量与入射光传播方向成90°角的散射光强度。因此，散射光浊度法浊度测量是对悬浮物散射效应的直接测量。

2. TERMS AND DEFINITIONS 术语和定义

Terms commonly used in describing turbidimetric and nephelometric techniques are:

• Turbidance (symbol, S): A measure of the decrease of the transmitted incident light beam intensity as a result of the light-scattering effect of suspended particles. The amount of suspended matter may be measured by observation of either the transmitted light (turbidimetry) or the scattered light (nephelometry).

log I₀/I_t = kbc = T

I₀ = intensity of incident light

I_t = intensity of transmitted light

k = molar turbidity coefficient

b = cell path length

c = concentration

T = turbidance

• Turbidity (symbol, τ): In turbidimetric measurements, the turbidity is the measure of the decrease in incident beam intensity/unit length of a given suspension. The International Organization for Standardization defines turbidity as “the reduction of transparency of a liquid caused by the presence of undissolved matter”.

• Turbidity Measurement Units: The turbidity units are stated using a descriptor which indicates the method of measurement.

• Nephelometric Turbidity Units (NTUs): When the turbidity is measured using a nephelometer, which measures the scattered light at a 90° angle from the direction of propagation of incident light, the units of turbidity are called nephelometric turbidity units (NTUs). The magnitude of NTU is defined based on the turbidity generated by primary formazin standard (a suspension made by mixing solutions of hydrazine sulfate and hexamethylenetetramine in water). Safer polymer-bead suspensions are now commercially available and are recognized as an acceptable alternative. However, all those standards are traced to formazin. The primary formazin standard solution has been assigned a turbidity of 4000 NTUs.

Other recognized units for turbidity include the formazin turbidity unit (FTU) and the formazin nephelometric unit (FNU). These units are equivalent to NTU for the range from 0–40 NTUs.

描述浊度法和浊度法的常用术语包括：

•浊度（符号S）：由于悬浮颗粒的光散射效应，透射入射光束强度降低的一种度量。悬浮物的量可以通过观察透射光（比浊法）或散射光（浊度法）来测量。

log I₀/I_t = kbc = T

I₀=入射光强度

I_t=透射光强度

k=摩尔浊度系数

b=样品池路径长度

c=浓度

T=浊度

•浊度（符号，τ）：在透射光浊度测量中，浊度是给定悬浮液的入射光束强度/单位长度减少的量度。国际标准化组织将浊度定义为“由于存在未溶解物质而导致液体透明度降低”。

•浊度测量单位：浑浊度单位用一个描述符表示，该描述符指示测量方法。

•散射光浊度计浊度单位（NTU）：当使用散射光浊度法测量浊度时，浊度计以与入射光传播方向成90°角的角度测量散射光，浊度单位称为散射光浊度法浊度单位（NTU）。NTU的大小是根据初级福尔马肼标准品（一种将硫酸肼和六亚甲基四胺溶液混合在水中制成的悬浮液）产生的浊度定义的。更安全的聚合物微珠悬浮液现已上市，并被公认为可接受的替代品。然而，所有这些标准都可以追溯到福尔马肼。初级福尔马肼标准溶液的浊度为4000 NTU。

其他公认的浊度单位包括福尔马肼比浊法单位（FTU）和福尔马肼浊度法单位（FNU）。这些单位相当于0-40 NTU范围内的NTU。

3. APPLICATIONS 应用

Turbidimetric and nephelometric techniques have applications that include 1) concentration determination of solutions and/or suspensions (determination of several cations and anions by precipitating and suspending the resulting precipitate at well-controlled reaction parameters); 2) measurement of the degree of turbidity of turbid solutions or suspensions; 3) determination of weight-average molecular weights and dimensions of polydisperse systems in the molecular weight range from 1000 to several hundred million; 4) measurement of immunoassays’ reaction kinetics or kinetics of immunoprecipitations (rate nephelometry); 5) monitoring of cell and bacteria growth; and 6) particle size distribution determination of suspended material, particle counting, etc.

透射光比浊法和散射光浊度法技术的应用包括1）溶液和/或悬浮液的浓度测定（通过在控制良好的反应参数下沉淀和悬浮产生的沉淀物，来测定几种阳离子和阴离子）；2）测量混浊溶液或悬浮液的浊度；3）测定分子量在1000到数亿之间的多分散体系的重均分子量和尺寸；4）测量免疫分析的反应动力学或免疫沉淀动力学（比率散射浊度法）；5）监测细胞和细菌的生长；6）悬浮物粒度分布测定、颗粒计数等。

Rate nephelometry is widely used for vaccine components assays and/or quantitation of components in blood serum. It is also used for host cell protein qualification in recombinant biopharmaceuticals. When using the technique, the measurement of the change in the light-scattering response by antigen–antiserum or antigen-purified antibody complexes is used to calculate the amount of antigen (Ag) or antibody (Ab) responsible for the immunological Ab-Ag precipitation reaction or agglutination reaction. Often the antigens under consideration are linked covalently or adsorbed to polymeric microspheres to increase the scattering efficiency; the resulting technique is known as "particle-enhanced immunoassay". Although the technique is described as nephelometry, usually both scattered and transmitted light are measured using the ratio instruments.

比率散射浊度法广泛用于疫苗成分分析和/或血清成分的定量。它还用于重组生物制药中的宿主细胞蛋白质鉴定。当使用该技术时，通过测量抗原-抗血清或抗原纯化抗体复合物的光散射反应的变化，来计算导致免疫抗体-抗原沉淀反应或凝集反应的抗原（Ag）或抗体（Ab）的量。通常考虑抗原共价连接或吸附在聚合物微球上，以提高散射效率；由此产生的技术被称为“颗粒增强免疫分析”。虽然这项技术被称为散射光浊度法，但通常散射光和透射光都是用比率仪器测量的。

Nephelometric measurements are more reliable in low turbidity ranges (relatively low concentration of the scattering medium). In this range, a linear relationship is observed between the sample concentration and the detector’s signal intensity expressed as NTU. As the concentration increases, so does the incidence of multiple scattering that deviates the response from the linearity. The maximum NTU value, which supports a reliable linearity relationship, is in the range of 1750–2000 NTUs. Turbidimetry is preferred for higher turbidity ranges (concentrations of the scattering media). To achieve consistent results, all measurement variables must be carefully controlled. Where such control is possible, extremely dilute suspensions may be measured.

散射光法浊度测量在低浊度范围（散射介质浓度相对较低）更可靠。在该范围内，观察到样品浓度与检测器信号强度（以NTU表示）之间存在线性关系。随着浓度的增加，多次散射的入射角也会增加，从而偏离线性响应。支持可靠线性关系的最大NTU值在1750–2000 NTU范围内。透射光比浊法适用于更高的浊度范围（散射介质的浓度）。为了获得一致的结果，必须仔细控制所有测量变量。在可能的情况下，可以测量极稀的悬浮液。

4. INSTRUMENTATION 仪器仪表

Instruments used for turbidimetric and nephelometric measurements are called turbidimeters and nephelometers, respectively. Generally, these instruments consist of a mercury lamp with filters for the strong green or blue lines, a shutter, a set of neutral filters with known transmittance, and a sensitive photomultiplier, which can be mounted fixed at 0° or at a 90° angle from the incident light propagation direction, or on an arm that can be rotated around the solution cell and set at any angle from −135° to 0° to +135° by a dial outside of the light-tight housing. Solution cells are of various shapes, such as square for measuring 90° scattering; semioctagonal for 45°, 90°, and 135° scattering; and cylindrical for scattering at all angles (see Figure 1).

用于透射光比浊法和散射光浊度法测量的仪器分别称为透射光浊度计和散射光浊度计。通常，这些仪器包括一个带有滤光器的汞灯（用于强绿线或蓝线）、一个快门、一组具有已知透射率的中性滤光器和一个灵敏的光电倍增管，该光电倍增管可安装在与入射光传播方向成0°或90°角的位置，或者在一个臂上，它可以围绕溶液单元旋转，并通过不透光外壳外的表盘设置为−135°到0°到+135°的任何角度。溶液池的形状多种多样，例如用于测量90°散射的正方形；45°、90°和135°散射为半八角形；圆柱形可适用于所有角度的散射（见图1）。

Figure 1. Representative nephelometric (turbidimetric) instrument. Note that Detector 2 may be mounted on a movable arm.

图1。代表性浊度仪。注意，探测器2可安装在可移动臂上。

Turbidity also can be measured with a standard photoelectric filter photometer or spectrophotometer, preferably with illumination in the blue portion of the spectrum. Nephelometric measurements require an instrument with a photocell placed so as to receive scattered, rather than transmitted, light. Because this is the same geometry used in fluorometers, they can be used as nephelometers by proper selection of filters. A ratio turbidimeter combines the technology of 90° nephelometry and turbidimetry. It contains photocells that receive and measure scattered light at a 90° angle from the sample as well as receiving and measuring the forward scatter in front of the sample. It also measures light transmitted directly through the sample. Linearity is attained by calculating the ratio of the 90° angle scattered light measurement to the sum of the forward scattered light measurement and the transmitted light measurement. The benefit of using a ratio turbidimetric system is that the measurement of stray light becomes negligible. In addition, the determination of turbidity of colored suspensions is done exclusively using turbidimetric or nephelometric instruments with ratio mode because this procedure compensates for the attenuation of light as the result of the suspension color. Typically, the light source in these instruments is a tungsten lamp with most of the light intensity at about 550 nm operating at the filament temperature of 2700 K. Other suitable light sources are also available. Typically, the detectors are ▲silicon diodes▲ _{(ERR 1-May-2019)} and photomultipliers. An alternative for eliminating the color effect involves using an infrared light-emitting diode as a light source, which yields an emission maximum centered at about 860 nm and a spectral bandwidth of 60 nm. When laser light sources are also used, especially in nephelometric instruments, the technique is commonly known as "laser nephelometry". The advantage of using laser nephelometers is the significant improvement in signal-to-noise ratio at very low detection levels. Usually the light source is a laser diode with a working wavelength at 660 nm. The high-power density of the laser beam gives rise to higher scattered intensity from smaller particles. Combined with a light trap, which absorbs the unscattered light, the system lowers the stray light significantly. When the use of a nephelometer or turbidimeter is indicated for a procedure in a monograph, instruments working in ratio mode may be used instead.

浊度也可以用标准光电滤光光度计或分光光度计测量，最好是在光谱的蓝色部分进行照明。散射光浊度法测量需要一个装有光电管的仪器，以便接收散射光，而不是透射光。由于这与荧光计中使用的几何结构相同，因此可通过适当选择滤光片将其用作浊度计。比率浊度计结合了90°散射光浊度法和透射光比浊法。它包含光电管，接收和测量与样品成90°角的散射光，以及接收和测量样品前面的前向散射光。它还测量直接穿过样品的光。通过90°角散射光测量值，前向散射光测量值和透射光测量值之和，计算两者的比值，可获得线性度。使用比率浊度测量系统的好处是杂散光的测量变得可以忽略不计。此外，彩色悬浮液的浊度测定仅使用透射光比浊法浊度仪或浊度仪（带比率模式）进行，因为该程序补偿了悬浮液颜色导致的光衰减。通常，这些仪器中的光源是钨灯，在2700 K的灯丝温度下工作，大部分光强约为550 nm。也可使用其他合适的光源。通常，探测器是▲硅二极管▲和光电倍增管。另一种消除颜色效应的方法是使用红外发光二极管作为光源，其最大发射中心约为860 nm，光谱带宽为60 nm。当激光光源也被使用时，尤其是在浊度测量仪器中，这种技术通常被称为“激光浊度测量”。使用激光散射光浊度计的优点是，在非常低的检测水平下，信噪比显著提高。通常光源是工作波长为660 nm的激光二极管。激光束的高功率密度使较小粒子产生更高的散射强度。与吸收未散射光的光阱相结合，该系统可显著降低杂散光。当专著中的某个程序指示使用散射光浊度计或透射光浊度计时，可以使用在比率模式下工作的仪器。

5. FORMAZIN TURBIDITY STANDARDS福尔马肼浊度标准

Formazin is the only known primary turbidity standard. All other standards are secondary and must be traced to formazin. The primary standard is defined in the ▲IUPAC Compendium of Chemical Terminology,▲ (ERR 1-May-2019) 2nd ed. (the Gold Book) as one that is prepared by the user from traceable materials using well-defined methodologies and conditions.

福尔马肼是唯一已知的主要浊度标准。 所有其他标准都是次要的，必须追溯到福尔马肼。 主要标准在▲IUPAC Compendium of Chemical Terminology▲（ERR 1-May-2019）第 2 版（金书）中被定义为由用户使用明确定义的方法和条件从可追溯的材料准备的标准。

Formazin suspension has many features that ensure its suitability as a primary standard. It can be consistently and accurately prepared from reagent-grade starting materials. The suspension consists of random polymers with different lengths and of random configurations, which result in moieties of varying shapes and sizes ranging from less than 0.1 μm to more than 10 μm. Although the polymer chain length distribution has been shown to vary from preparation to preparation, the overall resulting turbidity has been very reproducible.

福尔马肼悬浮液有许多特点，以确保其适合作为主要标准。它可以从试剂级的起始材料中始终如一、准确地制备。该悬浮液由不同长度和随机构型的聚合物组成，其组成的聚合物的形状和尺寸从小于0.1 μm到大于10 μm不等。尽管聚合物链长分布已被证明因制备而异，但总的浊度结果是可以很好地重现的。

5.1 Preparation of the Formazin Standards 福尔马肼标准液的制备

[NOTE—All procedures described below must be performed at 20 ± 2° (see Volumetric Apparatus <31>.]

• Hydrazine sulfate solution: Dissolve 1.000 g of ACS grade hydrazine sulfate (N₂H₄·H₂SO₄) in particle-free water in a 100-mL Class A volumetric flask and dilute with particle-free water to volume. Allow this solution to stand for 4–6 h.

•Primary formazin standard: Dissolve 2.50 g of analytical grade hexamethylenetetramine [(CH₂)₆N₄] in 25.0 mL of particle-free water in a 100-mL flask. Add 25.0 mL of hydrazine sulfate solution using a Class A 25-mL “to deliver” pipette and mix thoroughly. Allow the preparation to stand for 48 h at 25 ± 1° before using. The resulting suspension is stable for 2 months.

•Formazin stock standard suspension 1: Using a 15-mL Class A “to deliver” pipette, transfer 15 mL of the Primary formazin standard to a 1-L volumetric flask, and dilute with particle-free water to volume and mix. The resulting suspension has a turbidity of 60 NTU.

• Formazin stock standard suspension 2: Using a 50-mL Class A “to deliver” pipette, transfer 50 mL of Primary formazin standard to a 200-mL volumetric flask, and dilute with particle-free water to volume and mix. The resulting suspension has a turbidity of 1000 NTUs.

• Formazin reference suspensions: Prepare by mixing in a 100-mL volumetric flask, portions of the respective Formazin stock standard suspension and particle-free water according to Table 1.

[注：以下所有的程序必须在20±2°的条件下进行（参见<31 Volumetric Apparatus >）]

•硫酸肼溶液：将1.000 g ACS级硫酸肼（N₂H₄·H₂SO₄）溶解在100 mL 的A类容量瓶中中，并用无颗粒水稀释至刻度。让该溶液静置4-6小时。

•初级福尔马肼标准液：将2.50 g分析级六亚甲基四胺[(CH₂)₆N₄]溶于25.0 mL无颗粒水中，装入100 mL烧瓶。使用A级25ml移液管加入25.0 mL硫酸肼溶液，并充分混合。使用前，让制剂在25±1°的温度下静置48小时。由此产生的悬浮液可稳定运行2个月。

•福尔马肼储备标准悬浮液1：使用15 mL A类移液管，将15 mL福尔马肼初级标准液转移至1 L容量瓶中，并用无颗粒水稀释至刻度并混合。所得悬浮液的浊度为60 NTU。

•福尔马肼储备标准悬浮液2：使用50 mL A类移液管，将50 mL福尔马肼初级标准液转移至200 mL容量瓶中，并用无颗粒水稀释至刻度并混合。所得悬浮液的浊度为1000 NTU。

•福尔马肼参考悬浮液：根据表1，在100 mL容量瓶中混合各份福尔马肼储备标准悬浮液和无颗粒水，制备福尔马肼参考悬浮液。

6. QUALIFICATION OF TURBIDIMETERS AND NEPHELOMETERS 透射光式浊度仪与散射光式浊度仪的鉴定

The suitability of a specific instrument for a given procedure is ensured by a stepwise life cycle evaluation for the desired application from selection to instrument retirement. The qualification comprises three components: 1) installation qualification (IQ), 2) operational qualification (OQ), and 3) performance qualification (PQ) (see Analytical Instrument Qualification <1058>).

特定仪器对给定程序的适用性由从选择到仪器报废的预期应用的逐步生命周期评估来确保。鉴定包括三个部分：1）安装鉴定（IQ）、2）操作鉴定（OQ）和3）性能鉴定（PQ）（参见<1058>Analytical Instrument Qualification章节）。

The purpose of this section is to provide test methods and acceptance criteria to ensure that the instrument is suitable for its intended use (OQ), and that it will continue to function properly over extended time periods (PQ). As with any spectrometric device, a turbidimetric and nephelometric spectrometer must be qualified for both wavelength (x-axis, if not fixed) and photometric (y-axis, or signal axis) accuracy and precision, and meet the requirements for the stray light. OQ is carried out across the operational ranges required within the laboratory for both the absorbance and wavelength scales.

本节的目的是提供测试方法和验收标准，以确保仪器适合其预期用途（OQ），并在延长的时间段（PQ）内继续正常工作。与任何光谱仪一样，透射光式和散射光式浊度光谱仪必须具备波长（x轴，如果不固定）和光度（y轴或信号轴）的准确度及精度，并满足杂散光的要求。OQ是在实验室内吸光度和波长标度所需的操作范围内进行的。

Acceptance criteria for critical instrument parameters that establish “fitness for purpose” are verified during IQ and OQ. Specifications for particular instruments and applications can vary depending on the analytical procedure used and the desired accuracy of the final result. Instrument vendors often have samples and test parameters available as part of the IQ/OQ package.

在IQ和OQ期间，验证确定“用途适用性”的关键仪器参数的验收标准。特定仪器和应用的规格可能因使用的分析程序和最终结果的预期准确度而异。仪器供应商通常将样品和测试参数作为IQ/OQ包的一部分提供。

Wherever possible in the procedures detailed as follows, primary reference standards or certified reference materials (CRMs) are to be used. Formazin is the only primary reference standard used in turbidimetry and nephelometry. All the other standards, including the CRMs, must be correlated to formazin. The CRMs should be obtained from a recognized accredited source and include independently verified traceable value assignments with associated calculated uncertainty. CRMs must be kept clean and free from dust. Recertification should be performed periodically to maintain the validity of the certification.

在以下详述的程序中，应尽可能使用主要参考标准或认证参考材料（CRM）。福尔马肼是比浊法法和浊度法中唯一使用的主要参考标准。所有其他标准，包括CRM，必须与福尔马肼相关。CRM应从认可的认证来源获得，并包括独立验证的可追溯值分配及相关的计算不确定性。CRM必须保持清洁，无灰尘。应定期进行重新认证，以保持认证的有效性。

6.1 Calibration校准

All of the turbidimetric and nephelometric instruments are calibrated against standards of known turbidity. The instrument must be calibrated using formazin turbidity standards prior to its first time use and at least every 3 months or as specified by t