澄明度检测和澄清度检测的区别

澄明度检测的目的是检测人眼可见到的细小异物（直径50um以上）小白点、小玻璃渣或短小纤维物体。
应用的是“可见异物检查法”。

澄清度检测的目的是把样品和标准浊度液同置于1000lux伞棚灯下观察浑浊状态。
应用的是“浊度检测法”。

从目视成像的方法来说，澄明度看的是样品中目视范围内的最小异物；澄清度看的是样品总体体积的平均浑浊状态。

这是两种概念，一定要加以区分别。

又把细节改进了一些，大家多提意见啊！谁提的意见被采纳，就给谁发红包（100元红包）

在澄清度专用伞棚灯的基础上又开发出了溶液颜色检查专用伞棚灯包括普通用纳氏比色管和小烧杯实验专用的Qz-82a型和凝集反应载玻片专用Qz-82a Plus型

这段时间很多用户提出澄清度检查时样品在0.5以下怎样检查？
0.5以下属高度澄清，目视检查时要注意力集中，眼睛和样品的距离缩短一点，看清楚、眼睛舒服即可。
1.一定要用高透明度的试管（高磷玻璃），不得有气泡和杂质，外壁擦拭干净。
2.更换大号试管(增加试管的直径）即增加液体的厚度。
3.更换石英比色皿。（光线穿透液体的厚度一致）
4.调节旋钮，增大伞棚灯内光强度。
检测人员操作时，头脑中必须要有0.5、1、2、3、4、5号标准浊度液的梯度图像（灰度图像），需经常观察和训练。

通过使用者的反应，用于澄清度检查的高透光试管很不统一，试管的直径，壁厚，材质各式各样，直接影响目视判断结果。以下我们专门开发了《澄清度（浊度）检查专用——石英比浊管》外径19mm，内经17mm，高150mm.

溶液澄清度<中国药典>与<欧洲药典>
溶液澄清度；中国药典：；附录ⅨB澄清度检查法；本法系在室温条件下，将用水稀释至一定浓度的供试品；明、中性硬质玻璃制成)中，在浊度标准液制备5分钟；品种项下规定的“澄清”，系指供试品溶液的澄清度相；超过0.5号浊度标准液；浊度标准贮备液的制备称取于105℃干燥至恒重的硫；量瓶中，加水适量使溶解，必要时可在40℃的水浴中；刻度，摇匀，放置4～6小时；取此溶液与等
附录Ⅸ B澄清度检查法
本法系在室温条件下，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 15～16mm，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，在暗室内垂直同置于伞棚灯下，照度为 1000 lx，从水平方向观察、比较；用以检查溶液的澄清度或其浑浊程度。除另有规定外，供试品溶解后应立即检视。
品种项下规定的“澄清”，系指供试品溶液的澄清度相同于所用溶剂，或未
超过 0.5 号浊度标准液。“几乎澄清”则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。
浊度标准贮备液的制备 称取于105℃干燥至恒重的硫酸肼1.00g，置100ml
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；取此溶液与等容量的 10%乌洛托品溶液混合，摇匀，于 25℃避光静置 24 小时，即得。本液置冷处避光保存，可在两个月内使用，用前摇匀。浊度标准原液的制备 取浊度标准贮备液 15.0ml，置 1000ml 量瓶中，加水
稀释至刻度，摇匀，取适量，置 1cm 吸收池中，照紫外-可见分光光度法(附录Ⅳ A)，在 550nm 的波长处测定，其吸光度应在 0.12～0.15 范围内。本液应在48小时内使用，用前摇匀。 浊度标准液的制备 取浊度标准原液与水，按下表配制，即得。本液应临用
时制备，使用前充分摇匀。
欧洲药典：
Clarity and degree ofopalescence of liquids
VISUAL METHOD一般方法
Using identicaltest-tubes of colourless, transparent, neutral glass with a flat base and aninternal diameter of 15-25 mm, compare the liquid to be examined with areference suspension freshly prepared as described below, the depth of thelayer being 40 mm. Compare the solutions in diffused daylight 5 min afterpreparation of the reference suspension, viewing vertically against a blackbackground. The diffusion of light must be such that reference suspension I canreadily be distinguished from water R, and that reference suspension II canreadily be distinguished from reference suspension I.
在内径15～25mm，平底，无色、透明、中性玻璃管中，加入等量的供试溶液与浊度标准液，使液位的深度都为40mm，按如下所述方法进行比较。浊度标准液制备5分钟后，以色散自然光照射浊度标准溶液和供试溶液，在黑色背景下从垂直方向观察、比较澄清度或
浑浊程度。色散自然光必须较容易区分浊度标准溶液Ⅰ与水，浊度标准溶液Ⅱ与浊度标准溶液Ⅰ
A liquid is consideredclear if its clarity is the same as that of water R or of the solvent used whenexamined under the conditions described above, or if its opalescence is notmore pronounced than that of reference suspension I.
如果供试溶液的澄清、透明程度与水相同，或者与所用溶剂相同，或者其澄清度不超过Ⅰ号浊度标准溶液，那么可判定该溶液为澄清。
Hydrazine sulfatesolution. Dissolve 1.0 g of hydrazine sulfate R in water R and dilute to 100.0mL with the same solvent. Allow to stand for 4-6 h.
硫酸肼溶液：取1.0g硫酸肼溶于水，加水稀释至100.0ml，静置4～6小时。
Hexamethylenetetraminesolution. In a 100 mL ground-glass-stoppered flask, dissolve
2.5 g ofhexamethylenetetramine R in 25.0 mL of water R.
乌洛托品（六亚甲基四胺）溶液 ：在100ml容量瓶中，以25.0ml水溶解2.5g乌洛托品。
Primary opalescentsuspension (formazin suspension).
To theexamethylenetetramine solution in the flask add 25.0 mL of the hydrazinesulfate solution. Mix and allow to stand for 24 h. This suspension is stablefor 2 months, provided it is stored in a glass container free from surfacedefects. The suspension must not adhere to the glass and must be well mixedbefore use.
浊度标准贮备液：在存放乌洛托品溶液的100ml容量瓶中，加25.0ml的硫酸肼溶液。混合，静置24小时，贮存在无表面要求的玻璃容器中，可在2个月内使用。该浊度液不得黏附玻璃，用前必须充分摇匀。
Standard ofopalescence. Dilute 15.0 mL of the primary opalescent suspension to 1000.0 mLwith water R. This suspension is freshly prepared and may be stored for up to24 h.
浊度标准原液：取浊度标准贮备液15ml，加水稀释、定容至1000ml。该液临用前制备，至多保存24小时。
Reference suspensions.Prepare the reference suspensions according to Table 2.2.1.-1. Mix and shakebefore use.
浊度标准液：由浊度标准原液与水按表1-1配制,即得。本液应临用前配制。
Table 1.-1
Turbidity standard.The formazin suspension prepared by mixing equal volumes of the hydrazinesulfate solution and the hexamethylenetetramine solution is defined as a 4000NTU (nephelometric turbidity units) primary reference standard. Referencesuspensions I, II, III and IV have values of 3 NTU, 6 NTU, 18 NTU and 30 NTUrespectively. Stabilised formazin suspensions that can be used to preparestable, diluted turbidity standards are available commercially and may be usedafter comparison with the standards prepared as described.
浊度标准：乳光悬浊贮备液定为4000NTU（比浊测定法的浊度单位）储备液对照标准.浊度标准液I, II, III 和 IV相应的NTU值分别是3 NTU, 6 NTU, 18 NTU 和 30 NTU。稳定的乳光悬浊贮备液可用于稀释制备浊度标准，具有现实的商业价值，也可以与上述的标准化制备进行较。
Formazin has severaldesirable characteristics that make it an excellent turbidity standard. It canbe reproducibly prepared from assayed raw materials. The physicalcharacteristics make it a desirable light-scatter calibration standard. Theformazin polymer consists of chains of different lengths, which fold intorandom configurations. This results in a wide assay of particle shapes andsizes, which analytically fits the possibility of different particle sizes andshapes that are found in the real samples. Due to formazin’s reproducibility,scattering characteristics and traceability, instrument calibration algorithmsand performance criteria are mostly based on this standard.
因福马尔肼具有一些我们所希望的特性，所以它是一种非常优良的浊度标准物。它可以从被测原料中反复制备。具有所想要的光闪射校正标准化的物理特性。福马尔肼聚合物由不同长度的链组成，他们可以折成各种形状，应此可以分析不同大小和形状的粒子。这一特性使得我们可以对现实样品中所具有的不同大小及性状的粒子进行测定。由于。福马尔肼具有可重复性、光散射性、可描绘性、仪器校准可算和操作标准化的特性，使其成为了浊度标准物。
instrumental methods仪器方法简介
Introduction
The degree ofopalescence may also be determined by instrumental measurement of the lightabsorbed or scattered on account of submicroscopic optical densityinhomogeneities of opalescent solutions and suspensions. 2 such techniques arenephelometry and turbidimetry. For turbidity measurement of coloured samples,ratio turbidimetry and nephelometry with ratio selection are used.
该仪器是根据浑浊液和悬浊液亚显微镜光密度的不均一性来测量光的吸收或光的散射，即散射测浊法和透射测浊法。对于有色样品的浊度测试法，要用到比率透射比浊法和可选择比率的散射比浊法。
The light scatteringeffect of suspended particles can be measured by observation of either thetransmitted light (turbidimetry) or the scattered light (nephelometry). Ratio
turbidimetry combinesthe principles of both nephelometry and turbidimetry. Turbidimetry andnephelometry are useful for the measurement of slightly opalescent suspensions.Reference suspensions produced under well-defined conditions must be used. Forquantitative measurements, the construction of calibration curves is essential,since the relationship between the optical properties of the suspension and theconcentration of the dispersed phase is at best semi-empirical.
通过投射光（投射比浊法）或散射光（散射比浊法）来测量混悬粒子的光散射效能。浊度比率结合了透射比浊法和散射比浊法二者的原理。透射比浊法和散射比浊法用于测量具有轻微乳光的混悬液。必须使用在精确的条件下制得的标准混悬液。因为混悬液的光学性质与分散相的浓度之间的关系最多是一个半经验值，所以定量测定主要使用标准曲线法。
The determination ofopalescence of coloured liquids is done with ratio turbidimeters ornephelometers with ratio selection, since colour provides a negativeinterference, attenuating both incident and scattered light and lowering theturbidity value. The effect is so great for even moderately coloured samplesthat conventional nephelometers cannot be used.
因为溶液颜色会产生负干扰，衰减入射光和散射光并降低浊度值，用比率透射浊度法和可选择比率的散射浊度法测定有色溶液的乳光。对于正好适度的有色样品，效果非常好，以至于常规的浊度仪不再使用。
The instrumentalassessment of clarity and opalescence provides a more discriminatory test thatdoes not depend on the visual acuity of the analyst. Numerical results are moreuseful for quality monitoring and process control, especially in stabilitystudies. For example, previous numerical data on stability can be projected todetermine whether a given batch of dosage formulation or active pharmaceuticalingredient will exceed shelf-life limits prior to the expiry date.
用仪器来判断澄清度和乳光，试验所提供的分辨能力更强，不再依靠分析者的视觉敏锐性来判断。对于定性监控和过程控制，特别是稳定性研究，数字化结果更有用。例如，之前所得的关于稳定性的数字化资料用于判断一个给定批号的剂量成分或活性药物组分是否超过了贮存期限或者没过有效期。
Nephelometry
When a suspension isviewed at right angles to the direction of the incident light, the systemappears opalescent due to the reflection of light from the particles of thesuspension (Tyndall effect). A certain portion of the light beam entering aturbid liquid is transmitted, another portion is absorbed and the remainingportion is scattered by the suspended particles. If measurement is made at 90°to the light beam, the light scattered by the suspended particles can be usedfor the determination of their concentration, provided the number and size ofparticles influencing the scattering remain constant. The reference suspensionmust maintain a constant degree of turbidity and the sample and referencesuspensions must be prepared under identical conditions. The Tyndall effectdepends upon both the number of particles and their size. Nephelometricmeasurements are more reliable in low turbidity ranges, where there is a linearrelationship between
nephelometricturbidity unit (NTU) values and relative detector signals. As the degree ofturbidity increases, not all the particles are exposed to the incident lightand the scattered radiation of other particles is hindered on its way to thedetector. The maximum nephelometric values at which reliable measurements canbe made lie in the range of 1750-2000 NTU. Linearity must be demonstrated byconstructing a calibration curve using at least 4 concentrations.
散射比浊法当混悬液在垂直于入射光的方向观察，因混悬液粒子产生的反射，系统出现乳光 (丁达尔效应).。进入一个浑浊液的光束，一部分被透过，一部分被吸收，剩余部分被悬浊粒子散射。如果在与光束90°的方向检测，假如粒子数量和大小对散射的影响维持常数，可以用悬浊粒子的光散射来测定他们的浓度。照溶液的浊度必须保持不变，并且样品和对照混悬液在一样的条件下制备。丁达尔效应)依赖于粒子的大小和数量。在低浊度范围，光散射浊度法更可靠，散射法浊度单位值和有关检测器信号成线性。随浊浊度的增加，不是所有的粒子都能暴露在入射光下的，并且在到达检测器的途径中，其他粒子的散射光被阻碍。一个可靠的测量所能测量的最大散射浊度值是1750-2000 NTU。必须用至少4个浓度构建标准曲线来证明线性。
Turbidimetry
The optical propertyexpressed as turbidity is the interaction between light and suspended particlesin liquid. This is an expression of the optical property that causes light tobe scattered and absorbed rather than transmitted in a straight line throughthe sample. The quantity of solid material in suspension can be determined bythe measurement of the transmitted light. A linear relationship betweenturbidity and concentration is obtained when the particle sizes are uniform andhomogeneous in the suspension. This is true only in very dilute suspensionscontaining small particles. Linearity between turbidity and concentration mustbe established by constructing a calibration curve using at least 4concentrations.
透射浊度法在液体中悬浊粒子和光之间存在相关性，这一光学特性表示为浊度。表示的是光在直线方向上发生的散射和吸收，而不是光直线通过样品的透射光学特性，通过测量透射光来测定混悬液中固体物质的量。当混悬液中粒子的大小均一且性质相同，可获得浊度和浓度之间的线性关系。仅仅在很稀的含有少量粒子的混悬液中，才可实现线性。必须使用至少4个浓度构建标准曲线来证明浊度和浓度间呈线性。
Ratio Turbidimetry
In ratio turbidimetrythe relationship of the transmission measurement to the 90° scattered lightmeasurement is determined. This procedure compensates for the light that isdiminished by the colour of the sample. The influence of the colour of thesample may also be eliminated by using an infrared light-emitting diode (IRLED) at 860 nm as the light source of the instrument. The instrument’sphotodiode detectors receive and measure scattered light at a 90° angle fromthe sample as well as measuring the forward scatter (light reflected) in frontof the sample along with the measurement of light transmitted directly throughthe sample. The measuring results are given in NTU(ratio) and are obtained bycalculating the ratio of the 90° angle scattered light measured to the sum ofthe components of forward scattered and transmitted light values. In ratioturbidimetry the influence of stray light becomes negligible. Nephelometers areused for measurements of
thedegreeofopalescenceof；比率透射比浊法测定的是透视光的测量和90°方向上；Measurementsofreferences；Table2.2.1.-2；INSTRUMENTALDETERMINATIO；乳光的仪器测定；Requirementsinmonographs；乳光的仪器测定在用准确的参比混悬液定义可见方法时；Apparatuthedegree of opalescence of colourless liquids.
比率透射比浊法测定的是透视光的测量和90°方向上散射光的测量之间的关系。这样的操作补偿了因样品颜色引起的光衰减。由样品颜色产生的影响也可以用红外发光二级管进行消除，在860nm处的光作为仪器光源。仪器的光电二级管检测器可以获得并测量在样品90°角方向上的散射光。就像测量朝前的散射光（反射光）一样，即当光直接沿浊被测样品通过，被测样品前方的散射光。测量结果以NTU(比率)给出，并通过计算在90°方向上测得的散射光，和向前的散射光和透射光值之和的比率而获得。在比率透射比浊法中，杂散光的影响变得微乎其微。比浊计用于无色溶液乳光度的测量。
Measurements ofreference suspensions I-IV with a ratio turbidimeter show a linear relationshipbetween the concentrations and measured NTU values (see Table 2.2.1.-2).Reference suspensions I-IV (Ph. Eur.) may be used as calibrators for theinstrument. 用比率浊度计对参比悬浊液I-IV的测量，显示了浓度和测量的NTU值之间的线性关系。参比混悬液I-IV (Ph. Eur.)可以用来校正仪器。
Table 2.2.1.-2
INSTRUMENTALDETERMINATION OF OPALESCENCE
乳光的仪器测定
Requirements inmonographs are expressed in terms of the visual examination method with thedefined reference suspensions. Instrumental methods may also be used fordetermining compliance with monograph requirements once the suitability of theinstrument as described below has been established and calibration withreference suspensions I-IV and with water R or the solvent used has beenperformed.
乳光的仪器测定在用准确的参比混悬液定义可见方法时已表明了要求。一旦后面所规定的建立了仪器的适应性，并用参比混悬液I-IV和水或使用的溶剂进行校正，文中的方法也使用于仪器校正。
Apparatus. Ratioturbidimeters or nephelometers with selectable ratio application use as lightsource a tungsten lamp with spectral sensitivity at about 550 nm operating at afilament colour temperature of 2700 K, or IR LED having an emission maximum at860 nm with a 60 nm spectral bandwidth. Other suitable light sources may alsobe used. Silicon photodiodes and photomultipliers are commonly used asdetectors and record changes in light scattered or transmitted by the sample.The light scattered at 90 ± 2.5° is detected by
the primary detector.Other detectors are those to detect back and forward scatter as well astransmitted light. The instruments used are calibrated against standards ofknown turbidity and are capable of automatic determination of turbidity. Thetest results expressed in NTU units are obtained directly from the instrumentand compared to the specifications in the individual monographs.
仪器：使用可选择的比率浊度计和浊度计时，用钨灯作光源，在2700K的谱线标记温度时，钨灯在大约550nm处有特殊选择性，或者用在860nm处有最大发射并且有60nm光谱宽度的红外发光二级管。也可以使用其他合适的光源。常用硅制光电二极管和光电倍增管作检测器，并记录因样品产生的光散射或光透射的改变。主要检测器检测在90 ± 2.5°方向上的光散射。其他的检测器检测朝后和朝前的光散射，就像测光透射一样。使用的仪器用已知浊度的标准溶液来校正，并能够自动测定浊度。从仪器上直接获得用NTU单位表示的测定结果，并且，在个别文中与规定进行比较。
Instruments complyingwith the following specifications are suitable.
根据后面的说明使用仪器
— Measuring units:NTU. NTU is based on the turbidity of a primary reference standard
of formazin. FTU(Formazin Turbidity Units) or FNU (Formazin Nephelometry Units) are also used,and are equivalent to NTU in low regions (up to 40 NTU). These units are usedin all 3 instrumental methods (nephelometry, turbidimetry and ratioturbidimetry).
— 测量单位：NTU，NTU根据的是福尔马肼标准储备液的浊度。液使用FTU（福尔马肼
浊度单位）或FNU（福尔马肼散射测浊法单位）单位，在低浊度范围内等于NTU（大于40NTU）。这些单位在散射测浊法、浊度法、比率浊度法，三种仪器方法中均可使用。
— Measuring range:0.01-1100 NTU.
— 测量范围：0.01-1100NTU
— Resolution: 0.01 NTUwithin the range of 0-10 NTU, 0.1 NTU within the range of
10-100 NTU, and 1 NTUfor the range > 100 NTU. The instrument is calibrated and controlled withreference standards of formazin.
— 分辨率：在0-10NTU范围内分辨率为0.01NTU，在10-100NTU范围内分辨率为
0.1NTU，在>100NTU范围内分辨率为1NTU。用福尔马肼的参比标准校正和控制仪器。
— Accuracy: 0-10 NTU:± (2 per cent of reading + 0.01) NTU. 10-1000 NTU: ± 5 per
cent.
— 精确度：0-10 NTU±（2%测量读数+0.01）NTU，10-1000NTU: ± 5%
— Repeatability: 0-10NTU: ± 0.01 NTU. 10-1000 NTU: ± 2 per cent of the measured
value.
— 重复性：0-10 NTU± 0.01 NTU，10-1000 NTU± 2%的测量值
— Calibration: with 4reference suspensions of formazin in the range of interest.
Reference suspensionsdescribed in this chapter or suitable reference standards
calibrated against theprimary reference suspensions may be used.
— 校正：用在感兴趣范围内的4中福尔马肼参比混悬液。可以用按本章规定的参比混悬
液或合适的相对于参比混悬液储备液标有刻度的参比标准来校正。
— Stray light: this isa significant source of error in low level turbidimetric measurement;
stray light reachesthe detector of an optical system, but does not come from the sample; < 0.15NTU for the range 0-10 NTU, < 0.5 NTU for the range 10-1000 NTU. — 杂散光：在低水平的浊度测定中，杂散光是主要的误差来源。杂散光就是能到达光学系
统的检测器，但不是由于样品而产生的光。0-10 NTU的范围内杂散光< 0.15 NTU，10-100NTU的范围内杂散光< 0.5 NTU。
Instruments complyingwith the above characteristics and verified using the reference suspensionsdescribed under Visual method may be used instead of visual examination fordetermination of compliance with monograph requirements.
符合上面的特性，并用在可见方法下规定的参比混悬液进行校正的仪器，在这范围内，这些仪器可替代可视检查，这些检查和文中要求一致。
Instruments with rangeor resolution, accuracy and repeatability capabilities other than thosementioned above may be used provided they are sufficiently validated and arecapable for the intended use. The test methodology for the specificsubstance/product to be analysed must also be validated to demonstrate itsanalytical capability. The instrument and methodology should be consistent withthe attributes of the product to be tested.
所提供的仪器的使用范围、分辨率、准确度、重复性、容量及其它上面提到的参数，这些是十分有效的并能够预期使用。对于分析特殊的物质/产品，也必须进行试验方法学验证来说明其分析能力。仪器和方法学应该和测试样品的特性一致。

比浊管在中国药典中的规定是《玻璃管(内径 15～16mm，平底，具塞，以无色、透 明、中性硬质玻璃制成)》；欧洲药典中规定是《在内径15～25mm，平底，无色、透明、中性玻璃管》。
我们对比了中国药典和欧洲药典后来解释一下我公司开发的澄清度专用比浊管，中国药典和欧洲药典都没有对玻璃管的壁厚进行细致的规定（可能和玻璃管加工技术有关），现在我们国内的灯工技术完全可以达到1mm以内，我们综合考虑比浊管的强度和耐用性及造价等几个方面因素，设计成高度为150mm、外径为19mm、内径为17mm的石英材料平底直口比浊管，管壁光滑不得有横纹和纵纹，不得有硬性划伤，壁厚1mm，透光率在95%以上。因管壁1mm薄，所以不能加工成磨口具塞，考虑到标准比浊液中含有酒精易挥发，所以用硅胶塞代替。石英材料在显微镜下的晶格组成要比玻璃晶格组成均匀密实，所以透光性能优于玻璃。

今天和一客户交流时，提到为什么药典要规定澄清度检查，现阶段制药行业中澄清度检查的精度，认真思考后领悟更深。澄清度及浊度检查的方法，影响浊度的主要因数是颗粒度，颗粒的大小（微米级和纳米级）直接影响溶解的时间，样品特别是蛋白、抗体的澄清度检查，所以说澄清度是样品的颗粒大小的表现形式，对溶出度有着重要影响。人的眼睛分辨率大概是5.76亿像素，是非常好的镜头，澄清度检查时高澄清部分2、1、0.5不太好分辨，主要原因是背景和外部环境对人眼睛的干扰，伞棚灯就是把背景和光线处理好，排除环境干扰，可以提高目视的精度标准。