主题：【讨论】如何按照欧盟2002/657/EC计算检测限（CCα）和定量限(CCβ)

这个要看你的研究的具体要求了。比如我们主要研究在美国上市的药物，那么我们要符合FDA的要求，对于欧盟的就不管他。另外在质谱中定量限的信噪比一般要求大于5即可，好像没有硬性要求大于10.

药物分析中对于药物的检测限、定量限我们国家一般是参考国外的法规，比如欧盟或者美国。我这里专门说的是欧盟发布的2002/657/EC中所提到的检测限（CCα）和定量限(CCβ)计算方法。

转载自http://www.antpedia.com/  板油aa_tang

对于食品安全、药物残留检测领域，偶属外行，但自己也做了n年色谱质谱分析（n>3，^_^），基于LZ的问题，探讨一下偶个人对定量分析方法学验证方面的粗浅认识。

（定性）定量分析，都必须得有方法学考察，即对所采用的分析方法进行验证，以充分表明分析方法符合检测项目的目的和要求！验证内容包括方法的专属性、线性、范围、准确度、精密度、检测限、定量限、耐用性和系统适用性等。LZ在这里讨论的是检测限（LOD）和定量限（LOQ），且是信噪比法！

其实，在ICH Q2B文件里罗列了三种方法：
(LOD=检测限，LOQ=定量限）
1. 肉眼观测 (用此方法报告LOD或LOQ时要附上色谱图）
2. S/N (LOD = 3, LOQ =10)
3. LOD = 3.3*standard deviation/slope, LOQ = 10*standard deviation/slope

所以，采用信噪比法来计算检测限（CCα）和定量限(CCβ)是没有任何问题的，完全可行！

而MRPL，即Minimum Required Performance Limit首字母缩写，通常所说的欧盟制定的最低残留限量就是指这个，说白了，贸易壁垒/技术壁垒！
“The MRPL represents the minimal concentration of the banned substance in question that must be able to determine with specified degrees of accuracy and precision by an analytical method and is based on the current limit of detection (LOD).”
——来源http://www.coextra.eu/news/news1257.html

同时， 欧盟官方指南文件（EUROPEAN COMMISSION，HEALTH & CONSUMER PROTECTION DIRECTORATE-GENERAL  GUIDELINES FOR THE IMPLEMENTATION OF DECISION 2002/657/EC）上明确说明：
      “ It should be noted that the minimum required performance level is not the MRPL. The minimum required performance level is the lowest concentration of analyte which is expected to be detected (screening methods) or its identity unequivocally confirmed (confirmatory methods). It follows that for substances for which an MRPL has been proposed, the minimum required performance level should be less than the MRPL.
      It is therefore recommended that representative blank material must be used, which is fortified at and above the minimum required performance level. The lowest calibration point is that at which the method starts to detect or identify the analyte. (This does not mean that the method should detect or identify the analyte in 100 % of the cases).
      It should be noted that the two approaches are only valid for a linear curve and therefore linearity has to be proven in order to use these approaches.”

所以，个人认为，如何制定特定分析方法最低残留限量(或者说最小执行限量)标准，这依赖于你所采用的分析方法，你要的答案应该在你自己的实验数据里！

不变的法则是——某个具体药物最大残留限量标准，应符合分析方法的最低检出限。这点，偶个人打包票是千真万确滴！！！

一句话：信噪比法计算检测限和定量限肯定是可行的，除非你说统计学不是科学，或者说你不是在科学地使用统计学。^_^

ps：上述言论，纯属个人一孔之见，仅供交流切磋，对与错，大伙自己定夺。

不是好像欧盟也要象日本那样实行没有具体值的按0.01执行了吗?

检测限（CCα）和定量限(CCβ)这两个值按照欧盟2002/657/EC计算的话，在什么情况下用什么方式计算还是一知半解的，不知道大家是做何感想的。

下面是欧盟2002/657/EC中的原话：
The decision limit has to be established according to the requirements for identification or identification plus
quantification as defined under ‘Performance criteria and other requirements for analytical methods’ (part 2).

In the case of substances for which no permitted limit has been established, CCα can be established:
— either by the calibration curve procedure according to ISO 11843 (17) (here referred to as critical value of the
net state variable). In this case blank material shall be used, which is fortified at and above the minimum
required performance level in equidistant steps. Analyse the samples. After identification, plot the signal
against the added concentration. The corresponding concentration at the y-intercept plus 2,33 times the
standard deviation of the within-laboratory reproducibility of the intercept equals the decision limit. This is
applicable to quantitative assays only (α = 1 %),
— or by analysing at least 20 blank materials per matrix to be able to calculate the signal to noise ratio at the
time window in which the analyte is expected. Three times the signal to noise ratio can be used as decision
limit. This is applicable to quantitative and qualitative assays.

In the case of substances an with established permitted limit, CCα can be established:
— either by the calibration curve procedure according to ISO 11843 (17) (here referred to as critical value of the
net state variable). In this case blank material shall be used, which is fortified around the permitted limit in
equidistant steps. Analyse the samples. After identification, plot the signal against the added concentration.
The corresponding concentration at the permitted limit plus 1,64 times the standard deviation of the
within-laboratory reproducibility equals the decision limit (α = 5 %),
— or by analysing at least 20 blank materials per matrix fortified with the analyte(s) at the permitted limit. The
concentration at the permitted limit plus 1,64 times the corresponding standard deviation equal the decision
limit( α = 5 %).
See also Article 5 and point 3.2.

3.1.2.6. Detection capability (CCβ)
The detection capability should be determined according to the requirements for screening, identification or
identification plus quantification as defined (see part 2).
In the case of substances for which no permitted limit has been established, CCβ can be established by:
— the calibration curve procedure according to ISO 11843 (17) (here referred to as minimum detectable value
of the net state variable). In this case representative blank material shall be used, which is fortified at and
below the minimum required performance level in equidistant steps. Analyse the samples. After identification,
plot the signal against the added concentration. The corresponding concentration at the decision limit plus
1,64 times the standard deviation of the within-laboratory reproducibility of the mean measured content at
the decision limit equals the detection capability (β = 5 %),
— analysing at least 20 blank materials per matrix fortified with the analyte(s) at the decision limit. Analyse the
samples and identify the analytes. The value of the decision limit plus 1,64 times the standard deviation of
the within-laboratory reproducibility of the measured content equals the detection capability (β = 5 %),
— where no quantitative results are available, the detection capability can be determined by the investigation of
fortified blank material at and above the decision limit. In this case the concentration level, where only ≤ 5 %
false compliant results remain, equals the detection capability of the method. Therefore, at least 20
investigations for at least one concentration level have to be carried out in order to ensure a reliable basis for
this determination.

In the case of substances for which a permitted limit has been established, CCβ can be established:
— either by the calibration curve procedure according to ISO 11843 (17) (here referred to as minimum
detectable value of the net state variable). In this case representative blank material shall be used, which is
fortified around the permitted limit in equidistant steps. Analyse the samples and identify the analyte(s).
Calculate the standard deviation of the mean measured content at the decision limit. The corresponding
concentration at the value of the decision limit plus 1,64 times the standard deviation of the within-laboratory
reproducibility equals the detection capability (β = 5 %),
— or by analysing at least 20 blank materials per matrix fortified with the analyte(s) at the decision limit. The
value of the decision limit plus 1,64 times the corresponding standard deviation equals the detection
capability (β = 5 %).
See also section 3.2.

3楼回答很详细啊！

原文由 luxw 发表:
3楼回答很详细啊！

要完全按照欧盟2002/657/EC去分析啊，不管什么贸不贸易壁垒的，现在要想发文章已经容不得什么三倍信噪比，十倍信噪比的算法了。

到底该怎么算呢，还是很茫然啊

各位同仁，具体是如何操作的呀，我们单位现在正在弄LOD，LOQ，急啊

CCα(μgkg−1)= a/b + 2.33Sa/b (α= 1%) and CCβ(μgkg−1)=CCα+ 1.64Sa/b (β= 5%), where a is the intercept of the
standard addition curve, b is the slope of the
standard addition curve and Sa is the standard error of the intercept.