Limit of detection defined

LOD—limit of detection—defined as the analyte concentration interpolated from a standard curve at a response level equivalent to zero concentration plus three standard deviations... 

Another data quality criterion required to properly evaluate measurement results is the limit of detection of that measurement. For measurements to be useful, the range of the measurement which is of interest for biological monitoring purposes must lie entirely above the limit of detection defined for that measurement. 

The method limit of quantitation and limit of detection must be determined as well as the limit of linearity. The limit of quantitation is defined as the level at which the measurement is quantitatively meaningful the limit of detection is the level at which the measurement is larger than the uncertainty and the limit of linearity is the upper level of the measurement rehabihty (39). These limits are determined by plotting concentration vs response. 

Immunoassays. Immunoassays (qv) maybe simply defined as analytical techniques that use antibodies or antibody-related reagents for selective deterrnination of sample components (94). These make up some of the most powerflil and widespread techniques used in clinical chemistry. The main advantages of immunoassays are high selectivity, low limits of detection, and adaptibiUty for use in detecting most compounds of clinical interest. Because of their high selectivity, immunoassays can often be used even for complex samples such as urine or blood, with Httle or no sample preparation. 

What is meant by the selectivity of a detector Define the limit of detection of a detector. 

The limit of detection is the smallest amount of an analyte that is required for reliable determination, identification or quantitation. More mathematically, it may be defined as that amount of analyte which produces a signal greater than the standard deviation of the background noise by a defined factor. Strictly for quantitative purposes, this should be referred to as the limit of determination . The factor used depends upon the task being carried out and for quantitative purposes a higher value is used than for identification. Typical values are 3 for identification and 5 or 10 for quantitation. 

The limit of detection (LOD) (see Figure 2.6) is defined as the smallest quantity of an analyte that can be reliably detected. This is a subjective definition and to introduce some objectivity it is considered to be that amount of analyte which produces a signal that exceeds the noise by a certain factor. The factor used, usually between 2 and 10 [11], depends upon the analysis being carried out. Higher values are used for quantitative measurements in which the analyst is concerned with the ability to determine the analyte accurately and precisely. 

The limit of determination [or limit of quantitation (LOQ)] is defined in Directive 96/46/EC as the lowest concentration tested at which an acceptable mean recovery (normally 70-110%) and acceptable relative standard deviation (normally <20%) are obtained. The specific requirements for LOQ in crops, food, feed, soil, drinking and surface water, air, body fluids, and tissues are described in Section 4. Because the abbreviation LOD usually means limit of detection rather than limit of determination, the authors prefer not to use this abbreviation here in order to avoid confusion, and LOQ is used throughout. According to Directive 96/46/EC no data with regard to the limit of detection must be given. 

Today, when a pesticide with no detectable residues is registered for use, a Tolerance or maximum residue limit (MRL) is established at the lowest concentration level at which the method was validated. However, for risk assessment purposes it would be wrong to use this number in calculating the risk posed to humans by exposure to the pesticide from the consumption of the food product. This would be assuming that the amount of the pesticide present in all food products treated with the pesticide and for which no detectable residues were found is just less than the lowest level of method validation (LLMV). The assumption is wrong, but there is no better way of performing a risk assessment calculation unless the limit of detection (LOD) and limit of quantification (LOQ) of the method were clearly defined in a uniformly acceptable manner. 

Several terms have been used to define LOD and LOQ. Before we proceed to develop a uniform definition, it would be useful to define each of these terms. The most commonly used terms are limit of detection (LOD) and limit of quantification (LOQ). The 1975 International Union of Pure and Applied Chemistry (lUPAC) definition for LQD can be stated as, A number expressed in units of concentration (or amount) that describes the lowest concentration level (or amount) of the element that an analyst can determine to be statistically different from an analytical blank 1 This term, although appearing to be straightforward, is overly simplified. If leaves several questions unanswered, such as, what does the term statistically different mean, and what factors has the analyst considered in defining the blank Leaving these to the analyst s discretion may result in values varying between analysts to such an extent that the numbers would be meaningless for comparison purposes. 

Sensitivity is a measure of the smallest concentration that can be either measured [limit of detection (LOD)] or accurately quantitated [limit of quantitation (LOQ)]. In the USA, the method for measuring LOD or LOQ is left up to the method developer. European requirements for determining LOD and LOQ are very specific the LOD is based on the mean plus three standard deviations for 20 control blank samples, and the LOQ is defined as the lowest concentration giving an acceptable CV. 

Limits of detection for each of the three parent herbicides in surface and groundwater were determined using results obtained from control samples analyzed along with hundreds of surface and ground water sets during the years 1995-2001. In each of these years, the calculated LODs (minimum detectable true concentrations/detection) were below 0.03 pg for acetochlor and metolachlor and 0.05 pg for alachlor. A detection criterion is a measured concentration threshold that defines a likely upper bound for samples not containing the analyte. If the actual concentration of an analyte is at this detection limit or greater, there is at least a 95% chance of detection. 

Assay sensitivity is defined here as the concentration of analyte that inhibits the observed absorbance by 50% or the IC50. The lower limit of detection (LLD) is the lowest analyte concentration that elicits a detector response significantly different from the detector response in the absence of analyte. In some cases, the LLD is defined as three standard deviations from the mean of the zero analyte control. In other cases, the LLD is defined empirically by determining the lowest concentration of analyte that can be measured with a given degree of accuracy. Readers are referred to Grotjan and Keel for a simplified explanation and to Rodbard for the complete mathematics on the determination of LLD. 

Net recoveries of cyfluthrin from matrices fortified at 0.01-5.05 mg kg ranged from 77 to 119%. The limit of detection (LOD) is defined as the lowest concentration that can be determined to be statistically different from a blank or control. Calculate the value by taking the standard deviation of the residue values from the analysis of the recovery samples at the limit of quantification (LOQ) and using the equation... 

Method validation is defined in the international standard, ISO/IEC 17025 as, the confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use are fulfilled. This means that a validated method, if used correctly, will produce results that will be suitable for the person making decisions based on them. This requires a detailed understanding of why the results are required and the quality of the result needed, i.e. its uncertainty. This is what determines the values that have to be achieved for the performance parameters. Method validation is a planned set of experiments to determine these values. The method performance parameters that are typically studied during method validation are selectivity, precision, bias, linearity working range, limit of detection, limit of quantitation, calibration and ruggedness. The validation process is illustrated in Figure 4.2. 

The limit of detection (LoD) has already been mentioned in Section 4.3.1. This is the minimum concentration of analyte that can be detected with statistical confidence, based on the concept of an adequately low risk of failure to detect a determinand. Only one value is indicated in Figure 4.9 but there are many ways of estimating the value of the LoD and the choice depends on how well the level needs to be defined. It is determined by repeat analysis of a blank test portion or a test portion containing a very small amount of analyte. A measured signal of three times the standard deviation of the blank signal (3sbi) is unlikely to happen by chance and is commonly taken as an approximate estimation of the LoD. This approach is usually adequate if all of the analytical results are well above this value. The value of Sbi used should be the standard deviation of the results obtained from a large number of batches of blank or low-level spike solutions. In addition, the approximation only applies to results that are normally distributed and are quoted with a level of confidence of 95%. 

Quantification of the limits of detection (LOD), or minimum detectable levels (MDL statistically defined in Section 13.4), is an important part of any analysis. They are used to describe the smallest concentration of each element which can be determined, and will vary from element to element, from matrix to matrix, and from day to day. Any element in a sample which has a value below, or similar to, the limits of detection should be excluded from subsequent interpretation. A generally accepted definition of detection limit is the concentration equal to a signal of twice (95% confidence level) or three times (99% confidence) the standard deviation of the signal produced by the background noise at the position of the peak. In practice, detection limits in ICP-MS are usually based on ten runs of a matrix matched blank and a standard. In this case ... 

The minimum detectable level, or detection limit, is defined as that concentration of a particular element which produces an analytical signal equal to twice the square root of the background above the background. It is a statistically defined term, and is a measure of the lower limit of detection for any element in the analytical process. (This definition corresponds to the 95% confidence interval, which is adequate for most purposes, but higher levels, such as 99% can be defined by using a multiplier of three rather than two.) It will vary from element to element, from machine to machine, and from day to day. It should be calculated explicitly for every element each time an analysis is performed. 

Part B information to be defined by the FSA customer once the contract has been awarded to a contractor, e.g. the sample storage conditions to be used, the methods to be used, the IQC procedures to be used, the required measurement limits (e.g. limit of detection (LOD), limit of determination/ quantification (LOQ), and the reporting limits)... 

---