The “Limit of Detection (LOD)” or detection limit (DL) is the lowest concentration level of an analyte that can be determined during an analytical run.
Typically, the LOD is determined to be in the region where the “signal to noise ratio” is greater than 5. Limits of detection are specific to and are influenced by the matrix or buffer conditions, method, and analyte used.
In other words, the LOD is the minimum concentration of a substance or analyte which can be observed in a sample with a high degree of confidence if the analyte is present.
The LOD is the lowest concentration of a sample analyte that can be detected but not necessarily quantified.
The determination of detection limit requires
(1) some degree of confidence (usually 99% confidence level) that the analyte is
above a blank or background level, and
(2) that sample interferences are considered in this determination.
Usually, in analytical chemistry, the detection limit, the lower limit of detection, or LOD, refers to the lowest quantity of a substance that can be observed and which differs from the blank value, when now substance is present, within a stated confidence limit. This limit is generally around 1%. The detection limit can be estimated from the mean of the blank, the standard deviation of the blank and some confidence factor. The accuracy of the model used to predict the concentration from the raw analytical signal affects the detection limit as well.
Different definitions of "detection limits" are often used. These include
(i) the instrument detection limit (IDL),
(ii) the method detection limit (MDL),
(iii) the practical quantification limit (PQL), and
(iv) the limit of quantification (LOQ).
However, even when the same terminology is used, differences in the LOD may occur. The differences arise from what definition was used and what type of noise contributed to the measurement and calibration.
LOD and LOQ are analytical parameters that require validation in methods used for FDA GMP testing. Also, ICH defines the “detection limit of an individual analytical procedure as the lowest amount of analyte in a sample that can be detected but not necessarily quantified as an exact value. Therefore ths limit of detection (LOD) is the point at which a measured value is larger than the uncertainty associated with it.
FDA Guidelines for the validation of analytical methods 2015.
Ludwig Huber. Validation of Analytical methods. A Primer. 2010 Agilent Technologies.
ICH Guidelines: http://www.ich.org/products/guidelines.html.