Limit of blank, limit of detection and limit of quantitation

Abstract

* Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) are terms used to describe the smallest concentration of a measurand that can be reliably measured by an analytical procedure. * LoB is the highest apparent analyte concentration expected to be found when replicates of a blank sample containing no analyte are tested. LoB = mean(blank) + 1.645(SD(blank)). * LoD is the lowest analyte concentration likely to be reliably distinguished from the LoB and at which detection is feasible. LoD is determined by utilising both the measured LoB and test replicates of a sample known to contain a low concentration of analyte. * LoD = LoB + 1.645(SD (low concentration sample)). * LoQ is the lowest concentration at which the analyte can not only be reliably detected but at which some predefined goals for bias and imprecision are met. The LoQ may be equivalent to the LoD or it could be at a much higher concentration.

Figure

Relationship between LoB, LoD and LoQ. The solid line defines the LoB and represents the distribution of results for a blank specimen. As modern analysers seldom report results of less than zero, the frequency of “zero” results is artificially increased as illustrated. The LoB shown excludes a small proportion of blank results (“á”). The dashed line defines the LoD and represents the scatter (imprecision) of results for a specimen of low concentration. The LoD is then set so that only a small proportion (“â”) of these results will fall below LoB. The dotted line defines the LoQ and represents the distribution of results for a specimen of low concentration meeting the target for total error (imprecision and bias). It may be that this LoQ total target error is met by a specimen at the LoD concentration in which case LoQ = LoD. Otherwise, LoQ will have to be set after testing a specimen of higher concentration. Reproduced with permission, from NCCLS publication EP17-A, Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline.