Hello.

By Limit of Quantitation (LOQ) we refer to the lowest concentration of an analyte we can quantify. I know by the name itself you can't really derive that because "the limit" should have a low and high point, but it's the way it has been defined for decades. The reason the LOQ also has that statement for "quantified with precision and accuracy" is because you are expected to do the LOQ in replicate analysis and report the %RSD for the replicates and the %recovery against the theoretical spike concentration (if you are doing spiked study into placebo or matrix of sort).

The high end of that limit is established by running Linearity and Range and/or Accuracy and Range studies. Per ICH Q2, "The range of an analytical procedure is the interval between the lowest and the highest results in which the analytical procedure has a suitable level of response, accuracy and precision." During accuracy and range study you would normally prepare replicates at each low (LOQ), middle (target or normally expected value), and high range and report %RSD and %recovery against the theoretical spike (if there was one); in terms of singal-to-noise ratio, if your method meets the requirement for NLT 10 at the LOQ level, there is obviously no need to report it for the higher levels because for the middle and high levels that would be in the thousands or tenths of thousand.

Commonly used references for these definitons are:

1) ICH HARMONISED GUIDELINE

VALIDATION OF ANALYTICAL PROCEDURES Q2(R2)

https://database.ich.org/sites/default/files/ICH_Q2%28R2%29_Guideline_2023_1130.pdf

2) USP Chapter 〈1225〉 VALIDATION OF COMPENDIAL PROCEDURES

(you need paid subscription for the most up to date version but you can find older version that are just fine by a Google search)

The Limit of Quantification (LOQ) is defined as the lowest concentration that can be accurately and precisely quantified, focusing on low-level detection. Including a "highest" concentration in this definition is unnecessary, as LOQ specifically addresses the lower measurement limit rather than the overall dynamic range of the method.

2d ago

Negin Rahimi,

Kindly refer ICH Q2(R2) guidelines for understanding of definition of LOD ( Limit of Detection and LOQ (Limit of Quantification).

Refer response of Petroslav Chipinski for better explanation.