I know the difference between instrumental LOD and method LOD but my query is - in case of any sample whose concentration is zero or not detected by the instrumental LOD, is it possible to get method LOD for the same and how?
To determine the method detection limit (MDL) when the sample concentration is zero or below the instrumental limit, prepare spiked samples using reagent water with known concentrations of the analyte. Analyze multiple aliquots of these spiked samples and calculate the MDL based on the average concentration minus the blank measurement. This approach ensures that the method's sensitivity is accurately assessed, even in undetectable samples.
Kindly refer ICH Q2(R2)Guidelines for LOD & LOQ determination. Number of approaches given for LOD/LOQ determination. Out of it Linearity and Signal to Noise ratio method can be taken.
To determine the method detection limit (MDL) in an analytical method:
Prepare Standards: Analyze a series of low-concentration standards, typically near the expected MDL.
Calculate Mean and Standard Deviation: Determine the mean and standard deviation of the blank or lowest standard.
Compute MDL: Use the formula MDL=mean of blanks+(t×standard deviation)\text{MDL} = \text{mean of blanks} + (t \times \text{standard deviation})MDL=mean of blanks+(t×standard deviation), where ttt is the t-value for a specified confidence level.
The MDL represents the lowest concentration that can be reliably distinguished from background noise.