Can an analytical method's limit of quantification (LOQ) be outside its linear dynamic range, or is it always required to be within it? Please provide a thorough explanation supported by verified references.
The Limit of Quantification (LOQ) is typically expected to fall within the Linear Dynamic Range (LDR) of an analytical method. This ensures reliable quantification and adheres to most regulatory guidelines. While theoretically possible in some specialized cases, having the LOQ outside the LDR is generally not recommended for standard analytical practices.
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Is the measured range expected to be linear across the range ? Depending on the detector type and signal response, it may or may not be. Establishing the "analysis method" and measuring the ACTUAL signal response would establish this for each sample. This process allows us to measure the actual response for the proposed method rather than assume it may or may not be valid. LOQ should be within the measured range.
You have asked a bit of a trick question... and also not stated for what type of technique and/or detector is used? The LOQ may fall outside of a "Linear Range". However, this may indicate that measurement range used was incomplete (the method is invalid) OR:
(1) The analysis method's range was not fully measured to determine the correct curve fit possible. Measurements made must be within the range and include enough points to correctly describe the response.
(2) The method describes a technique where the actual output is measured to be non-linear (so no linear range would be expected in one or more portions of the curve). In cases where a non-linear range is expected (common with some detector types such as CAD, ELSD etc), the multi-level calibration ranges used for each sample would include MANY different concentration points ('levels'), per order of magnitude, to reliably describe the complete curve-fit in enough detail that it can be used to make measurements from. Measurements made must be still be within the range, even if it is non-linear.
Ideally, output should be linear across all measured ranges with a zero or "near zero" intercept. This type of output allows for the most predictable data set which is easier to verify. Is linearity required? NO. As long as you can apply the scientific method to the measurement used and demonstrate reproducible and accurate results using a properly developed method of analysis it should be fine. As with all measurements, the LOQ should be within the measured range.
Summary: In ALL cases, ALL of the limits described, as part of the overall method, shall be WITHIN the measured range (*This includes LOD and LOQ).
The Limit of Quantification (LOQ) is the lowest concentration at which a substance can be reliably quantified with acceptable accuracy and precision, as defined by international analytical validation guidelines (e.g., FDA, Eurachem, ISO). According to these guidelines, the LOQ represents the starting point of the linear dynamic range of an analytical method.
While some studies might report linear ranges extending below the LOQ, it is important to note that any quantification made below this limit may not meet the required standards of accuracy and precision. In other words, below the LOQ, the analytical method’s performance is not sufficiently reliable, and therefore, the data obtained may not be considered valid for accurate quantification.
The linearity of any quantification method will be determined from LOQ to 120% or 150% of the specification limit. Sometimes the LOQ concentration is determined by the S/N ratio method, it satisfies the S/N requirement, and that concentration may not be precise, accurate, or linear. in that case one can change the LOQ concentration, where it satisfies the requirement of precision, accuracy, and linearity, that concentration can be considered the LOQ concentration of the method.
It's important that the LOQ falls within the range of linearity of the analytical method. The linear range is the range of analyte concentrations over which the instrument response is directly proportional to the concentration of the analyte.
Ensuring that the LOQ is within the linear range ensures accurate and reliable measurements. If the LOQ is outside the linear range, the method may not provide accurate quantitative data because the instrument response might not accurately reflect changes in analyte concentration.
Read William Letter 's response. It is correct. Some detectors are very reproducible within a given method, yet have a non-linear response to analytes.