Validation of Chromatographic Methods: Determining the Limit of Quantification in Practice

Key issues related to determining the limit of quantification (LOQ) in practice are considered. Requirements to the value of LOQ and its precision and accuracy are formulated. It is shown that the use of a calibration curve for LOQ determination may result in erroneous conclusions for impurity determination methods. Answers to a number of questions relevant to practice are given. The precision of the LOQ value should always be checked if the LOQ is determined from a calibration curve. A typical requirement for LOQ precision is RSD ≤ 5.0%. An RSD ≤ 10% is acceptable in exceptional cases of a very low LOQ concentration. For this, the validation documentation should visually confirm the acceptability of the LOQ value by a chromatogram of a solution of the determined substance with the LOQ concentration.