Tutorial on estimating the limit of detection using LC-MS analysis,part I: Theoretical review

A large body of literature exists on the limit of detection (LOD), but there is still a lot of confusion about this important validation parameter. This confusion mainly stems from its statistically complex background. The goal of this two-part tutorial is to discuss and clarify the topic of LOD for practitioners. The two main conclusions of this tutorial are: (1) the choice of how to estimate LOD should be based on the purpose of the analytical method that is being validated (e.g. considerable effort should not be made to estimate LOD for a method that is not used for detecting traces in the vicinity of LOD), and (2) LOD estimates are strongly dependent on different assumptions and the approach used, and therefore caution must be exercised when using the estimate or when comparing different estimates.