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Utilization of data below the analytical limit of quantitation in pharmacokinetic analysis and modeling: promoting
Max Hecht1,2, Rūta Veigure1, Lewis Couchman2
1Chair of Analytical Chemistry, Institute of Chemistry, University of Tartu, 14a Ravila Street, 50411 Tartu, Estonia.
Abstract:
Traditionally, bioanalytical laboratories do not report actual concentrations for samples with results below the LOQ (BLQ) in pharmacokinetic studies. BLQ values are outside the method calibration range established during validation and no data are available to support the reliability of these values. However, ignoring BLQ data can contribute to bias and imprecision in model-based pharmacokinetic analyses. From this perspective, routine use of BLQ data would be advantageous. We would like to initiate an interdisciplinary debate on this important topic by summarizing the current concepts and use of BLQ data by regulators, pharmacometricians and bioanalysts. Through introducing the limit of detection and evaluating its variability, BLQ data could be released and utilized appropriately for pharmacokinetic research.
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