Utilization of Data Below the Analytical Limit of Quantitation in Pharmacokinetic Analysis and Modeling: Promoting Interdisciplinary Debate
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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Concentration data below LOQ but not below LOD were included to evaluate the excretion profile because inclusion can result in a better fit and excluding or replacing them with zero could lead to biased pharmacokinetic parameters.
“Concentration data below the LOQ (but not below the LOD) were included to evaluate the excretion profile, as their inclusion can result in a better fit of the excretion profile model, while excluding or replacing them with zero could lead to biased pharmacokinetic parameters [39,40,41,42].”
From Urinary Elimination of Ecdysterone and its Metabolites following a Single-Dose Administration in Humans (2021) · cites this paper as [41]
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References 252 · Cited by 34
- Authors
- Hecht, M., Veigure, R., Couchman, L., S Barker, C. I., Standing, J. F., Takkis, K., Evard, H., Johnston, A., Herodes, K., Leito, I., & Kipper, K.
- Affiliations
- St George's, University of London (GB)
- Chair of Analytical Chemistry, Institute of Chemistry, University of Tartu, 14a Ravila Street, 50411Tartu, Estonia
- Paediatric Infectious Diseases Research Group, Institute for Infection & Immunity, St George's University of London, London, SW17 0RE, UK
- University of Tartu (EE)
- ORCID
- Venue
- Bioanalysis
- Publisher
- Informa UK Limited
- Published
- 2018-07-23
- Volume
- 10
- Issue
- 15
- Pages
- 1229-1248
- ISSN
- 1757-6180 (ISSN-L)
- 1757-6199
- OpenAlex
- W2883148506
- Cited by
- 34
- References
- 252
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 7 · 2023: 1 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 3
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bioanalysis (publishedVersion)
- PubMed (publishedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- UK NIH Research (ACF-2016-18-016)
- UK Medical Research Council Fellowships (G1002305, M008665)
- Ministry of Education and Research of Estonia (TLOKT14014I)
- Topics
- Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Keywords
- detection limit, pharmacokinetic analysis, pharmacokinetic modeling, method validation, imprecise data, regulatory guidelines, pharmacometrics
- MeSH terms
- Chromatography, Gas, Chromatography, Liquid, Pharmaceutical Preparations, Models, Theoretical, Pharmacokinetics, Reproducibility of Results, Guidelines as Topic, Government Regulation, Limit of Detection
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