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Agreement Between a Colorimetric Assay and Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry for Quantifying Paracetamol Plasma Concentrations

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Abstract

Special populations, like geriatric patients, experience altered paracetamol pharmacokinetics (PK), complicating pain management. More PK research is essential to optimize paracetamol (acetaminophen) dosing. Yet, the reference method ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is not readily available. Therefore, we aimed to evaluate the agreement between UPLC-MS/MS and the more accessible colorimetric Roche acetaminophen (ACETA) assay in quantifying paracetamol plasma concentrations, to facilitate PK studies and therapeutic drug monitoring for pain management. Patient data and plasma samples were obtained from a prospective study including geriatric patients admitted to the geriatric wards. ACETA and UPLC-MS/MS assays were performed in two separate laboratories. Bland–Altman plot and Passing-Bablok regression were used to assess agreement. Accuracy was evaluated using the McNemar test for a threshold value of 10 mg/L. Population PK modeling was employed to bridge PK data obtained from both methods (NONMEM 7.5). A total of 242 plasma sample pairs were available from 40 geriatric patients (age range, 80–95 years). Paracetamol plasma concentrations from ACETA (median 9.8 [interquartile range 6.1–14.4] mg/L) and UPLC-MS/MS (9.5 [6.2–14.8] mg/L) did not differ significantly (P > 0.05). No significant proportional nor additive bias was observed between both assay methods. The classification accuracy (at threshold 10 mg/L) was 85% (P = 0.414). The conversion factor between ACETA and UPLC-MS/MS was estimated at 1.06 (relative standard error 5%), yet with a 13.4% (relative standard error 23%) interindividual variability. ACETA assay showed no systematic bias in comparison with the UPLC-MS/MS assay in determining paracetamol exposure in geriatric blood samples despite the imprecision.

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Acknowledgements

The resources and services used in this work were provided by the VSC (Flemish Supercomputer Center), funded by the Research Foundation—Flanders (FWO), and the Flemish Government.

Funding

This article receives no specific funding. AEE is supported by AGePOP, a Horizon 2020 research and innovation program; Marie Skłodowska-Curie grant (No. 956146).

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Authors and Affiliations

  1. Gerontology and Geriatrics, Department of Public Health and Primary Care, KU Leuven – University of Leuven, UZ Herestraat 49, Box 7003, 3000, Leuven, Belgium

    Angela Elma Edwina & Jos Tournoy

  2. Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven – University of Leuven, Leuven, Belgium

    Erwin Dreesen, Julie Hias, Karel Allegaert, Lorenz Van der Linden & Isabel Spriet

  3. Pharmacy Department, University Hospitals Leuven, Leuven, Belgium

    Julie Hias, Lorenz Van der Linden & Isabel Spriet

  4. Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, Netherlands

    Birgit C. P. Koch & Karel Allegaert

  5. Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium

    Nele Van den Eede

  6. Laboratory Medicine, Jessa Hospital, Hasselt, Belgium

    Steven Pauwels

  7. Department of Development and Regeneration, KU Leuven – University of Leuven, Leuven, Belgium

    Karel Allegaert

  8. Department of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium

    Jos Tournoy

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  1. Angela Elma Edwina
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Contributions

AEE, ED, JH, LVdL, IS, and JT made substantial contributions to the concept, design, and interpretation of data; JH, LVdL, IS, and JT collected the data; NVdE, SP, and BK performed the bioanalysis; AEE performed the data analysis and modeling and wrote the original draft; ED supervised the data analysis and modeling; KA, NVdE, SP, BK, ED, JH, LVdL, IS, and JT were involved in revising the manuscript critically for important intellectual content.

Corresponding author

Correspondence to Jos Tournoy.

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All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the Declaration of Helsinki and its later amendments. Informed consent was obtained from all individual participants involved in the study.

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Isabel Spriet and Jos Tournoy contributed equally to this work as senior authors.

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Edwina, A.E., Dreesen, E., Hias, J. et al. Agreement Between a Colorimetric Assay and Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry for Quantifying Paracetamol Plasma Concentrations. AAPS J 26, 23 (2024). https://doi.org/10.1208/s12248-024-00890-1

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