PI-046 - COMPARISON OF A COLORIMETRIC ASSAY AND ULTRA-PERFORMANCE LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETRY FOR QUANTIFYING PARACETAMOL PLASMA CONCENTRATIONS: DESIGN OF A GERIATRIC PHARMACOKINETICS STUDY.

A. Edwina¹, E. Dreesen^1,2, J. Hias^1,3, B. Koch⁴, N. Van Den Eede³, S. Pauwels⁵, K. Allegaert^1,6, L. Van der linden^1,3, I. Spriet^1,3, J. Tournoy^1,7; ¹Katholieke Universiteit Leuven, Leuven, Belgium, ²University of California, San Francisco, San Francisco, CA, USA, ³University Hospitals Leuven, Leuven, Belgium, ⁴Erasmus University Medical Center, Rotterdam, The Netherlands, ⁵Jessa Hospital, Hasselt, Belgium, ⁶Katholieke Universiteit Leuven, Leuven, Belgium, ⁷University Hospitals Leuven, Leuven, Belgium.

Background: Geriatric patients may be subjected to altered paracetamol pharmacokinetics (PK). So, more PK research is needed to optimize paracetamol dosing in these patients. Ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) is not always available in clinical routine. This study aims to evaluate the agreement between UPLC-MS/MS (reference method) and the more widely available colorimetric assay on a Cobas c702 platform (ACETA) for quantifying paracetamol plasma concentrations in future PK studies in geriatric patients.

Methods: Patient data and plasma samples were obtained from a prospective study including geriatric patients admitted to the geriatric wards in UZ Leuven, Belgium (1). 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 McNemar test. Population PK modeling was employed to bridge PK data obtained from both analysis methods (NONMEM 7.5).

Results: A total of 164 plasma samples from 39 patients (age range: 80-90 years) were available. 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) were not significantly different (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 1.01 (4%), yet with a 24.1% (18%) interindividual variability which could not be explained by any patient factors in a covariate analysis.

Conclusion: ACETA showed a good agreement with UPLC-MS/MS, making it a suitable alternative to UPLC-MS/MS for measuring paracetamol plasma concentrations in future PK studies.

1. Hias J, et al. Pharmacokinetics of 2 oral paracetamol formulations in hospitalized octogenarians. British Journal of Clinical Pharmacology.88(3):1020-1030 (2021)