Quantification of the Active Metabolites 4-Methylaminoantipyrine and 4-Aminoantipyrine of Dipyrone From Human Plasma by LC–MS/MS

Schmidt S, Ihmsen H, Golditz T, Schüttler J, Wehrfritz A (2026)

Publication Type: Journal article

Publication year: 2026

Journal

International Journal of Analytical Chemistry Hindawi Publishing Corporation

Book Volume: 2026

Article Number: 9944493

Journal Issue: 1

DOI: 10.1155/ianc/9944493

Abstract

Dipyrone (metamizole) is widely used as a nonopioid analgesic in perioperative and intensive care settings; however, its administration may be associated with severe adverse effects. In this study, we describe an analytical assay for the quantification of the active metabolites 4-methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA) in human plasma using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC–MS/MS). In addition, the protein-unbound fractions of both metabolites were determined by ultrafiltration. Chromatographic separation was performed on a UPLC system using gradient elution, followed by MS/MS detection with an electrospray ionization source. The limits of detection for both metabolites were 100 ng/mL. Across the investigated concentration range (100–10,000 ng/mL), the relative error (%RE) ranged from −6.3% to +3.5%. Intra-day and inter-assay variability were below 10%. Method validation was conducted in accordance with the 2018 FDA Bioanalytical Method Validation Guidance, and all evaluated parameters met the required criteria for analytical accuracy and precision. The developed assay is suitable for monitoring dipyrone metabolites and may support the prevention of potential overdosing during prolonged analgesic therapy or in intensive care settings.

Authors with CRIS profile

Stefanie Schmidt Department of Anaesthesiology Harald Ihmsen Department of Anaesthesiology Tobias Golditz Department of Anaesthesiology Jürgen Schüttler Department of Anaesthesiology Andreas Wehrfritz Department of Anaesthesiology

How to cite

APA:

Schmidt, S., Ihmsen, H., Golditz, T., Schüttler, J., & Wehrfritz, A. (2026). Quantification of the Active Metabolites 4-Methylaminoantipyrine and 4-Aminoantipyrine of Dipyrone From Human Plasma by LC–MS/MS. International Journal of Analytical Chemistry, 2026(1). https://doi.org/10.1155/ianc/9944493

MLA:

Schmidt, Stefanie, et al. "Quantification of the Active Metabolites 4-Methylaminoantipyrine and 4-Aminoantipyrine of Dipyrone From Human Plasma by LC–MS/MS." International Journal of Analytical Chemistry 2026.1 (2026).

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