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. 2018 Aug 15;4(8):FSO331.
doi: 10.4155/fsoa-2018-0039. eCollection 2018 Sep.

Quantitation of paracetamol by liquid chromatography-mass spectrometry in human plasma in support of clinical trial

Richard Kin-Ting Kam  1   1 , Michael Ho-Ming Chan  1   1 , Hiu-Ting Wong  1   1 , Aniruddha Ghose  2   2 , Arjen M Dondorp  3   3 , Katherine Plewes  3   3 , Joel Tarning  3   4   3   4
Affiliations

Quantitation of paracetamol by liquid chromatography-mass spectrometry in human plasma in support of clinical trial

Richard Kin-Ting Kam et al. Future Sci OA. .

Abstract

Aim: Paracetamol is a well-tolerated antipyretic widely used in severe malaria management. The study aimed to develop and validate a rapid LC-MS/MS assay to quantify paracetamol in plasma from patients with severe malaria.

Materials & methods: Plasma sample was precipitated by organic solvent containing isotope-labeled paracetamol internal standard. Supernatant was isolated, diluted with water, followed by LC-MS/MS analysis.

Results: Plasma samples were extracted and assayed in less than 5.5 min. The assay response was linear (0.125-50 mg/l) with total intra- and interassay imprecision of <1.4%, which were considerably lower than most published reports.

Conclusion: We developed, validated and applied a rapid and small volume LC-MS/MS assay with high precision and accuracy for plasma paracetamol quantitation in 989 samples from 62 patients with severe malaria. The simple and high-throughput quality could facilitate assay automation for future clinical studies.

Keywords: LC–MS/MS; acetaminophen; bioanalysis; malaria; paracetamol.

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Conflict of interest statement

Financial & competing interests disclosure This study was part of Mahidol-Oxford Tropical Medicine Research Unit (MORU), Bangkok, Thailand core malaria research supported by the Wellcome Trust of Great Britain [grant number A-15–0001]. RK-T Kam, H-T Wong and the LC–MS/MS instruments were financially supported by Phase I Clinical Trial Center, The Chinese University of Hong Kong. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Extracted ion chromatograms of paracetamol (left column) and paracetamol-D4 (right column).
(A) Plasma blank, (B–E) QC samples spiked with paracetamol at (B) 0.125 mg/l (LLOQ), (C) 0.25 mg/l, (D) 5 mg/l and (E) 30 mg/l. Extracted ion chromatograms of paracetamol-D4 represented post-extraction concentration of 3.8 mg/l. LLOQ: Lower limit of quantitation; QC: Quality control.
<b>Figure 1.</b>
Figure 1.. Extracted ion chromatograms of paracetamol (left column) and paracetamol-D4 (right column).
(A) Plasma blank, (B–E) QC samples spiked with paracetamol at (B) 0.125 mg/l (LLOQ), (C) 0.25 mg/l, (D) 5 mg/l and (E) 30 mg/l. Extracted ion chromatograms of paracetamol-D4 represented post-extraction concentration of 3.8 mg/l. LLOQ: Lower limit of quantitation; QC: Quality control.
<b>Figure 2.</b>
Figure 2.. Measured concentration–time profiles of paracetamol in patients with malaria, after a single oral dose of 1 g paracetamol (n = 5).
See this image and copyright information in PMC

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