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

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.

Lay abstract

Paracetamol is a commonly prescribed antipyretic in severe malaria management. Here, a rapid quantitative assay was developed to measure the plasma level of paracetamol. The developed method required levels as low as 20 μl plasma, and was highly precise, with a short analysis time of 5.5 min. The developed method is particularly suitable for clinical trial application and potentially for clinical use.