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

Abstract

© 2018 Kin Ting Richard Kam. 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.