Investigating paracetamol pharmacokinetics using venous and capillary blood and saliva sampling

Abstract

Abstract Objective The aim of this study was to develop, validate and apply a high performance liquid chromatography (HPLC) assay for analysis of paracetamol, paracetamol glucuronide and paracetamol sulfate in plasma (venous and capillary) and saliva to study paracetamol pharmacokinetics in healthy volunteers. Methods Samples were prepared using protein precipitation and analysed using reverse phase HPLC with UV detection. This assay was applied to venous and capillary plasma and saliva samples from 20 healthy volunteers after paracetamol 1 g four times daily for three days. Key findings The HPLC assay for paracetamol and its metabolites was found to be sensitive and selective in plasma and saliva samples over the range 0.05–50 mg/l with an inter- and intraday precision and accuracy within 11.2% and 11.1%, respectively. Mean recoveries for all analytes were > 88%. A study of paracetamol pharmacokinetics in healthy volunteers found close agreement between the sampling matrices for paracetamol and metabolites (metabolites were not detected in saliva). The value for area under the concentration–time curve over the 6 h dosing interval of venous plasma (45.3 ± 12.9 mg/l.h) was significantly higher than that observed for capillary plasma (33.8 ± 12.9 mg/l.h) or saliva (35.1 ± 9.4 mg/l.h; P > 0.01). Conclusions Capillary blood and saliva collection were found to be reliable sampling matrices for the evaluation of paracetamol pharmacokinetics, although paracetamol metabolites were not detected in saliva.