Background: Paracetamol is the most consumed medicine globally. Its accessibility contributes to common overdose. Paracetamol overdose is responsible for > 50% of acute liver failure cases, making it the second most common reason for a liver transplant. Rapid quantitation of paracetamol is crucial to guide treatment of paracetamol overdose. Current tests require invasive sampling and relatively long turnaround times. Paper arrow-mass spectrometry (PA-MS) combines sample collection, extraction, separation, enrichment and ionisation onto a single paper strip, achieving rapid, accurate, cost-effective and eco-friendly analysis direct from raw human saliva.
Methods: To validate PA-MS against an established test, 17 healthy adults were recruited. Samples were collected before and at 15, 30, 60, 120 and 240 min after ingesting 1 g of paracetamol. Plasma measured with an established clinical test served as the reference standard to validate PA-MS with three biofluids-plasma, resting saliva (RS) and stimulated saliva (SS). Participants' views of blood, RS and SS sampling procedures were assessed qualitatively. Cross-validation was assessed using Lin's concordance correlation coefficients (CCC), Bland-Altman difference plots, and ratios of PA-MS to the reference standard test.
Results: PA-MS using stimulated saliva offers a reliable alternative to intravenous blood sampling. The CCC is 0.93, the mean difference with the reference test is - 0.14 mg/L, and the ratios compared to the reference test are 0.84-1.27 from correlated samples collected at 5 intervals over 4 h for each participant.
Conclusions: Paracetamol detection from SS with PA-MS provides a reliable result that can aid timely treatment decisions. Differences between paracetamol concentration in resting and stimulated saliva were also identified for the first time, highlighting the importance of standardising saliva collection methods in general. This study marks a major milestone towards rapid and convenient saliva analysis.
Keywords: Ambient ionisation; Mass spectrometry; Paper arrow-mass spectrometry; Paracetamol; Saliva.
© 2024. The Author(s).