Rapid and Non-invasive Analysis of Paracetamol Overdose Using Paper Arrow-mass Spectrometry: a Prospective Observational Study

Overview

Journal BMC Med

Publisher Biomed Central

Specialty General Medicine

Date 2024 Nov 26

PMID 39587595

Authors

Yufeng Zhou

Silothabo Dliso

Jennie Craske

Andrea Gill

Louise Bracken

Kiran Landa

Philip Arnold

Laura Walker

Ionela Grasim

Gabrielle Seddon

Tao Chen

Andrew S Davison

Tung-Ting Sham

Barry Smith

Daniel B Hawcutt

Simon Maher

Affiliations

Soon will be listed here.

Abstract

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.

References

Bland J, Altman D . Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986; 1(8476):307-10. View

Akoglu H . User's guide to correlation coefficients. Turk J Emerg Med. 2018; 18(3):91-93. PMC: 6107969. DOI: 10.1016/j.tjem.2018.08.001. View

Idkaidek N, Arafat T . Saliva versus plasma pharmacokinetics: theory and application of a salivary excretion classification system. Mol Pharm. 2012; 9(8):2358-63. DOI: 10.1021/mp300250r. View

Idkaidek N, Arafat T . Saliva vs. plasma bioequivalence of paracetamol in humans: validation of class I drugs of the salivary excretion classification system. Drug Res (Stuttg). 2014; 64(10):559-62. DOI: 10.1055/s-0033-1363995. View

Gorodischer R, Burtin P, Hwang P, Levine M, Koren G . Saliva versus blood sampling for therapeutic drug monitoring in children: patient and parental preferences and an economic analysis. Ther Drug Monit. 1994; 16(5):437-43. DOI: 10.1097/00007691-199410000-00001. View

Jeong H, Cha K, Choi K, So B . Evaluation of cut-off values in acute paracetamol overdose following the United Kingdom guidelines. BMC Pharmacol Toxicol. 2022; 23(1):5. PMC: 8734297. DOI: 10.1186/s40360-021-00547-1. View

Zhou Y, Sham T, Boisdon C, Smith B, Blair J, Hawcutt D . Emergency diagnosis made easy: matrix removal and analyte enrichment from raw saliva using paper-arrow mass spectrometry. Analyst. 2023; 148(21):5366-5379. DOI: 10.1039/d3an00850a. View

Lindgren B, Lundman B, Graneheim U . Abstraction and interpretation during the qualitative content analysis process. Int J Nurs Stud. 2020; 108:103632. DOI: 10.1016/j.ijnurstu.2020.103632. View

Lin L . A concordance correlation coefficient to evaluate reproducibility. Biometrics. 1989; 45(1):255-68. View

10.

McGill M, Jaeschke H . Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharm Res. 2013; 30(9):2174-87. PMC: 3709007. DOI: 10.1007/s11095-013-1007-6. View

11.

Chidiac A, Buckley N, Noghrehchi F, Cairns R . Paracetamol (acetaminophen) overdose and hepatotoxicity: mechanism, treatment, prevention measures, and estimates of burden of disease. Expert Opin Drug Metab Toxicol. 2023; 19(5):297-317. DOI: 10.1080/17425255.2023.2223959. View

12.

Capiau S, Veenhof H, Koster R, Bergqvist Y, Boettcher M, Halmingh O . Official International Association for Therapeutic Drug Monitoring and Clinical Toxicology Guideline: Development and Validation of Dried Blood Spot-Based Methods for Therapeutic Drug Monitoring. Ther Drug Monit. 2019; 41(4):409-430. DOI: 10.1097/FTD.0000000000000643. View

13.

GLYNN J, Bastain W . Salivary excretion of paracetamol in man. J Pharm Pharmacol. 1973; 25(5):420-1. DOI: 10.1111/j.2042-7158.1973.tb10042.x. View

14.

Smith B, Hankinson T, Maher S . Portable Instrumentation for Ambient Ionization and Miniature Mass Spectrometers. Annu Rev Anal Chem (Palo Alto Calif). 2024; 17(1):69-102. DOI: 10.1146/annurev-anchem-061522-040824. View

15.

Davidson D, Eastham W . Acute liver necrosis following overdose of paracetamol. Br Med J. 1966; 2(5512):497-9. PMC: 1943529. DOI: 10.1136/bmj.2.5512.497. View

16.

Li Wan Po A, McKiernan P, Glasgow J, Millership J . Assay of paracetamol and its metabolites in urine, plasma and saliva of children with chronic liver disease. J Pharm Biomed Anal. 1995; 13(8):1033-9. DOI: 10.1016/0731-7085(95)01303-3. View

17.

Rumgay H, Arnold M, Ferlay J, Lesi O, Cabasag C, Vignat J . Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol. 2022; 77(6):1598-1606. PMC: 9670241. DOI: 10.1016/j.jhep.2022.08.021. View

18.

Liao J, Lewis J . A note on concordance correlation coefficient. PDA J Pharm Sci Technol. 2000; 54(1):23-6. View

19.

Soderstrom J, Fatovich D, Mandelt C, Vasikaran S, McCoubrie D, Daly F . Correlation of paired toxic plasma and saliva paracetamol concentrations following deliberate self-poisoning with paracetamol. Br J Clin Pharmacol. 2011; 74(1):154-60. PMC: 3394140. DOI: 10.1111/j.1365-2125.2011.04157.x. View

20.

Bateman D, Dart R, Dear J, Prescott L, Rumack B . Fifty years of paracetamol (acetaminophen) poisoning: the development of risk assessment and treatment 1973-2023 with particular focus on contributions published from Edinburgh and Denver. Clin Toxicol (Phila). 2024; 61(12):1020-1031. DOI: 10.1080/15563650.2023.2293452. View