Metabolomics Methods for Detecting Acetaminophen Poisoning: A Systematic Review

Introduction: Detecting toxicity patterns in metabolic changes is a key indicator of potential threats. Metabolomics may provide an alternative way to find biomarkers for drug overdose and toxicity. In an acetaminophen overdose, glutathione scavenging causes mitochondrial malfunction and hepatocyte death. Metabolomics methods have enabled the discovery of novel mechanisms of liver injury in acetaminophen (APAP) overdose. Methods: We conducted a peer-reviewed scientific review to assess the studies on the application of metabolomics in APAP poisoning. We searched PubMed and Scopus databases until February 28, 2025, for relevant original articles. We also looked into the clinicaltrials.gov website and the Indian clinical trial registry. Results: Our initial search yielded 302 articles, after duplicates and initial screening. Two hundred and nine (209) articles underwent full-text review. Of these, 191 articles were excluded, and 18 studies were included. There were 1503 subjects, and 24 metabolomics techniques were used. Seven trials were registered in clinicaltrials.gov, and none were registered in the CTRI. Discussion: Metabolic intermediates are more likely to pass through intact cell membranes and be detected in blood before cell death. Thus, metabolomics could be a potential strategy to identify damage biomarkers relevant at earlier periods. Conclusion: APAP can be considered a multifunctional drug with significantly fewer adverse effects; however, it still affects the liver when used chronically. Scientists continue to push the boundaries of data extraction, and it is widely acknowledged that a lack of tools for data integration hampers the full manifestation of metabolomics technologies. This research increases our understanding of metabolomics use in APAP-induced liver injury.