The formation of artefacts during the extraction and isolation of specialised metabolites is a significant issue in phytochemical research and related areas, including marine chemistry, and microbial metabolites studies. Artefacts arise when genuine natural products undergo chemical transformations induced by mechanical stress, heat, extraction, purification, storage conditions, enzymatic activity, and/or analytical procedures. Common transformation pathways include hydrolysis, oxidation, isomerisation, solvolysis, rearrangement, polymerisation, and alkylation (e.g., O-methylation). These processes are discussed using representative examples from major phytochemical classes, such as iridoids, sesquiterpene lactones, alkaloids, glucosinolates, and phenolic compounds. Considering these mechanisms of artefact formation, a best practice workflow is proposed in order to minimise artefact formation. The workflow includes systematic control strategies to reduce artefact generation and guidelines for defining appropriate control experiments prior to publishing natural products as genuine compounds. In this way, the reliability of the phytochemical literature can be enhanced. The proposed workflow covers recommendations for extraction planning, solvent selection, temperature and pH control, protection from light, oxygen and enzymes, stability testing, and transparent, systematic analytical validation. Awareness of the feasibility of artefact formation, together with transparent control experiments, will improve reproducibility, ensure structural accuracy, and facilitate more reliable interpretation of phytochemical data. Finally, guidance is provided on how to detect artefacts in previous publications and how to check for their occurrence in one's own work.
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