Synthetic cannabinoids (SCs) are consumed as legal alternative to cannabis and often allow passing drug-screening tests. Their rapid transience on the drug scene, combined with their mostly unknown metabolic profiles, creates a scenario with constantly moving analytical targets, making their monitoring and identification challenging. The development of fast screening strategies for SCs, not directly focused on their chemical structure, as an alternative to the commonly applied target acquisition methods, would be highly appreciated in forensic and public health laboratories. An innovative untargeted metabolomics approach, focused on herbal components commonly used for ‘spice’ products, was applied. Saliva samples of healthy volunteers were collected at pre-dose and after smoking herbal components and analysed by high-resolution mass spectrometry. The data obtained, combined with appropriate statistical analysis, allowed to highlight and elucidate two markers (scopoletin and N,N-bis(2-hydroxyethyl)dodecylamine), which ratio permitted to differentiate herbal smokers from non-smokers. The proposed strategy will allow discriminating potential positives, on the basis of the analysis of two markers identified in the herbal blends. This work is presented as a step forward in SC drug testing, promoting a smart first-line screening approach, which will allow reducing the number of samples to be further investigated by more sophisticated HRMS methods.

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合成大麻素（SCs）是大麻的合法替代品，通常可以通过药物筛选测试。它们在药物现场的快速瞬变以及最不为人知的新陈代谢特征共同构成了一个分析目标不断变化的情况，从而使其监控和鉴定具有挑战性。法医和公共卫生实验室将高度赞赏SC的快速筛选策略的发展，而不是直接关注其化学结构，以替代常用的目标获取方法。应用了一种创新的，无目标的代谢组学方法，重点研究了常用于“香料”产品的草药成分。在服药前和吸烟后收集健康志愿者的唾液样本，并通过高分辨率质谱分析。N，N-双（2-羟乙基）十二烷基胺），该比率允许将草药吸烟者与非吸烟者区分开。所提出的策略将基于对草药混合物中鉴定出的两种标记物的分析，从而鉴别出潜在的阳性结果。这项工作是SC药物测试中迈出的一步，它促进了一种智能的一线筛查方法，这将减少通过更复杂的HRMS方法进一步研究的样品数量。

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