N-ethylhexedrone (NEH) and buphedrone (BUPH) are synthetic drugs structurally related to natural cathinone. These synthetic cathinones (SC) are members of the heterogenous family of new psychoactive substances (NPS), which have caused major concern in scientific and forensic communities over the past years, due to their widespread consume. Thus, there is a constant need for monitoring the use of these new substances and gather knowledge on their metabolism and excretion profiles, in order to try to identify markers of NPS consumption.

This study aimed at the identification and quantification of NEH, BUPH and selected phase I metabolites using HPLC-MS/MS. NEH, BUPH and some related metabolites were synthesized in-house and quantified in 24 h mice urine, following single dose administration of each drug (64 mg kg⁻¹, i.p.). NEH and BUPH were quantified in mice urine at 58.3 ± 14.4 and 146.2 ± 14.9 µg mL⁻¹, respectively. Similar metabolic pathways were observed for both drugs. Among the metabolites studied, the most excreted ones derived from N-dealkylation of either NEH or BUPH (at around 80 µg mL⁻¹ of urine). Other metabolites resulting from ketone reduction and ketone reduction combined with N-dealkylation or 4-aryl hydroxylation (detected for the first time in non-ring substituted SC) were also identified and quantified. Urine samples were screened using liquid chromatography-high resolution mass spectrometry and various phase II metabolites, including N-acetylated, glucuronides and dicarboxylic acid conjugates were tentatively identified, some of them for the first time. This work is a contribution to the identification of metabolites from SC that can become potential markers to estimate drug consumption.

N-乙基己酮（NEH）和丁苯丙酮（BUPH）是在结构上与天然卡西酮有关的合成药物。这些合成的卡西酮（SC）是新型精神活性物质（NPS）异质家族的成员，由于它们的广泛消费，近年来在科学和法医界引起了广泛关注。因此，始终需要监视这些新物质的使用并收集有关其新陈代谢和排泄概况的知识，以便尝试确定NPS消费的标志。

这项研究旨在使用HPLC-MS / MS鉴定和定量NEH，BUPH和所选的I期代谢物。在每种药物单次给药（64 mg kg ^-1，ip）后，内部合成NEH，BUPH和一些相关的代谢物并在24 h小鼠尿液中定量。小鼠尿液中NEH和BUPH的定量分别为58.3±14.4和146.2±14.9 µg mL ^-1。两种药物均观察到相似的代谢途径。在研究的代谢产物中，最分泌的代谢产物来自NEH或BUPH的N-脱烷基化（尿液浓度约为80 µg mL ^-1）。酮还原和酮还原与N结合产生的其他代谢物还鉴定和定量了-脱烷基或4-芳基羟基化（在非环取代的SC中首次检测到）。使用液相色谱-高分辨率质谱法筛选尿液样品，并初步鉴定出各种II期代谢物，包括N-乙酰化，葡糖醛酸苷和二羧酸共轭物，其中一些是首次。这项工作有助于鉴定来自SC的代谢物，这些代谢物可能成为估计药物消耗的潜在标记。