In recent years, the rise in the synthesis and distribution of LSD analogs in illicit drug markets, commonly referred to as “designer psychedelics”, has contributed to increased recreational use. This trend has resulted in a rising number of global reports, with law enforcement increasingly detecting these compounds in blotter papers and biological samples. In the presented paper, an UHPLC-QqQ-MS/MS method was developed for trace determination (fg mL⁻¹) of LSD, its designer analogs (ALD-52, AL-LAD, LAMPA, LSM-775, LSZ, MiPLA, 1B-LSD, 1cP-LSD, 1cP-MiPLA, 1P-LSD, 1P-MiPLA, 1V-LSD and 2-Bromo-LSD) and its metabolite (2-oxo-3-OH-LSD) with simultaneous separation of structural isomers. Biological samples were prepared using liquid–liquid extraction (LLE) at pH 9 (with ethyl acetate); quantification was performed in multiple reaction monitoring (MRM) mode. LSD-d₃ was used as an internal standard. The limit of quantification (LOQ) for all substances was 0.5 pg mL⁻¹. Precision and accuracy did not exceed 15.8% and ±14.4%, respectively. Recovery and matrix effect values were 80.6–118.6% and ±19.4%. A stability study was conducted over 30 days under different storage conditions (25 °C, 4 °C and −20 °C) for blood, urine, plasma, and serum, collected in various test tube configurations and with different preservative agents. It was found that the collection of samples in NaF can effectively stabilize LSD analogs and minimize the conversion of N1-substituted compounds to LSD or MiPLA. The presented method is the most sensitive to date for analyzing designer LSD analogs in biological samples, with potential for routine clinical and forensic use, enhancing detection of emerging illicit compounds. By examining the mass spectra (QTOF-MS/MS) obtained in this study and reviewing the literature on analytical characterization of LSD analogs, we proposed fragmentation patterns to aid in future identification of new designer LSD analogs (NPS).

中文翻译：

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一种高灵敏度的 UHPLC-MS/MS 方法，用于测定生物样品中的 15 种设计 LSD 类似物，并应用于稳定性研究


近年来，非法药物市场中 LSD 类似物的合成和分销增加，通常被称为 “设计师迷幻药”，导致娱乐使用增加。这一趋势导致全球报告数量不断增加，执法部门越来越多地在吸墨纸和生物样品中检测到这些化合物。在本文中，开发了一种 UHPLC-Qq-MS/MS 方法，用于测定 LSD、其设计类似物（ALD-52、AL-LAD、LAMPA、LSM-775、LSZ、MiPLA、1B-LSD、1cP-LSD、1cP-MiPLA、1P-LSD、1P-MiPLA、1V-LSD 和 2-溴-LSD）及其代谢物（2-氧代-3-OH-LSD）及其代谢物 （2-氧代-3-OH-LSD） 的痕量 （fg ^mL-1），同时分离结构异构体。使用 pH 值为 9 的液-液萃取 （LLE）（使用乙酸乙酯）制备生物样品;在多反应监测 （MRM） 模式下进行定量。以 LSD-d₃ 为内标。所有物质的定量限 （LOQ） 为 0.5 pg mL⁻¹。精密度和准确度分别不超过 15.8% 和 ±14.4%。回收率和基质效应值分别为 80.6–118.6% 和 ±19.4%。在不同储存条件（25 °C、4 °C 和 -20 °C）下，对血液、尿液、血浆和血清进行了 30 天的稳定性研究，这些血液、尿液、血浆和血清收集在各种试管配置和不同的防腐剂中收集。研究发现，在 NaF 中收集样品可以有效稳定 LSD 类似物，并最大限度地减少 N1-取代化合物向 LSD 或 MiPLA 的转化。所提出的方法对于分析生物样本中的设计师 LSD 类似物是迄今为止最敏感的，具有常规临床和法医用途的潜力，可增强对新出现的非法化合物的检测。 通过检查本研究中获得的质谱 （QTOF-MS/MS） 并回顾有关 LSD 类似物分析表征的文献，我们提出了碎裂模式，以帮助将来鉴定新的设计 LSD 类似物 （NPS）。