A highly sensitive UHPLC-MS/MS method for determining 15 designer LSD analogs in biological samples with application to stability studies.
The Analyst – January 13, 2025
Source: PubMed
Summary
Scientists have developed a groundbreaking method to detect minute traces of LSD and its designer variants in blood and urine samples. The technique is so sensitive it can identify quantities as small as 0.5 picograms - that's smaller than one trillionth of a gram. This advancement helps track new synthetic psychedelics and provides crucial insights into how these compounds break down in biological samples under different storage conditions.
Abstract
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).