The differentiation of LSD and its 17 related compounds by GC-EI-MS and GC-CI-QTOF-MS

Abstract

In recent years, the distribution of blotter paper-type products containing analogues of lysergic acid diethylamide (LSD) has increased globally. These compounds have two asymmetric carbons in their structures and a small amount of their stereoisomers (iso-forms) were detected in some products. In this study, the differentiation method of LSD and its 17 related compounds by GC-MS was investigated. Moreover, for a clearer differentiation by mass spectra, the analytical method for LSD, its structural isomers (MiPLA and LAMPA) and their stereoisomers (iso-LSD, iso-MiPLA and iso-LAMPA) was also investigated by GC-QTOF-MS. LSD, its 12 analogues (ALD-52, 1P-LSD, 1B-LSD, 1cP-LSD, ETH-LAD, AL-LAD, MiPLA, LAMPA, LSM-775, LSZ, 1cP-AL-LAD and 1V-LSD) and the 5 stereoisomers (iso-LSD, iso-MiPLA, iso-LAMPA, iso-LSZ and iso-ETH-LAD) were investigated in this study. They were used as acetonitrile or methanol solutions for the GC-MS and GC-QTOF-MS analyses. In the GC-EI-MS, LSD and the 17 related compounds were detected from 11 to 21 min using a DB-1HT column (15 m x 0.25 mm i.d., 0.10 μm, Agilent). Although the separation of these compounds was almost successful, it was difficult to differentiate LSD and its isomers without the reference materials due to their close retention times and identical EI mass spectra. It was observed that the N1-acylated LSD analogs, such as 1P-LSD, 1cP-LSD, 1B-LSD and 1V-LSD, were deacylated to LSD during the GC-MS analysis using methanol as a solvent. For a clearer differentiation of LSD, its structural isomers (MiPLA and LAMPA) and their stereoisomers (iso-LSD, iso-MiPLA and iso-LAMPA), GC-CI-QTOF-MS (reagent gas: methane) was investigated. The MS/MS measurements were performed using the fragment ion m/z 72.081 [C4H10 N]+ as the precursor ion for LSD, MiPLA and LAMPA, and their product ion spectra were compared. As a result, the three compounds could be clearly differentiated by the presence or absence of the product ion m/z 44.049 [C2H6 N]+ or m/z 56.049 [C3H6 N]+, which indicates the differences in their structures. The MS/MS measurements of the fragment ion m/z 128.107 [C7H14NO]+ also showed differences in the product ions. As in the case of the three LSD-structural isomers, iso-LSD, iso-MiPLA and iso-LAMPA could be differentiated by comparison with the product ion spectra. Furthermore, in the product ion spectra of [M + H]+ m/z 324.207, differences were observed between the LSD structural isomers and their stereoisomers. The above differences in the product ion spectra were detectable if a CI measurement is used, even if not by an accurate mass spectrometry. Simon B et al. (Simon D. Brandt et al., Drug Test Anal, 2021,14(3), 545–556) reported that LSD, MiPLA and LAMPA could be differentiated by product ion spectra from the fragment ion m/z 72 in GC-MS/MS EI measurements. However, in this study, the accurate mass spectrometry using GC-QTOFMS EI measurements revealed that two ions, m/z 72.081 [C4H10 N]+ and m/z 72.044 [C3H6NO]+ were detected for LSD, while only m/z 72.081 [C4H10 N]+ was detected for MiPLA and LAMPA. Therefore, in the GC-MS/MS EI measurement of LSD, the product ion spectrum obtained from m/z 72 could be a mixed spectrum generated from two ions, which might lead to confusion in considering the fragmentation. The GC-EI-MS differentiation method was shown for LSD and the 17 related compounds in this study. Moreover, LSD, its structural isomers (MiPLA and LAMPA) and their 3 stereoisomers, which were difficult to identify by GC-EI-MS without their reference materials, were clearly differentiated by the MS/MS measurements using m/z 72.081 [C4H10 N]+, m/z 128.107 [C7H14NO]+ and m/z 324.207 [M + H]+ as precursor ions in the GC-CI-QTOFMS.