Separating the wheat from the chaff: Observations on the analysis of lysergamides LSD, MIPLA, and LAMPA

Abstract

Lysergic acid diethylamide (LSD) is a potent psychoactive substance that has attracted great interest in clinical research. As the pharmacological exploration of LSD analogs continues to grow, some of those analogs have appeared on the street market. Given that LSD analogs are uncontrolled in many jurisdictions, it is important that these analogs be differentiated from LSD. This report presents the analysis of blotters found to contain the N-methyl-N-isopropyl isomer of LSD (MIPLA), and techniques to differentiate it from LSD and the N-methyl-N-propyl isomer (LAMPA) under routine conditions. Gas chromatography (GC)-solid phase infrared spectroscopy was particularly helpful. GC-electron ionization-tandem mass spectrometry of the m/z 72 iminium ion also provided sufficient information to distinguish the three isomers on mass spectral grounds alone, where chromatographic separation proved challenging. Derivatization with 2,2,2-trifluoro-N,N-bis (trimethylsilyl)acetamide (BSTFA) also led to improved GC separation. Liquid chromatography single quadrupole mass spectrometry (LC-Q-MS) and in-source collision-induced dissociation allowed for the differentiation between MIPLA and LAMPA based on distinct m/z 239 ion ratios when co-eluting. An alternative LC-MS/MS method improved the separation between all three lysergamides, but LSD was found to co-elute with iso-LSD. However, a comparison of ion ratios recorded for transitions at m/z 324.2 > 223.2 and m/z 324.2 > 208.2 facilitated their differentiation. The analysis of two blotters by LC-Q-MS revealed the presence of 180 and 186 μg MIPLA per blotter. These procedures may be used to avoid inadvertent misidentification of MIPLA or LAMPA as LSD.

Addressing the challenges in forensic drug chemistry II

“…This question arose during the analysis of blotters expected to contain the N-methyl-N-isopropyl isomer of LSD (MIPLA). 21 the majority of methamphetamine samples consisted of (S)methamphetamine and some samples also revealed the presence of the (R)-enantiomer. 22…”

“…An example was reported by Brandt and colleagues who explored a variety of methods to differentiate between the three isomeric lysergamides LSD, MIPLA, and LAMPA. This question arose during the analysis of blotters expected to contain the N ‐methyl‐ N ‐isopropyl isomer of LSD (MIPLA) 21 . Increasing interest has emerged when it comes to the differentiation between enantiomeric substances, and this challenges was taken on by Losacker et al who report on the analysis of amphetamine ( n = 143), 3,4‐methylendioxy‐ N ‐methamphetamine (MDMA) ( n = 94), and methamphetamine ( n = 528) samples seized in southern Germany in 2019 and 2020.…”

Interpol Review of Drug Analysis 2019-2022

“…2020 Identification and analysis of LSD derivatives (4-Acetyl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg] quinoline-9-carboxamide (ALD-52), N,N,7-triethyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (ETH-LAD), 7-Allyl-N,N-diethyl-4,6,6a,7,8,9-hexahydroindolo[ 4,3-fg]quinoline-9-carboxamide (AL-LAD), N,N-diethyl-7- methyl-4-propionyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (1P-LSD)) in illegal paper sheet products by GC-MS, LC-MS, LC-Q-TOF-MS and NMR [ 155 ]; 2021 screening method of Lysergic Acid Diethylamide (LSD) in blotter papers using square wave voltammetry with a Boron-Doped Diamond Electrode (BDDE) [ 156 ]; cluster of cases involving laboratory-confirmed LSD in a powder that was sold as cocaine [ 157 ]; 2022 analysis of blotters found to contain the N-methyl-N-isopropyl isomer of LSD (MIPLA), and techniques to differentiate it from LSD and the N-methyl-N-propyl isomer (LAMPA) [ 158 ].…”

Analytical and behavioral characterization of N‐ethyl‐N‐isopropyllysergamide (EIPLA), an isomer of N6–ethylnorlysergic acid N,N‐diethylamide (ETH‐LAD)

“…5,6,[10][11][12][13][14][15] It appears that MIPLA is available on the research chemicals market based on its reported detection in blotter paper samples ("blotters"). 16,17 1-(Cyclopropanecarbonyl)-MIPLA (1cP-MIPLA), a potential prodrug for MIPLA, has also been detected in blotter paper products distributed on the research chemicals market. 18 N-Ethyl-6-methyl-N-(propan-2-yl)-9,10-didehydroergoline-8βcarboxamide (N-ethyl-N-isopropyllysergamide, EIPLA, Figure 1) is a MIPLA homolog that shows LSD-like properties both in vivo and in vitro.…”