Validation of an LC-MS/MS method for the quantitative analysis of 1P-LSD and its tentative metabolite LSD in fortified urine and serum samples including stability tests for 1P-LSD under different storage conditions

Grumann, Christina; Henkel, Kerstin; Stratford, Alexander; Hermanns-Clausen, Maren; Passie, Torsten; Brandt, Simon D.; Auwärter, Volker

doi:10.1016/j.jpba.2019.05.062

Cited by 21 publications

(29 citation statements)

References 16 publications

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“…It has since been confirmed that the 1‐acyl substituted lysergamides ALD‐52, 1P‐LSD, 1P‐ETH‐LAD, and 1B‐LSD were indeed transformed into LSD and ETH‐LAD, respectively 22,24 . These findings were also consistent with the data reported in an intoxication where the ingestion of 1P‐LSD in blotter form did not result in its detection in either urine or serum but LSD instead 23 . In the present investigation, an incubation of 1CP‐LSD with human serum also revealed the formation of LSD when the incubation mixture was analyzed by LC‐ESI single quadrupole MS. As summarized in the Supporting Information section (analyses performed in triplicate but only one representative example shown), it was found that the signal response related to the hydrolysis product increased over time when analyzed at 0, 1, 2, 3, 5, 7, and 24 h. These results showed that 1CP‐LSD was hydrolyzed to LSD in serum but that conversion was not complete within the first 24 h. However, 1CP‐LSD is likely to be hydrolyzed at a much faster rate in vivo because humans express carboxyesterase in red blood cell membranes but not in serum 37,38 .…”

Section: Resultssupporting

confidence: 86%

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Return of the lysergamides. Part VI: Analytical and behavioural characterization of 1‐cyclopropanoyl‐d‐lysergic acid diethylamide (1CP‐LSD)

Brandt

Kavanagh

Westphal³

et al. 2020

Drug Testing and Analysis

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Lysergic acid diethylamide (LSD) is a prototypical serotonergic psychedelic drug and the subject of many clinical investigations. In recent years, a range of lysergamides has emerged with the production of some being inspired by the existing scientific literature. Others, for example various 1‐acyl substituted lysergamides, did not exist before their appearance as research chemicals. 1‐Cylopropanoyl‐LSD (1CP‐LSD) has recently emerged as a new addition to the group of lysergamide‐based designer drugs and is believed to be psychoactive in humans. In this investigation, 1CP‐LSD was subjected to detailed analytical characterizations including various mass spectrometry (MS) platforms, gas and liquid chromatography, nuclear magnetic resonance spectroscopy, solid phase and GC condensed phase infrared spectroscopy. Analysis by GC–MS also revealed the detection of artificially induced degradation products. Incubation of 1CP‐LSD with human serum led to the formation of LSD, indicating that it may act as a prodrug for LSD in vivo, similar to other 1‐acyl substituted lysergamides. The analysis of blotters and pellets is also included. 1CP‐LSD also induces the head‐twitch response (HTR) in C57BL/6 J mice, indicating that it produces an LSD‐like behavioural profile. 1CP‐LSD induced the HTR with an ED50 = 430.0 nmol/kg which was comparable to 1P‐LSD (ED50 = 349.6 nmol/kg) investigated previously. Clinical studies are required to determine the potency and profile of the effects produced by 1CP‐LSD in humans.

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Section: Resultssupporting

confidence: 86%

“…It was shown recently that 1‐acylated lysergamides likely serve as prodrugs to either LSD (1P‐LSD, 1B‐LSD, ALD‐52) 18,19,22–24 or N 6 ‐ethyl‐nor‐LSD (ETH‐LAD) (from 1P‐ETH‐LAD), 19,22 suggesting that the detection of the parent 1‐acylated lysergamide in vivo following ingestion might be challenging.…”

Section: Introductionmentioning

confidence: 99%

Return of the lysergamides. Part VI: Analytical and behavioural characterization of 1‐cyclopropanoyl‐d‐lysergic acid diethylamide (1CP‐LSD)

Brandt

Kavanagh

Westphal³

et al. 2020

Drug Testing and Analysis

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“…Little is known about the adverse effects of lysergamide designer drugs. One case of a 17-year-old male who developed anxiety, hallucinations, restlessness, elevations of blood pressure, palpitations, and tachycardia after ingesting 1P-LSD was reported (Grumann et al 2019). 1P-LSD was confirmed as an ingredient of the ingested blotter paper but could not be detected in urine or serum samples, despite being sufficiently stable in these matrices.…”

Section: Adverse Effects Of Lysergamidesmentioning

confidence: 99%

Designer drugs: mechanism of action and adverse effects

2020

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Psychoactive substances with chemical structures or pharmacological profiles that are similar to traditional drugs of abuse continue to emerge on the recreational drug market. Internet vendors may at least temporarily sell these so-called designer drugs without adhering to legal statutes or facing legal consequences. Overall, the mechanism of action and adverse effects of designer drugs are similar to traditional drugs of abuse. Stimulants, such as amphetamines and cathinones, primarily interact with monoamine transporters and mostly induce sympathomimetic adverse effects. Agonism at l-opioid receptors and c-aminobutyric acid-A (GABA A) or GABA B receptors mediates the pharmacological effects of sedatives, which may induce cardiorespiratory depression. Dissociative designer drugs primarily act as N-methyl-D-aspartate receptor antagonists and pose similar health risks as the medically approved dissociative anesthetic ketamine. The cannabinoid type 1 (CB 1) receptor is thought to drive the psychoactive effects of synthetic cannabinoids, which are associated with a less desirable effect profile and more severe adverse effects compared with cannabis. Serotonergic 5-hydroxytryptamine-2A (5-HT 2A) receptors mediate alterations of perception and cognition that are induced by serotonergic psychedelics. Because of their novelty, designer drugs may remain undetected by routine drug screening, thus hampering evaluations of adverse effects. Intoxication reports suggest that several designer drugs are used concurrently, posing a high risk for severe adverse effects and even death.

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“…Recently, a number of LSD derivatives and analogues have been investigated, namely 1‐acetyl‐LSD (1A‐LSD, ALD‐52), 1‐propanoyl‐LSD (1P‐LSD), 1‐butanoyl‐LSD (1B‐LSD), N 6 ‐ethyl‐nor‐LSD (ETH‐LAD), 1‐propanoyl‐ N 6 ‐ethyl‐nor‐LSD (1P‐ETH‐LAD), N 6 ‐allyl‐nor‐LSD (AL‐LAD), N ‐ethyl‐ N ‐cyclopropyl lysergamide (ECPLA), (2′ S ,4′S)‐lysergic acid 2,4‐dimethylazetidide (LSZ), and lysergic acid morpholide (LSM‐775) (Fig. B ).…”

Section: Prodrugs Of Psychoactive Substancesmentioning

confidence: 99%

“…B ). A biotransformation has been observed in lysergamides acylated at the indole nitrogen that in turn produces the corresponding “core” drug of LSD or ETH‐LAD . Therefore, 1P‐LSD, 1B‐LSD, and ALD‐52 are all prodrugs of LSD and 1P‐ETH‐LAD is a prodrug of ETH‐LAD.…”

Section: Prodrugs Of Psychoactive Substancesmentioning

confidence: 99%

Prodrugs of New Psychoactive Substances (NPS): A New Challenge

Elliott

Holdbrook

Brandt

2020

Journal of Forensic Sciences

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The concept of a substance acting as a prodrug for an intended drug is not new and has been known and utilized with particular benefits within medicine for efficacy and patient safety. Prodrugs of psychoactive substances are also not particularly new but this has also extended to considerations of prodrugs of new psychoactive substances (NPS). The continuing evolution of NPS has been a constant forensic challenge. In some countries, this constant evolution has led to the introduction of various alternative methods of drug control. Whether for this reason or in the pursuit of user experimentation, prodrugs of NPS have been discussed, developed, and exploited, posing some distinct forensic challenges. This is especially the case within toxicological analysis of biological fluids and for some substances, also forensic chemical analysis, through inherent instability of the prodrug or metabolism in the body. Particular examples of NPS prodrugs include 1-propanoyl-LSD, 1-butanoyl-LSD, 1-acetyl-LSD, and 2C-B-AN. This is in addition to associated substances and medicines that may be used for an intended pharmacological effect. Various prodrugs for stimulant and hallucinogenic substances in particular have appeared in the literature and have been discussed within drug user forums and made available for purchase online. Presently, drug monitoring data from national and international systems indicate that prodrugs are not widely available or problematic. Nevertheless, it is important that there is sufficient awareness of the prodrug concept and potential impact and associated forensic implications, not just for chemical analysis but also for toxicological considerations when a substance has been used.

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Validation of an LC-MS/MS method for the quantitative analysis of 1P-LSD and its tentative metabolite LSD in fortified urine and serum samples including stability tests for 1P-LSD under different storage conditions

Abstract: Validation of an LC-MS/MS method for the quantitative analysis of 1P-LSD and its tentative metabolite LSD in fortified urine and serum samples including stability tests for 1P

Cited by 21 publications

References 16 publications

Return of the lysergamides. Part VI: Analytical and behavioural characterization of 1‐cyclopropanoyl‐d‐lysergic acid diethylamide (1CP‐LSD)

Return of the lysergamides. Part VI: Analytical and behavioural characterization of 1‐cyclopropanoyl‐d‐lysergic acid diethylamide (1CP‐LSD)

Designer drugs: mechanism of action and adverse effects

Prodrugs of New Psychoactive Substances (NPS): A New Challenge

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