Modification of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method targeting lysergic acid diethylamide (LSD) and its primary metabolite (OH-LSD) to include nine LSD analogs
Corresponding Author
Amy L. Patton MS
Division of Forensic Toxicology, Armed Forces Medical Examiner System, Dover, Delaware, USA
SNA International, LLC, Contractor Supporting the Armed Forces Medical Examiner System, Alexandria, Virginia, USA
Correspondence
Amy L. Patton, Division of Forensic Toxicology, Armed Forces Medical Examiner System, 115 Purple Heart Drive, Dover AFB, DE 19902, USA.
Email: [email protected]
Search for more papers by this authorErin L. Karschner PhD
Division of Forensic Toxicology, Armed Forces Medical Examiner System, Dover, Delaware, USA
Search for more papers by this authorJeffrey P. Walterscheid PhD
Division of Forensic Toxicology, Armed Forces Medical Examiner System, Dover, Delaware, USA
Search for more papers by this authorJason M. Garcia PhD
Division of Forensic Toxicology, Armed Forces Medical Examiner System, Dover, Delaware, USA
Search for more papers by this authorCorresponding Author
Amy L. Patton MS
Division of Forensic Toxicology, Armed Forces Medical Examiner System, Dover, Delaware, USA
SNA International, LLC, Contractor Supporting the Armed Forces Medical Examiner System, Alexandria, Virginia, USA
Correspondence
Amy L. Patton, Division of Forensic Toxicology, Armed Forces Medical Examiner System, 115 Purple Heart Drive, Dover AFB, DE 19902, USA.
Email: [email protected]
Search for more papers by this authorErin L. Karschner PhD
Division of Forensic Toxicology, Armed Forces Medical Examiner System, Dover, Delaware, USA
Search for more papers by this authorJeffrey P. Walterscheid PhD
Division of Forensic Toxicology, Armed Forces Medical Examiner System, Dover, Delaware, USA
Search for more papers by this authorJason M. Garcia PhD
Division of Forensic Toxicology, Armed Forces Medical Examiner System, Dover, Delaware, USA
Search for more papers by this authorAbstract
A variety of LSD analogs have emerged in recent years with dual purposes of avoiding prosecution from possession while providing new options for those willing to experiment with hallucinogenic drugs. In this study, a previously published automated sample preparation method for LSD and its primary metabolite (OH-LSD) was utilized to extract LSD, OH-LSD, and nine LSD analogs from urine. The liquid chromatography tandem mass spectrometry (LC–MS/MS) method was modified from the previously published LC conditions to utilize a different analytical column and gradient elution program. Mobile phases of 10 mM ammonium formate with 0.1% formic acid in deionized water (mobile phase A) and 0.1% formic acid in methanol (mobile phase B) were employed. The method was validated to ANSI/ASB Standard 036 with a 0.1 ng/mL limit of detection for all analytes and was utilized for the analysis of 325 urine specimens. Although no LSD analogs were observed in the samples analyzed, this validated method was demonstrated to be suitable for the analysis of these compounds in laboratories seeking to expand their testing scope. Automated sample preparation allows for the efficient analysis of these analytically challenging compounds with minimal manual handling. Additionally, there was no increased analytical time burden when the LC column and gradient were modified to target nine additional analytes. Detection may improve as new reference standards are developed to allow laboratories to focus on the metabolic products of these analogs. For now, this validated procedure can assist with the routine analysis and surveillance of these emerging substances.
CONFLICT OF INTEREST STATEMENT
The authors have no conflicts of interest to report.
REFERENCES
- 1Nichols DE. Dark classics in chemical neuroscience: lysergic acid diethylamide (LSD). ACS Chem Neurosci. 2018; 9(10): 2331–2343. https://doi.org/10.1021/acschemneuro.8b00043
- 2Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A. The pharmacology of lysergic acid diethylamide: a review. CNS Neurosci Ther. 2008; 14(4): 295–314. https://doi.org/10.1111/j.1755-5949.2008.00059.x
- 3 Drug Enforcement Agency. LSD drug fact sheet. [cited 2024 Feb 25]. Available from: https://www.dea.gov/sites/default/files/2020-06/LSD-2020_0.pdf
- 4Bender L, Goldschmidt L, Sankar D, Freedman AM. Treatment of autistic schizophrenic children with LSD-25 and UML-491. Recent Adv Biol Psychiatry. 1961; 4: 170–179. https://doi.org/10.1007/978-1-4684-8306-2_17
- 5De Gregorio D, Comai S, Posa L, Gobbi G. d-lysergic acid diethylamide (LSD) as a model of psychosis: mechanism of action and pharmacology. Int J Mol Sci. 2016; 17(11):1953. https://doi.org/10.3390/ijms17111953
- 6Sigafoos J, Green VA, Edrisinha C, Lancioni GE. Flashback to the 1960s: LSD in the treatment of autism. Dev Neurorehabil. 2007; 10(1): 75–81. https://doi.org/10.1080/13638490601106277
- 7Smart RG, Storm T. The efficacy of LSD in the treatment of alcoholism. Q J Stud Alcohol. 1964; 25(2): 333–338. https://doi.org/10.15288/qjsa.1964.25.333
- 8Bonson KR. Regulation of human research with LSD in the United States (1949-1987). Psychopharmacology. 2018; 235(2): 591–604. https://doi.org/10.1007/s00213-017-4777-4
- 9Lewis V, Bonniwell EM, Lanham JK, Ghaffari A, Sheshbaradaran H, Cao AB, et al. A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Cell Rep. 2023; 42(3):112203. https://doi.org/10.1016/j.celrep.2023.112203
- 10Nuwer R. Americans increase LSD use—and a bleak outlook for the world may be to blame. [cited 2024 Feb 25]. Available from: https://www.scientificamerican.com/article/americans-increase-lsd-use-and-a-bleak-outlook-for-the-world-may-be-to-blame1/
- 11Palamar JJ, Acosta P, Sherman S, Ompad DC, Cleland CM. Self-reported use of novel psychoactive substances among attendees of electronic dance music venues. Am J Drug Alcohol Abuse. 2016; 42(6): 624–632. https://doi.org/10.1016/j.drugpo.2016.10.020
- 12Van Hout MC, Hearne E. New psychoactive substances (NPS) on cryptomarket fora: an exploratory study of characteristics of forum activity between NPS buyers and vendors. Int J Drug Policy. 2017; 40: 102–110. https://doi.org/10.1016/j.drugpo.2016.11.007
- 13Svenningsson P, Nairn AC, Greengard P. DARPP-32 mediates the actions of multiple drugs of abuse. AAPS J. 2005; 7(2): E353–E360. https://doi.org/10.1208/aapsj070235
- 14Carhart-Harris RL, Kaelen M, Bolstridge M, Williams TM, Williams LT, Underwood R, et al. The paradoxical psychological effects of lysergic acid diethylamide (LSD). Psychol Med. 2016; 46(7): 1379–1390. https://doi.org/10.1017/S0033291715002901
- 15Schmid Y, Enzler F, Gasser P, Grouzmann E, Preller KH, Vollenweider FX, et al. Acute effects of lysergic acid diethylamide in healthy subjects. Biol Psychiatry. 2015; 78(8): 544–553. https://doi.org/10.1016/j.biopsych.2014.11.015
- 16Hoffman AJ, Nichols DE. Synthesis and LSD-like discriminative stimulus properties in a series of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives. J Med Chem. 1985; 28(9): 1252–1255. https://doi.org/10.1021/jm00147a022
- 17Klette KL, Anderson CJ, Poch GK, Nimrod AC, ElSohly MA. Metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy LSD (O-H-LSD) in human liver microsomes and cryopreserved human hepatocytes. J Anal Toxicol. 2000; 24(7): 550–556. https://doi.org/10.1093/jat/24.7.550
- 18Libanio Osorio Marta RF. Metabolism of lysergic acid diethylamide (LSD): an update. Drug Metab Rev. 2019; 51(3): 378–387. https://doi.org/10.1080/03602532.2019.1638931
- 19Brandt SD, Kavanagh PV, Westphal F, Elliott SP, Wallach J, Colestock T, et al. Return of the lysergamides. Part II: analytical and behavioral characterization of N6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2'S,4'S)-lysergic acid 2,4-dimethylazetidide (LSZ). Drug Test Anal. 2017; 9: 38–50. https://doi.org/10.1002/dta.1985
- 20Zhang SH, Tang ASY, Chin RSL, Goh JY, Ong MC, Lim WJL, et al. Stability studies of ALD-52 and its homologue 1P-LSD. J Forensic Sci. 2023; 68(3): 1009–1019. https://doi.org/10.1111/1556-4029.15224
- 21Brandt SD, Kavanagh PV, Westphal F, Stratford A, Elliott SP, Hoang K, et al. Return of the lysergamides. Part I: analytical and behavioral characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD). Drug Test Anal. 2016; 8: 891–902. https://doi.org/10.1002/dta.1884
- 22Wagmann L, Richter LHJ, Kehl T, Wack F, Bergstrand MP, Brandt SD, et al. In vitro metabolic fate of nine LSD-based new psychoactive substances and their analytical detectability in different urinary screening procedures. Anal Bioanal Chem. 2019; 411(19): 4751–4763. https://doi.org/10.1007/s00216-018-1558-9
- 23Halberstadt AL, Chatha M, Klein AK, McCorvy JD, Meyer MR, Wagmann L, et al. Pharmacological and biotransformation studies of 1-acyl-substituted derivatives of d-lysergic acid diethylamide (LSD). Neuropharmacology. 2020; 172:107856. https://doi.org/10.1016/j.neuropharm.2019.107856
- 24Brandt SD, Kavanagh PV, Westphal F, Stratford A, Elliott SP, Dowling G, et al. Return of the lysergamides. Part V: analytical and behavioural characterization of 1-butanoyl-d-lysergic acid diethylamide (1B-LSD). Drug Test Anal. 2019; 11(8): 1122–1133. https://doi.org/10.1002/dta.2613
- 25Brandt SD, Kavanagh PV, Westphal F, Stratford A, Odland AU, Klein AK, et al. Return of the lysergamides. Part VI: analytical and behavioural characterization of 1-cyclopropanoyl-d-lysergic acid diethylamide (1CP-LSD). Drug Test Anal. 2020; 12(6): 812–826. https://doi.org/10.1002/dta.2789
- 26Tanaka R, Kawamura M, Mizutani S, Kikura-Hanajiri R. Identification of LSD analogs, 1cP-AL-LAD, 1cP-MIPLA, 1V-LSD and LSZ in sheet products. Forensic Toxicol. 2023; 41(2): 294–303. https://doi.org/10.1007/s11419-023-00661-1
- 27Patton AL, Brown J, Heine K, Sartori DA, Karschner EL, Walterscheid JP. Quantitative analysis of lysergic acid diethylamide and metabolite in urine by automated extraction and liquid chromatography–tandem mass spectrometry. J Anal Toxicol. 2023; 47(5): 448–454. https://doi.org/10.1093/jat/bkad012
- 28Pietsch J, Schulz K, Körner B, Trauer H, Dreßler J, Gey M. Alternative method for forensic determination of lysergic acid diethylamide and related compounds in body fluids by liquid–liquid extraction and HPLC with fluorescence detection. Chromatographia. 2004; 60(1/2): 89–92. https://doi.org/10.1365/s10337-004-0344-3
- 29Cody JT, Valtier S. Immunoassay analysis of lysergic acid diethylamide. J Anal Toxicol. 1997; 21(6): 459–464. https://doi.org/10.1093/jat/21.6.459
- 30 AAFS Standards Board. ANSI/ASB standard 036: standard practices for method validation in forensic toxicology. Colorado Springs, CO: AAFS Standards Board; 2019.
- 31 Office of the Under Secretary of Defense for Personnel and Readiness. DoD instruction 1010.16: technical procedures for the military drug abuse testing program. Washington, DC: Office of the Under Secretary of Defense for Personnel and Readiness; 2020.
- 32Francom P, Andrenyak D, Lim H-K, Bridges RR, Foltz RL, Jones RT. Determination of LSD in urine by capillary column gas chromatography and electron impact mass spectrometry. J Anal Toxicol. 1988; 12(1): 1–8. https://doi.org/10.1093/jat/12.1.1
- 33Li Z, McNally AJ, Wang H, Salamone SJ. Stability study of LSD under various storage conditions. J Anal Toxicol. 1998; 22(6): 520–525. https://doi.org/10.1093/jat/22.6.520
- 34Brandt SD, Kavanagh PV, Westphal F, Pulver B, Schwelm H, Whitelock K, et al. Analytical profile, in vitro metabolism and behavioral properties of the lysergamide 1P-AL-LAD. Drug Test Anal. 2022; 14(8): 1503–1518. https://doi.org/10.1002/dta.3281
- 35Beharry S, Gibbons S. An overview of emerging and new psychoactive substances in the United Kingdom. Forensic Sci Int. 2016; 267: 25–34. https://doi.org/10.1016/j.forsciint.2016.08.013
- 36Coney LD, Maier LJ, Ferris JA, Winstock AR, Barratt MJ. Genie in a blotter: a comparative study of LSD and LSD analogues' effects and user profile. Hum Psychopharmacol. 2017; 32(3):e2599. https://doi.org/10.1002/hup.2599
- 37Bynum ND, Moore KN, Grabenauer M. Evaluation of laser diode thermal desorption-tandem mass spectrometry (LDTD-MS-MS) in forensic toxicology. J Anal Toxicol. 2014; 38(8): 528–535. https://doi.org/10.1093/jat/bku084
- 38Mogollón NGS, Quiroz-Moreno CD, Prata PS, de Almeida JR, Cevallos AS, Torres-Guiérrez R, et al. New advances in toxicological forensic analysis using mass spectrometry techniques. J Anal Methods Chem. 2018; 2018:4142527. https://doi.org/10.1155/2018/4142527
- 39Poch GK, Klette KL, Hallare DA, Manglicmot MG, Czarny RJ, McWhorter LK, et al. Detection of metabolites of lysergic acid diethylamide (LSD) in human urine specimens: 2-oxo-3-hydroxy-LSD, a prevalent metabolite of LSD. J Chromatogr B Biomed Appl. 1999; 724(1): 23–33. https://doi.org/10.1016/S0378-4347(98)00574-X
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