Quantification of psilocin in human whole blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

forensic toxicology hallucinogen liquid chromatography-tandem mass spectrometry and LC-MS/MS psilocin in human whole blood psilocybin

Journal

Journal of forensic sciences
ISSN: 1556-4029
Titre abrégé: J Forensic Sci
Pays: United States
ID NLM: 0375370

Informations de publication

Date de publication:
22 Dec 2023
Historique:
revised: 13 11 2023
received: 12 10 2023
accepted: 12 12 2023
medline: 23 12 2023
pubmed: 23 12 2023
entrez: 23 12 2023
Statut: aheadofprint

Résumé

There has been burgeoning interest in psilocybin-use for the treatment of various neurological and neurodegenerative diseases. Psilocybin is mistakenly perceived as the principal pharmacologically active compound due to its high concentrations found in magic mushrooms; however, it is the prodrug of psilocin. Despite the expanding body of clinical research seeking to understand the pharmacodynamic/pharmacokinetic properties of psilocin, and its role in inducing dramatic changes to cognitive function, there has not been a corresponding increase in the development of sensitive analytical methods that can quantify psilocin in different biological fluids. Existing analytical methods have been developed using plasma, serum, and urine as the matrix of choice, but with the unknown blood-to-plasma ratio of psilocin, any pharmacokinetic conclusions drawn solely on plasma data may be misleading. Thus, the main objective of this study is to develop the first analytical method that utilizes SPE and LC-MS/MS to quantify psilocin in human whole blood. The SPE procedure yielded a high recovery efficiency (≥89%) with minimal matrix effects. The method was validated according to ANSI/ASB 036 guidelines. Linearity was between 0.7-200 ng/mL and encompassed previously reported ranges found in plasma/serum. Bias, within- and between-run precision for all quality controls met ANSI/ASB 036 acceptability criteria. Endogenous/exogenous interferences and carryover were negligible. Psilocin stability was assessed at 4°C over 48 h and was considered stable. Although a proof-of-concept study will need to be performed to characterize the method, this analytical workflow was able to detect and quantify psilocin in human whole blood at low limits of quantification.

Identifiants

pubmed: 38140718
doi: 10.1111/1556-4029.15454
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2023 American Academy of Forensic Sciences.

Références

Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol. 2016;30(12):1181-1197. https://doi.org/10.1177/0269881116675513
Fuentes JJ, Fonseca F, Elices M, Farré M, Torrens M. Therapeutic use of LSD in psychiatry: a systematic review of randomized-controlled clinical trials. Front Psych. 2020;10:943. https://doi.org/10.3389/fpsyt.2019.00943
dos Santos RG, Osório FL, Crippa JAS, Riba J, Zuardi AW, Hallak JEC. Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years: Antidepressive effects of ayahuasca, psilocybin and LSD. Ther Adv Psychopharmacol. 2016;6(3):193-213. https://doi.org/10.1177/2045125316638008
Kuypers KPC. The therapeutic potential of microdosing psychedelics in depression. Ther Adv Psychopharmacol. 2020;10:204512532095056. https://doi.org/10.1177/2045125320950567
Hofmann A, Heim R, Brack A, Kobel H, Frey A, Ott H, et al. Psilocybin und psilocin, zwei psychotrope Wirkstoffe aus mexikanischen Rauschpilzen [psilocybin and psilocin, two psychotropic compounds from mexican intoxicating mushrooms]. Helv Chim Acta. 1959;42(5):1557-1572. https://doi.org/10.1002/hlca.19590420518
Nichols DE. Hallucinogens. Pharmacol Ther. 2004;101(2):131-181. https://doi.org/10.1016/j.pharmthera.2003.11.002
Araújo AM, Carvalho F, Bastos M d L, Guedes de Pinho P, Carvalho M. The hallucinogenic world of tryptamines: an updated review. Arch Toxicol. 2015;89(8):1151-1173. https://doi.org/10.1007/s00204-015-1513-x
Sewell RA, Halpern JH, Pope HG. Response of cluster headache to psilocybin and LSD. Neurology. 2006;66(12):1920-1922. https://doi.org/10.1212/01.wnl.0000219761.05466.43
Grob CS, Danforth AL, Chopra GS, Hagerty M, McKay CR, Halberstadt AL, et al. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry. 2011;68(1):71-78. https://doi.org/10.1001/archgenpsychiatry.2010.116
Bogenschutz MP, Podrebarac SK, Duane JH, Amegadzie SS, Malone TC, Owens LT, et al. Clinical interpretations of patient experience in a trial of psilocybin-assisted psychotherapy for alcohol use disorder. Front Pharmacol. 2018;9:100. https://doi.org/10.3389/fphar.2018.00100
Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016;30(12):1165-1180. https://doi.org/10.1177/0269881116675512
New York Times. Legal use of hallucinogenic mushrooms begins in Oregon. 2023. https://www.nytimes.com/2023/01/03/health/psychedelic-drugs-mushrooms-oregon.html. Accessed 15 May 2023
Passie T, Seifert J, Schneider U, Emrich HM. The pharmacology of psilocybin. Addict Biol. 2002;7(4):357-364. https://doi.org/10.1080/1355621021000005937
Hasler F, Bourquin D, Brenneisen R, Vollenweider FX. Renal excretion profiles of psilocin following oral administration of psilocybin: a controlled study in man. J Pharm Biomed Anal. 2002;30(2):331-339. https://doi.org/10.1016/S0731-7085(02)00278-9
Strumila R, Nobile B, Korsakova L, Lengvenyte A, Olie E, Lopez-Castroman J, et al. Psilocybin, a naturally occurring indoleamine compound, could be useful to prevent suicidal behaviors. Pharmaceuticals (Basel). 2021;14(12):1213. https://doi.org/10.3390/ph14121213
Kozlowska U, Nichols C, Wiatr K, Figiel M. From psychiatry to neurology: psychedelics as prospective therapeutics for neurodegenerative disorders. J Neurochem. 2022;162(1):89-108. https://doi.org/10.1111/jnc.15509
Hasler F, Bourquin D, Brenneisen R, Bär T, Vollenweider FX. Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man. Pharm Acta Helv. 1997;72(3):175-184. https://doi.org/10.1016/S0031-6865(97)00014-9
Lindenblatt H, Krämer E, Holzmann-Erens P, Gouzoulis-Mayfrank E, Kovar K-A. Quantitation of psilocin in human plasma by high-performance liquid chromatography and electrochemical detection: comparison of liquid-liquid extraction with automated on-line solid-phase extraction. J Chromatogr B Biomed Sci Appl. 1998;709(2):255-263. https://doi.org/10.1016/S0378-4347(98)00067-X
Sticht G, Käferstein H. Detection of psilocin in body fluids. Forensic Sci Int. 2000;113(1-3):403-407. https://doi.org/10.1016/S0379-0738(00)00213-9
Albers C, Köhler H, Lehr M, Brinkmann B, Beike J. Development of a psilocin immunoassay for serum and blood samples. Int J Leg Med. 2004;118(6):326-331. https://doi.org/10.1007/s00414-004-0469-9
Kamata T, Nishikawa M, Katagi M, Tsuchihashi H. Optimized glucuronide hydrolysis for the detection of psilocin in human urine samples. J Chromatogr B. 2003;796(2):421-427. https://doi.org/10.1016/j.jchromb.2003.08.030
Kamata T, Nishikawa M, Katagi M, Tsuchihashi H. Direct detection of serum psilocin glucuronide by LC/MS and LC/MS/MS: time-courses of total and free (unconjugated) psilocin concentrations in serum specimens of a “magic mushroom” user. Forensic Toxicol. 2006;24(1):36-40. https://doi.org/10.1007/s11419-006-0006-2
Björnstad K, Beck O, Helander A. A multi-component LC-MS/MS method for detection of ten plant-derived psychoactive substances in urine. J Chromatogr B. 2009;877(11-12):1162-1168. https://doi.org/10.1016/j.jchromb.2009.03.004
Del Mar Ramirez Fernandez M, Laloup M, Wood M, De Boeck G, Lopez-Rivadulla M, Wallemacq P, et al. Liquid chromatography-tandem mass spectrometry method for the simultaneous analysis of multiple hallucinogens, chlorpheniramine, ketamine, ritalinic acid, and metabolites, in urine. J Anal Toxicol. 2007;31(8):497-504. https://doi.org/10.1093/jat/31.8.497
Saito K, Toyo'oka T, Fukushima T, Kato M, Shirota O, Goda Y. Determination of psilocin in magic mushrooms and rat plasma by liquid chromatography with fluorimetry and electrospray ionization mass spectrometry. Anal Chim Acta. 2004;527(2):149-156. https://doi.org/10.1016/j.aca.2004.08.071
Kolaczynska KE, Liechti ME, Duthaler U. Development and validation of an LC-MS/MS method for the bioanalysis of psilocybin's main metabolites, psilocin and 4-hydroxyindole-3-acetic acid, in human plasma. J Chromatogr B. 2021;1164:122486. https://doi.org/10.1016/j.jchromb.2020.122486
Brown RT, Nicholas CR, Cozzi NV, Gassman MC, Cooper KM, Muller D, et al. Pharmacokinetics of escalating doses of oral psilocybin in healthy adults. Clin Pharmacokinet. 2017;56(12):1543-1554. https://doi.org/10.1007/s40262-017-0540-6
Martin R, Schürenkamp J, Pfeiffer H, Köhler H. A validated method for quantitation of psilocin in plasma by LC-MS/MS and study of stability. Int J Leg Med. 2012;126(6):845-849. https://doi.org/10.1007/s00414-011-0652-8
Grieshaber AF, Moore KA, Levine B. The detection of psilocin in human urine. J Forensic Sci. 2001;46:627-630. https://doi.org/10.1520/JFS15014J
Anastos N, Barnett NW, Pfeffer FM, Lewis SW. Investigation into the temporal stability of aqueous standard solutions of psilocin and psilocybin using high performance liquid chromatography. Sci Justice. 2006;46(2):91-96. https://doi.org/10.1016/S1355-0306(06)71579-9
Yockey A, King K. Use of psilocybin (“mushrooms”) among US adults: 2015-2018. J Psychedelic Stud. 2021;5(1):17-21. https://doi.org/10.1556/2054.2020.00159
Center for Behavioral Health Statistics and Quality. 2017 national survey on drug use and health: detailed tables. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2018.
Diversion Control Division. National Forensic Laboratory Information System: NFLIS-drug 2022 annual report. Washington, DC: U.S. Department of Justice, U.S. Drug Enforcement Administration; 2023.
Dinis-Oliveira RJ. Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. Drug Metab Rev. 2017;49(1):84-91. https://doi.org/10.1080/03602532.2016.1278228
MacCallum CA, Lo LA, Pistawka CA, Deol JK. Therapeutic use of psilocybin: practical considerations for dosing and administration. Front Psych. 2022;13:1040217. https://doi.org/10.3389/fpsyt.2022.1040217

Auteurs

Munchelou M Gomonit (MM)

Department of Forensic Science, College of Criminal Justice, Sam Houston State University, Huntsville, Texas, USA.

Britni Skillman (B)

Department of Forensic Science, College of Criminal Justice, Sam Houston State University, Huntsville, Texas, USA.

Madeleine J Swortwood (MJ)

Department of Forensic Science, College of Criminal Justice, Sam Houston State University, Huntsville, Texas, USA.
Robson Forensic, Denver, Colorado, USA.

Classifications MeSH