Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man

• Published in: Pharmaceutica acta Helvetiae 1997-06, Vol.72 (3), p.175-184
• Main Authors: Hasler, F., Bourquin, D., Brenneisen, R., Bär, T., Vollenweider, F.X.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Chromatography, High Pressure Liquid; Electrochemistry; Female; Hallucinogens - administration & dosage; Hallucinogens - blood; Hallucinogens - pharmacokinetics; HPLC-ECD; Humans; Hydroxyindoleacetic Acid - blood; Injections, Intravenous; Male; Pharmacokinetics; Psilocin; Psilocybin; Psilocybin - administration & dosage; Psilocybin - analogs & derivatives; Psilocybin - blood; Psilocybin - pharmacokinetics
• ISSN: 0031-6865
• DOI: 10.1016/S0031-6865(97)00014-9

In order to investigate the pharmacokinetic properties of psilocybin (PY), the main psychoactive compound of Psilocybe mushrooms, high performance liquid chromatographic procedures with column-switching coupled with electrochemical detection (HPLC-ECD) for reliable quantitative determination of the PY metabolites psilocin (PI) and 4-hydroxyindole-3-acetic acid (4HIAA) in human plasma were established. Sample work-up includes protection of the highly unstable phenolic analytes with ascorbic acid, freeze-drying and in-vitro microdialysis. The data of two controlled clinical studies with healthy volunteers are presented. The subjects (N = 6 for both studies) received single oral PY doses of 0.224 ± 0.02 mg/kg b.wt. (10–20 mg) and intravenous doses of 1 mg PY, respectively. Peak plasma levels of PI after oral administration of PY were measured after 105 ± 37 min showing an average concentration of 8.2 ± 2.8 ng PI/ml plasma. 4HIAA peak concentrations of 150 ± 61 ng/ml plasma were found 113 ± 41 min after ingestion of PY. After intravenous administration, a mean PI maximum plasma concentration of 12.9 ± 5.6 ng/ml plasma was found 1.9 ± 1.0 min after injection. The maximum plasma levels appearing within a very short period indicate a rapid dephosphorylation of PY also when administered systemically. 4HIAA was not detected after 1 mg of intravenous PY. Estimates for the absolute bioavailability of PI after oral administration of PY were 52.7 ± 20% (N = 3).