Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man.
Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man.
复制标题
DOI：
10.1016/s0031-6865(97)00014-9
复制
发表时间：
1997-06-01
期刊：
影响因子：
--
通讯作者：
Vollenweider, F X
中科院分区：
文献类型：
--
作者：
Hasler, F;Bourquin, D;Vollenweider, F X
为研究裸盖菇中主要精神活性物质裸盖菇素（Psilocybin，PY）的药代动力学特征，建立了人血浆中PY代谢物裸盖菇素（Psilocin，PI）和4-羟基吲哚-3-乙酸（4-hydroxyindole-3-acetate，4 HIAA）的高效液相色谱-电化学检测（HPLC-ECD）定量分析方法。样品处理包括用抗坏血酸保护高度不稳定的酚类分析物，冷冻干燥和体外微透析。提供了两项健康志愿者对照临床研究的数据。受试者（两项研究均为N = 6）接受0.224 +/- 0.02 mg/kg b.wt. PY单次口服给药。（10-20 mg）和静脉给药1 mg PY。在口服PY后105 +/- 37分钟后测量PI的峰值血浆水平，显示平均浓度为8.2 +/- 2.8 ng PI/ml血浆。4在摄入PY后113 ± 41分钟发现HIAA血浆峰浓度为150 ± 61 ng/ml。静脉给药后，在注射后1.9 +/- 1.0 min发现平均PI最大血浆浓度为12.9 +/- 5.6 ng/ml血浆。在非常短的时间内出现的最大血浆水平表明，当全身给药时，PY也会快速去磷酸化。4PY 1 mg静注后未检出HIAA。口服PY后PI的绝对生物利用度估计值为52.7 ± 20%（N = 3）。
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).