The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Jogarao V S Gobburu - One of the best experts on this subject based on the ideXlab platform.
-
exposure response analysis to assess the concentration qtc relationship of psilocybin Psilocin
Clinical pharmacology in drug development, 2020Co-Authors: Elyes Dahmane, Paul R Hutson, Jogarao V S GobburuAbstract:Psilocybin is being developed for treating major depressive disorder. Psilocybin is readily dephosphorylated to Psilocin upon absorption. The potential for Psilocin proarrhythmic effect was assessed using a concentration-QTc interval (C-QTc) analysis from an open-label single ascending dose study of psilocybin. Psilocybin doses ranged from 0.3 to 0.6 mg/kg. This trial showed a significant but shallow C-QTc relationship. At the clinical dose of 25 mg, the mean Psilocin maximum concentration is 18.7 ng/mL, and the associated mean (upper 90% confidence interval of mean) QTcF change is 2.1 (6.6) milliseconds. Given the short half-life of Psilocin of about 4 hours, there would be no accumulation after monthly oral doses used in clinical trials. The upper limit of the 90% confidence interval of the model-predicted mean ΔQTcF crossed 10 milliseconds at a Psilocin concentration of 31.1 ng/mL. At a supraclinical Psilocin maximum concentration of about 60 ng/mL, ΔQTcF remains low, with a mean (upper limit of the 90% confidence interval) of 9.1 (17.9) milliseconds. This analysis enabled the characterization of the C-QTc relationship and prediction of QTc prolongation at the expected clinical and possible higher psilocybin doses.
-
Exposure‐Response Analysis to Assess the Concentration‐QTc Relationship of Psilocybin/Psilocin
Clinical pharmacology in drug development, 2020Co-Authors: Elyes Dahmane, Paul R Hutson, Jogarao V S GobburuAbstract:Psilocybin is being developed for treating major depressive disorder. Psilocybin is readily dephosphorylated to Psilocin upon absorption. The potential for Psilocin proarrhythmic effect was assessed using a concentration-QTc interval (C-QTc) analysis from an open-label single ascending dose study of psilocybin. Psilocybin doses ranged from 0.3 to 0.6 mg/kg. This trial showed a significant but shallow C-QTc relationship. At the clinical dose of 25 mg, the mean Psilocin maximum concentration is 18.7 ng/mL, and the associated mean (upper 90% confidence interval of mean) QTcF change is 2.1 (6.6) milliseconds. Given the short half-life of Psilocin of about 4 hours, there would be no accumulation after monthly oral doses used in clinical trials. The upper limit of the 90% confidence interval of the model-predicted mean ΔQTcF crossed 10 milliseconds at a Psilocin concentration of 31.1 ng/mL. At a supraclinical Psilocin maximum concentration of about 60 ng/mL, ΔQTcF remains low, with a mean (upper limit of the 90% confidence interval) of 9.1 (17.9) milliseconds. This analysis enabled the characterization of the C-QTc relationship and prediction of QTc prolongation at the expected clinical and possible higher psilocybin doses.
Nicole Anastos - One of the best experts on this subject based on the ideXlab platform.
-
Investigation into the temporal stability of aqueous standard solutions of Psilocin and psilocybin using high performance liquid chromatography
Science & justice : journal of the Forensic Science Society, 2006Co-Authors: Nicole Anastos, Neil W. Barnett, Frederick M. Pfeffer, Simon W. LewisAbstract:This paper reports an investigation into the temporal stability of aqueous solutions of Psilocin and psilocybin reference drug standards over a period of fourteen days. This study was performed using high performance liquid chromatography utilising a (955% vlv) methanol: 10 mM ammonium formate, pH 3.5 mobile phase and absorption detection at 269 nm. It was found that the exclusion of light significantly prolonged the useful life of standards, with aqueous solutions of both Psilocin and psilocybin being stable over a period of seven days.
-
The determination of Psilocin and psilocybin in hallucinogenic mushrooms by HPLC utilizing a dual reagent acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II) chemiluminescence detection system.
Journal of forensic sciences, 2006Co-Authors: Nicole Anastos, Neil W. Barnett, Simon W. Lewis, D. Noel SimsAbstract:This paper describes a procedure for the determination of Psilocin and psilocybin in mushroom extracts using high-performance liquid chromatography with postcolumn chemiluminescence detection. A number of extraction methods for Psilocin and psilocybin in hallucinogenic mushrooms were investigated, with a simple methanolic extraction being found to be most effective. Psilocin and psilocybin were extracted from a variety of hallucinogenic mushrooms using methanol. The analytes were separated on a C12 column using a (95:5% v/v) methanol:10 mM ammonium formate, pH 3.5 mobile phase with a run time of 5 min. Detection was realized through a dual reagent chemiluminescence detection system of acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II). The chemiluminescence detection system gave improved detectability when compared with UV absorption at 269 nm, with detection limits of 1.2 x 10(-8) and 3.5 x 10(-9) mol/L being obtained for Psilocin and psilocybin, respectively. The procedure was applied to the determination of Psilocin and psilocybin in three Australian species of hallucinogenic mushroom.
-
Determination of Psilocin and psilocybin using flow injection analysis with acidic potassium permanganate and tris(2,2'-bipyridyl) ruthenium(II) chemiluminescence detection respectively
Talanta, 2005Co-Authors: Nicole Anastos, Neil W. Barnett, Simon W. Lewis, Nicholas Gathergood, Peter J. Scammells, D. Noel SimsAbstract:A simple, rapid and sensitive method for the determination of Psilocin and psilocybin is described. This is the first report on the determination of Psilocin and psilocybin using flow injection analysis with acidic potassium permanganate and tris(2,2′-bipyridyl)ruthenium(II) chemiluminescence. The limits of detection (signal-to-noise ratio = 3) are 9 × 10 −10 M and 3 × 10 −10 M for Psilocin and psilocybin, respectively.A concise synthetic route for Psilocin in three steps from readily available starting materials is also described. The structures were elucidated on the basis of spectroscopic data.
Simon W. Lewis - One of the best experts on this subject based on the ideXlab platform.
-
Investigation into the temporal stability of aqueous standard solutions of Psilocin and psilocybin using high performance liquid chromatography
Science & justice : journal of the Forensic Science Society, 2006Co-Authors: Nicole Anastos, Neil W. Barnett, Frederick M. Pfeffer, Simon W. LewisAbstract:This paper reports an investigation into the temporal stability of aqueous solutions of Psilocin and psilocybin reference drug standards over a period of fourteen days. This study was performed using high performance liquid chromatography utilising a (955% vlv) methanol: 10 mM ammonium formate, pH 3.5 mobile phase and absorption detection at 269 nm. It was found that the exclusion of light significantly prolonged the useful life of standards, with aqueous solutions of both Psilocin and psilocybin being stable over a period of seven days.
-
The determination of Psilocin and psilocybin in hallucinogenic mushrooms by HPLC utilizing a dual reagent acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II) chemiluminescence detection system.
Journal of forensic sciences, 2006Co-Authors: Nicole Anastos, Neil W. Barnett, Simon W. Lewis, D. Noel SimsAbstract:This paper describes a procedure for the determination of Psilocin and psilocybin in mushroom extracts using high-performance liquid chromatography with postcolumn chemiluminescence detection. A number of extraction methods for Psilocin and psilocybin in hallucinogenic mushrooms were investigated, with a simple methanolic extraction being found to be most effective. Psilocin and psilocybin were extracted from a variety of hallucinogenic mushrooms using methanol. The analytes were separated on a C12 column using a (95:5% v/v) methanol:10 mM ammonium formate, pH 3.5 mobile phase with a run time of 5 min. Detection was realized through a dual reagent chemiluminescence detection system of acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II). The chemiluminescence detection system gave improved detectability when compared with UV absorption at 269 nm, with detection limits of 1.2 x 10(-8) and 3.5 x 10(-9) mol/L being obtained for Psilocin and psilocybin, respectively. The procedure was applied to the determination of Psilocin and psilocybin in three Australian species of hallucinogenic mushroom.
-
Determination of Psilocin and psilocybin using flow injection analysis with acidic potassium permanganate and tris(2,2'-bipyridyl) ruthenium(II) chemiluminescence detection respectively
Talanta, 2005Co-Authors: Nicole Anastos, Neil W. Barnett, Simon W. Lewis, Nicholas Gathergood, Peter J. Scammells, D. Noel SimsAbstract:A simple, rapid and sensitive method for the determination of Psilocin and psilocybin is described. This is the first report on the determination of Psilocin and psilocybin using flow injection analysis with acidic potassium permanganate and tris(2,2′-bipyridyl)ruthenium(II) chemiluminescence. The limits of detection (signal-to-noise ratio = 3) are 9 × 10 −10 M and 3 × 10 −10 M for Psilocin and psilocybin, respectively.A concise synthetic route for Psilocin in three steps from readily available starting materials is also described. The structures were elucidated on the basis of spectroscopic data.
Elyes Dahmane - One of the best experts on this subject based on the ideXlab platform.
-
exposure response analysis to assess the concentration qtc relationship of psilocybin Psilocin
Clinical pharmacology in drug development, 2020Co-Authors: Elyes Dahmane, Paul R Hutson, Jogarao V S GobburuAbstract:Psilocybin is being developed for treating major depressive disorder. Psilocybin is readily dephosphorylated to Psilocin upon absorption. The potential for Psilocin proarrhythmic effect was assessed using a concentration-QTc interval (C-QTc) analysis from an open-label single ascending dose study of psilocybin. Psilocybin doses ranged from 0.3 to 0.6 mg/kg. This trial showed a significant but shallow C-QTc relationship. At the clinical dose of 25 mg, the mean Psilocin maximum concentration is 18.7 ng/mL, and the associated mean (upper 90% confidence interval of mean) QTcF change is 2.1 (6.6) milliseconds. Given the short half-life of Psilocin of about 4 hours, there would be no accumulation after monthly oral doses used in clinical trials. The upper limit of the 90% confidence interval of the model-predicted mean ΔQTcF crossed 10 milliseconds at a Psilocin concentration of 31.1 ng/mL. At a supraclinical Psilocin maximum concentration of about 60 ng/mL, ΔQTcF remains low, with a mean (upper limit of the 90% confidence interval) of 9.1 (17.9) milliseconds. This analysis enabled the characterization of the C-QTc relationship and prediction of QTc prolongation at the expected clinical and possible higher psilocybin doses.
-
Exposure‐Response Analysis to Assess the Concentration‐QTc Relationship of Psilocybin/Psilocin
Clinical pharmacology in drug development, 2020Co-Authors: Elyes Dahmane, Paul R Hutson, Jogarao V S GobburuAbstract:Psilocybin is being developed for treating major depressive disorder. Psilocybin is readily dephosphorylated to Psilocin upon absorption. The potential for Psilocin proarrhythmic effect was assessed using a concentration-QTc interval (C-QTc) analysis from an open-label single ascending dose study of psilocybin. Psilocybin doses ranged from 0.3 to 0.6 mg/kg. This trial showed a significant but shallow C-QTc relationship. At the clinical dose of 25 mg, the mean Psilocin maximum concentration is 18.7 ng/mL, and the associated mean (upper 90% confidence interval of mean) QTcF change is 2.1 (6.6) milliseconds. Given the short half-life of Psilocin of about 4 hours, there would be no accumulation after monthly oral doses used in clinical trials. The upper limit of the 90% confidence interval of the model-predicted mean ΔQTcF crossed 10 milliseconds at a Psilocin concentration of 31.1 ng/mL. At a supraclinical Psilocin maximum concentration of about 60 ng/mL, ΔQTcF remains low, with a mean (upper limit of the 90% confidence interval) of 9.1 (17.9) milliseconds. This analysis enabled the characterization of the C-QTc relationship and prediction of QTc prolongation at the expected clinical and possible higher psilocybin doses.
H. Köhler - One of the best experts on this subject based on the ideXlab platform.
-
Synthesis, hydrolysis and stability of Psilocin glucuronide.
Forensic science international, 2014Co-Authors: Rafaela Martin, Matthias Lehr, Jennifer Schürenkamp, Heidi Pfeiffer, H. KöhlerAbstract:A two-step synthesis of Psilocin glucuronide (PCG), the main metabolite of Psilocin, with methyl 2,3,4-tri-O-isobutyryl-1-O-trichloroacetimidoyl-α-d-glucopyranuronate is reported. With the synthesized PCG, hydrolysis conditions in serum and urine were optimized. Escherichia coli proved to be a better enzyme source for β-glucuronidase than Helix pomatia. It was essential to add ascorbic acid to serum samples to protect Psilocin during incubation. Furthermore the stability of PCG and Psilocin was compared as stability data are the basis for forensic interpretation of measurements. PCG showed a greater long-term stability after six months in deep frozen serum and urine samples than Psilocin. The short-term stability of PCG for one week in whole blood at room temperature and in deep frozen samples was also better than that of Psilocin. Therefore, PCG can be considered to be more stable than the labile Psilocin and should always be included if Psilocin is analyzed in samples.
-
a validated method for quantitation of Psilocin in plasma by lc ms ms and study of stability
International Journal of Legal Medicine, 2012Co-Authors: Rafaela Martin, Jennifer Schürenkamp, Heidi Pfeiffer, H. KöhlerAbstract:A liquid chromatography–electrospray ionization/tandem mass spectrometry method for the quantitation of Psilocin in plasma is presented. Sample workup was performed with mixed-mode solid-phase extraction using ascorbic acid and nitrogen for drying to protect the unstable analyte. Calibration curves were linear from 2 to 100 ng/mL, and no selectivity problems occurred. The limit of detection was 0.1 ng/mL, and the limit of quantitation was 0.34 ng/mL. Recovery was >86% and matrix effects were <110%. Both were reproducible. Interday and intraday precisions at different concentrations were 1.5–4.3% relative standard deviation, bias within ±9%. Processed samples were stable in the autosampler for at least 26 h. Furthermore, the stability of Psilocin in blood stored at different temperatures over various periods of time was investigated. Samples stored at room temperature showed a continuous decrease of analyte leading to a loss of about 90% after 1 week. Storage in the fridge improved sample stability significantly. Freezing of blood samples led to a not reproducible loss of Psilocin.
-
Development of a Psilocin immunoassay for serum and blood samples
International Journal of Legal Medicine, 2004Co-Authors: C. Albers, H. Köhler, M. Lehr, B. Brinkmann, J. BeikeAbstract:After the immunisation of rabbits with a Psilocin-specific immunogen, polyclonal antisera were obtained. With these antisera a competitive, heterogeneous radioimmunoassay for the detection of Psilocin was developed. As tracer a derivative of Psilocin was synthesised, which contained a tritiated CH_3 group. The antisera showed a specific reaction with Psilocin. The cross-reactivity of structurally related endogenous substances like serotonin, tryptophan and tyrosine was below 0.01%. Also common drugs of abuse (Δ^9-tetrahydrocannabinol, cocaine, morphine, amphetamine) showed negligible cross-reactivity (0.01–2%). Only tricyclic neuroleptics with a (dimethylamino)ethyl side-chain showed some cross-reactivity (20%). Spiked serum and blood samples were analysed with this new immunoassay and the results obtained were compared with the values measured with a validated GC-MS method.
-
Synthesis of a Psilocin hapten and a protein-hapten conjugate.
The Journal of pharmacy and pharmacology, 2002Co-Authors: Christian Albers, Matthias Lehr, J. Beike, H. Köhler, Bernd BrinkmannAbstract:Derivatives of Psilocin with omega-functionalized alkyl spacers in position 1 of the indole ring were synthesized as haptens for use in a radioimmunoassay. Whereas the Psilocin analogues with a 3-aminopropyl and a 4-aminobutyl moiety at the indole nitrogen decomposed during synthesis, the analogous 3-carboxypropyl Psilocin derivative proved to be stable. This compound was coupled to bovine serum albumin (BSA) using the N-hydroxysuccinimide ester-mediated conjugation. The protein-hapten conjugate was characterized by matrix-assisted laser desorption ionization mass spectrometry. The mass spectrometry data indicated an average incorporation ratio of 4-5 molecules of Psilocin hapten per molecule of BSA.
