Development of a LC–MS/MS Method to Analyze 5-Methoxy-N,N-Dimethyltryptamine and Bufotenine: Application to Pharmacokinetic Study
Hong-Wu Shen, Xi-Ling Jiang, Ai-Ming Yu
Bioanalysis March 27, 2009 DOI: 10.4155/bio.09.7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Method development and validation with pharmacokinetic analysis Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | 5-MeO-DMT |
| Dose | 2 mg/kg |
| Topics | 5-MeO-DMT DMT |
| Keywords | Chromatography Metabolite Protein precipitation Pharmacokinetics Pharmacology |
| Citations | 26 |
| Key points | The systemic exposure to the active metabolite bufotenine was about 1/14 that of 5-MeO-DMT, and because bufotenine has roughly tenfold higher affinity for the 5-HT2A receptor, it may significantly contribute to the pharmacological and toxicological effects of 5-MeO-DMT. |
Abstract
Introduction: 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a psychoactive indolealkylamine substance that has been used for recreational purpose and may lead to fatal toxicity. While 5-MeO-DMT is mainly inactivated via deamination, it is O-demethylated to an active metabolite, bufotenine. Quantitation of 5-MeO-DMT and bufotenine is essential to understand the exposure to and the effects of drug and metabolite. This study, therefore, aimed to develop and validate a LC-MS/MS method for simultaneous analysis of 5-MeO-DMT and bufotenine in mouse serum.
Methods: A simple protein precipitation method coupled with an optimal gradient elution was used for sample preparation and separation. Detection of 5-MeO-DMT and bufotenine was accomplished using multiple reaction monitoring of m/z 219.2→174.2 and 205.2→160.2, respectively, in the positive ion mode. 5-Methyl-N,N-dimethyltrypamine (m/z 203.2→158.3) was used as internal standard for quantification. Accuracy and precision were determined after the analyses of quality control samples. Validated assay was then employed to determine drug and metabolite concentrations in serum samples collected from mice at different time points after intraperitoneal administration of 5-MeO-DMT (2 mg/kg).
Results: With a total run time of 9 min, 5-MeO-DMT and bufotenine were eluted at 2.8 and 5.6 min, respectively. The assay was linear over the range 0.90-5,890 ng/mL (1.12-7,360 pg on-column) for 5-MeO-DMT and 2.52-5,510 ng/mL (3.14-6,890 pg) for bufotenine. Intra- and inter-day precision and accuracy were within 15% for both analytes. The recovery of each analyte from 20 µL of serum containing 8.08, 72.7 and 655 ng/mL of 5-MeO-DMT and 7.56, 68.1 and 613 ng/mL of bufotenine was more than 75%. Pharmacokinetic analysis revealed that the systemic exposure (area under the curve) to metabolite bufotenine was about 1/14 of that to 5-MeO-DMT.
Conclusion: This LC-MS/MS method is a sensitive and reliable assay for quantitation of blood 5-MeO-DMT and bufotenine. Given the fact that bufotenine acts on 5-HT(2A) receptor with an affinity about 10-fold higher than 5-MeO-DMT, the active metabolite bufotenine may significantly contribute to the apparent pharmacological and toxicological effects of 5-MeO-DMT.
Comparable studies
Other preclinical and animal studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Mice and rats | 2006 | Preclinical study | |
| Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Rats and transfected fibroblasts | 1998 | Experimental study | |
| Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat Intact rats and rats depleted of monoamines with reserpine | 1985 | Experimental study |
Citations in the library
Cited by 13
- Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Current Drug Metabolism October 1, 2010
- A narrative synthesis of research with 5-MeO-DMT. Journal of Psychopharmacology March 1, 2022
- Effects of monoamine oxidase inhibitor and cytochrome P450 2D6 status on 5-methoxy-N,N-dimethyltryptamine metabolism and pharmacokinetics. Biochemical Pharmacology July 1, 2010
- Pharmacokinetic interactions between monoamine oxidase A inhibitor harmaline and 5-methoxy-N,N-dimethyltryptamine, and the impact of CYP2D6 status. Drug Metabolism and Disposition May 1, 2013
- Nonlinear pharmacokinetics of 5-methoxy-N,N-dimethyltryptamine in mice. Drug Metabolism and Disposition July 1, 2011
and 8 more in the library
Cites 16
- Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges. Pharmacology & Therapeutics May 1, 2004
- A fatal intoxication following the ingestion of 5-methoxy-N,N-dimethyltryptamine in an ayahuasca preparation. Journal of Analytical Toxicology 2005
- Monoamine oxidase inhibitor poisoning resulting from Internet misinformation on illicit substances. Journal of Toxicology Clinical Toxicology 2004
- Rhabdomyolysis after ingestion of "foxy," a hallucinogenic tryptamine derivative. Mayo Clinic Proceedings April 1, 2006
- Pharmepéna-Psychonautics: Human intranasal, sublingual and oral pharmacology of 5-methoxy-N,N-dimethyl-tryptamine. Journal of Psychoactive Drugs 2001
and 11 more in the library