A Tryptamine Comeback: Interest Beyond Illicit Use

By: Maximilian Magana, Cerilliant/Sigma-Aldrich; Derrell Johnson, Cerilliant/Sigma-Aldrich, Analytix Volume 3, 2015

Solution Certified Reference Materials of Tryptamines

Natural and synthetic tryptamines are used recreationally for their hallucinogenic and stimulant properties. In recent years, synthetic tryptamine analogs have experienced a resurgence of abuse. The main drivers for this resurgence include their ease of availability on clandestine and legal websites combined with a growing trend among drug users to vaporize tryptamines using e-cigarette devices1,2.

Substituted tryptamine analogs including 5-MeO-DALT, 4-OH-DiPT and 4-AcO-DMT can offer increased potencies compared to natural tryptamines as a result of functional group modification3. These novel psychoactive substances (NPS) can be synthesized from naturally-occurring tryptamines, such as N,N-dimethyltryptamine (DMT) or psilocin, by introducing a methoxy, hydroxy or acetoxy group at the four or five position of the indole ring. Tryptamines with substitution at the five position typically possess more hallucinogenic potency than their unsubstituted counterparts or analogs with indole ring substitutions at the six or seven positions3. 5-MeO-DiPT, for example, is seven times more potent than DMT3.

In addition to increasing hallucinogenic potency for illicit use, structural modification of natural tryptamines also provides opportunities in pharmaceutical drug development of new therapeutics. Tryptamines have emerged as drug candidates for managing treatment of anxiety, clinical depression, cluster headaches and substance abuse disorders3. Other potential pharmaceutical applications of tryptamines include as tools in identifying targets for new antipsychotic drugs3.

Pharmacological studies investigating the neurochemical pathway of tryptamines have shown different levels of agonistic activity upon varying the functional group at the five position of the indole ring4. These types of studies are essential to tryptamine drug development, allowing researchers to better understand the therapeutic efficacy of natural tryptamines – like psilocybin and DMT – and their synthetic analogs in treating disease4.

Mass spectrometry-based techniques are used for the screening and confirmatory analysis of tryptamine analogs in applications ranging from clinical toxicology and forensic analysis to pharmaceutical research. Natural and synthetic tryptamines are sufficiently volatile for analysis by GC/MS5. While five-substituted tryptamine analogs do not require derivatization prior to GC/MS analysis, derivatization is necessary for naturally-occurring tryptamines like psilocybin, for example, to prevent on-column degradation to psilocin5,6. Although five-substituted tryptamines are amenable to GC/ MS analysis without derivatization, some studies report that adding a trimethylsilyl derivatizing agent can improve peak shape and intensities6.

Testing laboratories have begun to adopt LC-MS and LC-MS/MS analytical methods for analysis of tryptamine analogs. These methods permit characterization of thermally unstable tryptamines without derivatization as well as the direct, simultaneous analysis of tryptamines and other NPS in a single run6. Screening and confirmation of tryptamines in clinical toxicology applications are expected to increase in coming years as abuse of this illicit drug class widens and as the acquisition and ownership costs of LC-MS/MS decreases7.

Studies have shown that light and air can rapidly degrade aqueous solutions of tryptamines, resulting in poor accuracy of the reference solution8. Cerilliant’s validated process includes manufacturing controls for sensitive compounds such as raw material handling and solution preparation under inert conditions and flame-sealing under argon in amber ampoules to minimize degradation from light and air and to promote long-term shelf life. From synthesis design to performing accelerated and real-time stability studies, Cerilliant’s certified reference standards are designed to ensure accuracy and reliability of results and to support laboratory regulatory requirements.

Visit sigma-aldrich.com/cerilliant to view Cerilliant’s catalog offering of certified solution standards of naturally-occurring and synthetic tryptamines that are packaged in a US DEA and Health Canada (with TK #s)-exempt solution format.

To receive news on the latest reference standards introduced by Cerilliant, register at sigma-aldrich.com/registercerilliant.

 

Cerilliant Certified Spiking Solutions® of Tryptamines

Cat. No. Description Package Size
B-022 Bufotenine 1.0 mg/mL in Acetonitrile
D-102 N,N-Dimethyltryptamine (DMT) 1.0 mg/mL in Methanol
M-095 Melatonin 1.0 mg/mL in Methanol
M-165 5-MeO-DALT 1.0 mg/mL in Acetonitrile
M-166 5-MeO-MiPT HCl 1.0 mg/mL (as free base) in Methanol
M-167 5-MeO-DiPT HCl 1.0 mg/mL in methanol
M-168 5-MeO-DMT 1.0 mg/mL in Methanol
M-169 5-MeO-AMT 1.0 mg/mL in methanol
P-048 Psilocin 5 mg
P-049 Psilocin-D10 5 mg
P-098 Psilocin 1.0 mg/mL in Acetonitrile
P-099 Psilocin-D10 100 µg/mL in Acetonitrile
P-097 Psilocybin 1.0 mg/mL in 1:1 Acetonitrile:Water
P-113 Psilocybin-D4 100 µg/mL in 1:1 Acetonitrile:Water

 

 References

  1. Accessed 04 March 2015 from http://informahealthcare.com/doi/abs/10.310 9/15563650.2014.885983
  2. Accessed 04 March 2015 from http://www.nflfl.com/e- cigarettes-adapted-smoke-illegal-drugs/#.VP8LNPzF86t
  3. Dargan, P.; Wood, D. Novel Psychoactive Substances: Classification, Pharmacology and Toxicology. First Edition. Academic Press. 2013.
  4. Accessed 04 March 2015 from http://www.ncbi.nlm.nih.gov/pubmed/24800892
  5. Accessed 04 March 2015 from http://www.sciencedirect.com/science/article/pii/S0165993610001433
  6. Accessed 04 March 2015 from http://link.springer.com/article/10.1007%2Fs11419-009-0087-9
  7. Accessed 04 March 2015 from http://scitechnol.com/the-use-of-syntheticcathinones-and-tryptamines-in-a-psychiatric-population-ImWc.php?article_id=1378
  8. Accessed 04 March 2015 from http://www.ncbi.nlm.nih.gov/pubmed/17002211