The search for stimulant alkaloids: from MS sources to sources of highs

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  • Published: Mar 1, 2017
  • Author: Ryan De Vooght-Johnson
  • Channels: Gas Chromatography
thumbnail image: The search for stimulant alkaloids: from MS sources to sources of highs

Are the qat tree’s stimulant alkaloids found in other plants?

The qat plant is a shrub or small tree, widely grown in Yemen and the Horn of Africa for its leaves, which are chewed as a stimulant. Qat is classed as an illegal drug in the UK and many other EU countries, although it is legal in Yemen and most East African countries. Qat leaves contain three stimulant alkaloids: cathinone, (2S)-2-amino-1-phenyl-1-propanone; cathine, (1S,2S)-2-amino-1-phenyl-1-propanol; and (1R,2S)-norephedrine, (1R,2S)-2-amino-1-phenyl-1-propanol. Cathinone is believed to be the most active compound, but it degrades as the harvested leaves age. The active compounds are structurally related to amphetamines, having similar, but somewhat milder, effects. To date, these stimulant alkaloids have only been found in the qat tree, Catha edulis, and a couple of totally unrelated plants of the Ephedra genus. The Colorado researchers thought it possible that some plants related to the qat tree might also contain some of the active alkaloids. They therefore obtained leaf samples from 43 related plants, two which had supposed stimulant properties, in order to examine them for the active alkaloids using GC/MS for identification. However, the use of GC required derivatisation, since these polar alkaloids are not volatile enough to readily undergo GC in their native state.

Double-derivatisation GC method

The Colorado researchers examined ways to derivatise the three active alkaloids. Many derivatisation methods for amphetamines and related substances tend to give multiple derivatives. It was found that good results were obtained with a two-step method: the derivatives were first treated with a mixture of N-methyl-N-(trimethylsilyl)-trifluoroacetamide (MSTFA) and trimethylsilylimidazole (this combination silylates OH groups, but not primary amines), then with N-methyl-bistrifluoroacetamide (which gives trifluoroacetamides with primary amine groups). In this way, single derivatives were formed, not multiple mixtures.

Using a purchased cathine standard, which was successfully derivatised, a GC/MS method was devised. A Thermo 30m TG-5MS column was used, with a temperature gradient running from 80 to 310 °C. The mass spectrometer was a Thermo DSQ II model, used with an electron ionisation source in positive mode. The linearity was found to be good, while the limit of detection (LOD) for cathine was 0.2 μg/ml and the limit of quantification (LOQ) 0.8 μg/ml, equating to an LOD of 0.03 μg/100 mg of dried leaf and an LOQ of 0.1 μg/100 mg of dried leaf. It was not possible to purchase cathinone as a standard, owing to Drug Enforcement Administration restrictions.

Ground leaf samples from the various species were extracted with water, and caffeine was added as an internal standard. The aqueous extracts were basified with sodium hydroxide (converting alkaloid salts, etc. to the free bases), and then extracted with t-butyl methyl ether, which was then evaporated under a stream of nitrogen. Derivatisation was carried out as detailed above on the evaporated extracts. It was found that only the qat leaf extracts contained cathine, while cathinone was not noted in any samples (presumably it was not in the qat samples since the leaves were not fresh enough). A non-stimulant alkaloid, 2-phenylethylamine, was noted in five of the species examined, but not in the qat leaves.

Although the search for stimulant alkaloids was negative, a large number of other compounds were identified, including terpenoids and sterols, some of which may be novel. Principal component analysis (PCA) was used to classify the large range of compounds found.

Search for stimulant alkaloids unsuccessful

The extraction and derivatisation methods used seem to have worked well. However, despite looking at a large number of species, no stimulant alkaloids were found, apart from those from qat leaves. Doubtless the search for new sources of stimulants will continue, although whether a successful discovery would bring benefits that outweigh the possible harm is open to question.

Related Links

Phytochemical Analysis, 2017, Early View paper. Tembrock et al. Employing two-stage derivatisation and GC–MS to assay for cathine and related stimulant alkaloids across the Celastraceae.

Wikipedia, Khat

Article by Ryan De Vooght-Johnson

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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