Determination of pharmacological levels of harmane, harmine and harmaline in mammalian brain tissue, cerebrospinal fluid and plasma by high-performance liquid chromatography with fluorimetric detection

Moncrieff, Joan

doi:10.1016/s0378-4347(00)82576-1

Cited by 41 publications

(17 citation statements)

References 16 publications

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“…Harmane is very lipid soluble (Zetler et al, 1972), and broadly distributed within the rat brain (Anderson et al, 2006;Matsubara et al, 1993;Moncrieff, 1989). Brain concentrations are several fold higher than those in the blood in both exposed (i.e., harmane-injected) laboratory animals and in control animals (Anderson et al, 2006;Zetler et al, 1972).…”

Section: Introductionmentioning

confidence: 99%

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Louis

2008

NeuroToxicology

127

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Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors likely play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. In 2002, we demonstrated elevated blood harmane concentrations in an initial sample of 100 ET cases compared to 100 controls. Between 2002 and 2007, we assembled a new and larger sample of ET cases and controls. We now attempt to replicate our previous findings. Cases and controls were frequency-matched on age, gender, and race. Blood harmane concentrations were quantified by high performance liquid chromatography. Subjects comprised 150 ET cases and 135 controls (mean age 65.3 ± 15.5 vs. 65.5 ± 14.2 years, p = 0.94). Mean log blood harmane concentration was ∼50% higher in cases than controls (0.50 ± 0.54 g -10 /ml vs. 0.35 ± 0.62 g -10 /ml, p = 0.038). In a logistic regression analysis, log blood harmane concentration was associated with ET (OR adjusted 1.56, 95% CI 1.01 -2.42, p = 0.04), and odds of ET was 1.90 (95% CI 1.07 -3.39, p = 0.029) in the highest vs. lowest log blood harmane tertile. Log blood harmane was highest in ET cases with familial ET (0.53 ± 0.57 g -10 /ml), intermediate in cases with sporadic ET (0.43 ± 0.45 g -10 /ml) and lowest in controls (0.35 ± 0.62 g -10 /ml) (test for trend, p = 0.026). Blood harmane appears to be elevated in ET. The higher concentrations in familial ET suggests that the mechanism may involve genetic factors.

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Section: Introductionmentioning

confidence: 99%

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Louis

2008

NeuroToxicology

127

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“…Moncrieff described an HPLC method to quantitate harmane, harmine, and harmaline in CSF and plasma without sample extraction (4). No data from humans were presented.…”

Section: Resultsmentioning

confidence: 99%

Determination of Harmane and Harmine in Human Blood Using Reversed-Phased High-Performance Liquid Chromatography and Fluorescence Detection

Zheng

Wang

Barnes

et al. 2000

Analytical Biochemistry

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A number of tremorogenic β-carboline alkaloids have been found in common plant-derived foodstuffs, beverages, and inhaled substances. Because of their natural presence in the food chain, there is a growing concern regarding the potential risks of certain essen tial tremors associated with the long-term low-level dietary exposure to these alkaloids. The purpose of this study was to develop an effective analytical method to determine blood levels of two major β-car boline derivatives, harmane and harmine. Human blood was extracted with ethyl acetate and methyl-tbutyl ether (2:98) under an alkaline condition. After evaporation of organic solvent, the samples were re-constructed in methanol. The samples were fraction ated on a 250 × 4.6-mm C18 reversed-phase column with an isocratic mobile system consisting of 17.5 mM potassium phosphate buffer (ph 6.5) and methanol (30: 70), followed by an on-line fluorescence detection. The method had the detection limit to determine 206 and 81 pg/ml of harmane and harmine, respectively, in 10 ml of human blood. The intraday precision (C.V.) at 25 ng/ml was less than 6.7 and 3.4% for harmane and harmine, respectively. The interday precision was 7.3% for harmane and 5.4% for harmine. The method has proven sensitive, reproducible, and thus useful for both laboratory and clinical studies of β-carboline toxicities.A number of tremorogenic β-carboline alkaloids such as harmane, harmine, harmaline, and ibogaine have been found in common plant-derived foodstuffs (wheat, rice, corn, barley, soybeans, rye, grapes, mushrooms, vinegar). plant -derived beverages (wine. beer. whisky. brandy, sake). and plant-derived inhaled substances (tobacco) (1, 6). These substances are also endogenous to animal tissue (6, 9) and have been isolated in beef and sardines (1). Laboratory animals exposed to these chemicals result in an acute action tremor (5). Because of their natural presence in the food chain, it is conceivable that the route of exposure in humans would be from dietary sources, smoking. and consumption of alcoholic beverages. In fact, the occurrence of β-carbo-lines in human blood under normal physiological Copyright © 2000 by Academic Press All rights of reproduction in any form reserved. Rommelspacher et al. employed thin-layer gel-plate separation and mul tiple extraction followed by high-performance liquid chromatography (HPLC) to detect 6-0H-tetrahydronorharmane (6-0H-THN) in rat and human sam ples (9). The substantial precolumn preparation in that study limited its application to clinical monitoring of this and other β-carbolines. Moncrieff also reported an HPLC method for tissue harmane, harmine, and harmaline (4). However, the quantitation of three compounds required three different mobile phases and three separate HPLC runs. A better HPLC method was developed by Adachi et al.(1) for determination norharmane and harmane in foodstuffs. Nevertheless, the adaptability of this method to biological remains uncertain. Moreover, to the best of our knowledge, there has been no report ...

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“…These techniques particularly include modern separation methods such as capillary electrophoresis [9], high-performance liquid chromatography (HPLC) with electrochemical detection [10,11] and with different types of spectral detection such as UV [12], FTIR [13], NMR [14], chemiluminescence [15], fluorescence [16] and mass spectrometry [17] as well as gas chromatography with a nitrogen-phosphorus detector [18,19] and mass spectrometry [20]. Most of above mentioned methods offer very useful analytical information about HME in terms of identification and quantification, excellent resolution, sensitivity and selectivity, however they require highly sophisticated and expensive instrumentation and often involve long analysis time and time-consuming sample pretreatment processes (derivatization, purification, complex extraction steps).…”

Section: Introductionmentioning

confidence: 99%

Voltammetric determination of harmaline in natural food products using boron-doped diamond electrode

Švorc

Cinková

Samphao

et al. 2015

Journal of Electroanalytical Chemistry

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Determination of pharmacological levels of harmane, harmine and harmaline in mammalian brain tissue, cerebrospinal fluid and plasma by high-performance liquid chromatography with fluorimetric detection

Cited by 41 publications

References 16 publications

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Determination of Harmane and Harmine in Human Blood Using Reversed-Phased High-Performance Liquid Chromatography and Fluorescence Detection

Voltammetric determination of harmaline in natural food products using boron-doped diamond electrode

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