CHROMATOGRAPHY-MASS SPECTROMETRY ANALYSIS OF TIANEPTINE IN URINE

  • N. V. Horlachuk I. HORBACHEVSKY TERNOPIL STATE MEDICAL UNIVERSITY
  • L. M. Mosula I. HORBACHEVSKY TERNOPIL STATE MEDICAL UNIVERSITY
  • N. O. Zarivna I. HORBACHEVSKY TERNOPIL STATE MEDICAL UNIVERSITY
Keywords: tianeptine, metabolites, chromatography-mass spectrometry, extracts, antidepressants

Abstract

Introduction. Coaxil (tianeptine) is a new generation antidepressant with selective serotoninergic action. Recently, a significant increase in non-medical use of the atypical tricyclic antidepressant drug, tianeptine, has been observed in Ukraine. According to domestic narcologists and psychiatrists there is information on tianeptine abuse by drug addicts. In the literature there is information that this medicine combines characteristics of opium, heroin and cocaine in it. Receiving of tianeptine in high dosages (400-600 mg intravenously) leads to a state of euphoria and gives a narcotic effect that is several times stronger than heroin and cocaine.

The aim of the study – to learn and define tianeptine metabolites in the human body, which are detected in urine, in the course of research by gas chromatography and gas chromatography-mass spectrometry.

Research Methods. The analysis has been carried out on a gas chromatograph Agilent 6890N with a mass-selective detector Agilent 5973 and an injector Agilent 7683 (USA) equipped with a chromatographic quartz capillary geyser of FactorFOUR Varian (USA). Gas carrier - helium.

Results and Discussion. The analysis of extracts received as with acidic and with alkaline pH values, has shown metabolites of tianeptine MC5 in them. Besides the main metabolite (MC5), there have also been dezalkyldezaminotianeptine and dezalkyldezaminonortianeptine in the extracts obtained at pH 3-4, and in the extracts obtained at pH 9-10 - dezalkyltianeptine and a metabolite, the structure of which has not been established at the moment. Based on the fact that the main metabolite of tianeptine MC5 is isolated from the urine both at acidic pH values ​​(pH = 3-4) and at alkaline (pH = 9-10), it is possible to use as acidic as alkaline extracts for the chromatography-mass spectrometry analysis.

Conclusions. The possibility of using gas chromatography and mass spectrometry methods for metabolites has been shown. The main metabolite of tianeptine can be isolated from the urine at acidic, and also at alkaline pH values of the medium.

References

Ranevskiy, K.S. (2010). Antidepressanty: teyrokhimicheskiye aspekty mekhanizma deystviya [Antidepressants, in addition to being effective therapeutic agents for depression, have also proved to be multifaceted drugs useful for treating a number of other psychiatric and neurologic disorders]. Psykhiatriya i psikhofarmakoterapiya – Psychiatry and Psychopharmacotherapy, 1, (3), 35-38 [in Russian].

Caccia, S. (2009). Metabolism of the newer antidepressants. Clin. Pharmacokinet., 34, (4), 292-294.

Labrid, C., Labrid, C., Mocaer, E., & Kamoun, A. (2009). Neurochemical and pharmacological properties of tianeptine, a novel anti-depressant. Br. J. Psychiatry,160, 56-60.

Fromenty, B., Fromenty,B., Freneaux, E., & Lable, Q. (2009). Tianeptine, a new tricyclie antidepressant metabolized by beta − oxidation of its heptanoic side chain, inhibits the mitochondrial oxidation of medium and short chain fatty acids in mice. Biochem. Pharmacol., 1, (21), 43-51.

Leterme , L., Singlan,Y., & Auclair V. (2008). Misuse of tianeptine: five cases of abuse. Ann. Med. In., 2, 58-63.

Ryabtseva, A., & Bardeeva, Yu. (2013). Toksicheskoye porazheniya organa zreniya u inyektsionykh potrebiteley tianeptina [Tianeptine is an atypical antidepressant with a unique mechanism of action and recently it has been also reported that its major metabolite, compound MC5, possesses pharmacological activity similar to that of the parent drug]. Narkologiya – Narcology, 1, 25-28 [in Russian].

Gaulier, J.M., Marquet, P., Lacassie, E. (2012). High-performance liquid chromatographic determination of tianeptine in plasma applied to pharmacokinetic studies. J. Chromatogr. B., 748, 407-414.

Caсcia, S. (2008). Metabolism of the newer antidepressants. An overview of the pharmacological and pharmacokinetiс implications. Clin. Pharmacokinet., 34, (4), 281-302.

Santana, F., Bonato, P. (2008).Enantioselective analysis of mianserin and its two major metabolites in human plasma by liquid chromatography – mass spectrometry after three phase liquid phase microextraction. Anal. Chim. 606, (1), 80–91.

Published
2019-02-06
How to Cite
Horlachuk, N., Mosula, L., & Zarivna, N. (2019). CHROMATOGRAPHY-MASS SPECTROMETRY ANALYSIS OF TIANEPTINE IN URINE. Medical and Clinical Chemistry, (4), 146-152. https://doi.org/10.11603/mcch.2410-681X.2018.v0.i4.9828
Section
ORIGINAL INVESTIGATIONS