Optimization of detection range of hydrazides of carboxylic acids and 2-acylhydrazinсarbothioamids by HPLC-ECI-MC

  • B. О. Varynskyi Zaporizhzhia State Medical University
Keywords: high performance liquid chromatography, mass spectrometric detection, electrospray ionization, hydrazides, сarbothioamids, optimization


Elaboration of control steps of hydrazids and сarbothioamids, raw materials  in the synthesis of 1,2,4-triazol-3-yl-thioacetate acids, potential drug substances on research and production stage is an important task. The study of adsorption, distribution, metabolism and excretion of these substances has great importance. The HPLC-MS is the most universal and selective method used in these cases.

The aim of our study was to determine the optimal conditions for mass spectrometric detection of ionization in electrospray in HPLC-MS іzonіcotinohydrazide, furan-2-carbohydrazide, 2-morpholinoacetohydrazide, 2-methoxybenzohydrazide, 2-isonicotinoyl-N-(2-methoxyphenyl)hydrazine-1-carbothioamide, 2-(furan-2-carbonyl)-N-phenylhydrazine-1-carbothioamide, 2-(2-morpholinoacetyl)-N-phenylhydrazine-1-carbothioamide, N-methyl-2-(2-morpholinoacetyl)hydrazine-1-carbothioamide, 2-(2-methoxybenzoyl)hydrazine-1-carbothioamide, precursor substances in the synthesis of salts of 1,2,4-triazol-3-yl-thioacetate acids for 8 synthetic schemes using full factorial design on 3 factors and polynomial regression equations.

Work was carried out using flow injection analysis (the technique of direct sample introduction into the ion source) on a liquid chromatograph Agilent 1260 Infinity HPLC System with a single quadrupole mass spectrometer Agilent 6120.

The optimal conditions of mass spectrometric detection series hydrazides and сarbothioamides for HPLC-ESI-MS on the basis of the calculated maxima polynomial regression functions were obtained. The equation of polynomial regression for the corresponding hydrazides and carbatioamides were suggested. The equations show the dependence of the mass detector signal intensity on three important factors: dryng gas temperature, the fragmentor voltage, the nebulizer pressure. The optimal conditions of mass spectrometric detection choice to maximize the signal detector and thus increase the sensitivity and selectivity of the determinations. It may allow partially separate the signal of these substances from the impurities signal because these conditions have specificity.


1. Jovic Z., Zivanovic L., Radisic M. et al. Schemometrically Assisted Development and Validation of LC-UV and LC-MS Methods for Simultaneous Determination of Torasemides and Its Impurities // J. Chromatogr. Sci - 2012. - V.50. - P. 324-334.

2. Malli L. M., Sarkahian A. B., Kulishoff J. M. et al. Open-access liquid chromatography-mass spectrometry in a drug discovery environment // J. Mass Spectrom. - 2002. - V. 37. - P. 889-896.

3. Benayad Z., Gómez-Cordovés C., Es-Safi N. E. Characterization of Flavonoid Glycosides from Fenugreek (Trigonella foenum-graecum) Crude Seeds by HPLC-DAD-ESI / MS Analysis // Int. J. Mol. Sci - 2014. -V 15. - P. 20668-20685.

4. Duan H.-F., Ding L., Li X.-B. et al Determination of cefcapene acid by LC-MS and their application to a pharmacokinetic study in healthy Chinese volunteers // J. Pharm. Sci - 2013. - V. 3, N 2. - P. 84-92.

5. Li L., Ma P., Wei J. et al. LC-ESI-MS method for the determination of dexamethasone acetate in the skin of a nude mouse // J. Chromatogr. B. - 2013. - V. 933. - P. 44-49.

6. Kaplushenko A.G., Panasenko O.I., Knysh E.G. and others. Synthesis, physicochemical and biological properties of 2- (5-R1-4-R2-1,2,4-triazole-3-thio) acetate acids // Pharmac. journ - 2008. - No. 2. - C. 67-72.

7. Kaploushenko AG Synthesis, structure and biological activity of derivatives of 4-mono- and 4,5-disubstituted 1,2,4-triazole-3-thione: Author's abstract. dis ... Dr. farm. Sciences: 15.00.02. / Zaporozhye state honey. Un-tete, 2012. - 43 p.

8. Shcherbina R. O., Panasenko O. I., Knysh E. G. and others. Synthesis and Physicochemical Properties of 2 - ((4-R-3- (morpholinomethylene) -4H-1,2,4-triazol-5-yl) thio) acetate acids // Actual questions of the pharmaceutical. and honey science and practice. - 2014. - No. 3. - P. 18-21.

9. Samelyuk Yu.G., Kaplaushenko A.G. Synthesis, physicochemical and biological properties of 2- (5- (methoxyphenyl) -1,2,4-triazole-3-thio) acetate acids and their esters // There itself. - 2013. - № 2. - P. 125-128.
How to Cite
VarynskyiB. О. (2018). Optimization of detection range of hydrazides of carboxylic acids and 2-acylhydrazinсarbothioamids by HPLC-ECI-MC. Farmatsevtychnyi Zhurnal, (4), 59-64. https://doi.org/10.32352/0367-3057.4.15.02
Synthesis and analysis of biologically active compounds