The study of retention regularities for the potential drug substances of 1,2,4-triazol-3-ylthioacetic acids and their salts series by the method of HPLC/DAD-MS

B. O. Varynskyi, Ye. G. Knysh, V. V. Parchenko, A. G. Kaplaushenko

Abstract


The derivatives of 1,2,4-triazole are potential drug substances with various biological activity. The control of stages for obtaining such compounds at the research and production phase is an important task of modern pharmaceutical science. HPLC/DAD-MS is the most universal and selective method, which allows to confirm the structure both of active substances and impurities and determine the content of analytes. The aim of the research is to study the dependence of the retention characteristic for the series of 1,2,4-triazol-3-ylthioacetic acids and their salts, which are the target products in the synthesis of the registered and potential drug substances by 8 synthetic schemes, on the content of acetonitrile in the mobile phase under the conditions of HPLC/DAD-MS determination. The dependence of the capacity factor k on the content of acetonitrile for 1,2,4-triazol-3-ylthioacetic acids and their salts has been determined. The possibilities of choice of conditions for determining these compounds both individually and in mixtures have been shown. It has been found that the reversed-phase retention mechanism for 1,2,4-triazol-3-ylthioacetic acids under study up to 65% content of acetonitrile in the eluent, and then the ion-exchange mechanism of interaction with silanol groups are observed. The exponential character of correlation between logD and capacity factors for the compounds tested has been determined for 15% content of acetonitrile in the mobile phase. It has been determined that correlation between logD and decimal logarithms of capacity factors for the compounds to be investigated has the linear character for 15% content of acetonitrile in the mobile phase.


Keywords


retention characteristics; 1,2,4-triazol-3-ylthioacetic acids; HPLC/DMD-MS

References


Shatts V. D., Sahartova O. V. Vyisokoeffektivnaya zhidkostnaya hromatografiya: Osnovyi teorii. Metodologiya. Primenenie v lekarstvennoy himii – Highperformance liquid chromatography: Theory foundations. Methodology. Application in medicinal chemistry, Riga: Zinatne, 1988, 390 p.

Podunavac-Kuzmanović S. O., Jevrić L. R., Tepić A. N., Šumić Z. Hem. Ind., 2013, No.67(6), pp.933-940.

Nasal A., Kaliszan R. Curr. Comp.-Aided Drug Design, 2006, No.2, pp.327-340.

Henchoz Y., Guillarme D., Martel S. et al. Anal. Bioanal. Chem., 2009, No.394 (7), pp.1919-1930.

Guillot A., Henchoz Y., Moccand C. et al. Chem. Biodiversity, 2009, No.6(11), pp.1828-1836.

Perisic-Janjic N., Kaliszan R., Wiczling P. Mol. Pharm., 2011, No.2, pp.555-563.

Wiczling P., Struck-Lewicka W., Kubik Ł. et al. Anal. Chem., 2006, No.78(1), pp.239-249.

Zheng B., West L. M. J. Liq. Chromatogr. Relat. Technol., 2009, No.33(1), pp.118-132.

Lombardo F., Shalaeva M. Y., Tupper K. A. et al. J. Med. Chem., 2000, No.43, pp.2922-2928.

Hawrył A., Kuśmierz E., Hawrył M., et al. J. Liq. Chrom. R. T., 2015, No.38, pp.430-437.

Lombardo F., Shalaeva Marina Y., Tupper Karl A. et al. J. Med. Chem., 2001, No.44, pp.2490-2497.

Snyder L. R., Dolan J. W. High-Performance Gradient Elution: The Practical Application of the Linear-Solvent-Strength Model, New Jersey: John Wiley & Sons, Inc., 2007, 461 p.

Xia L., Yong L., Juan Ch., Yan-Ping Sh. J. Chrom. Sci., 2010, No.48, pp.76-80.

Baeza-Baeza J. J., Ortiz-Bolsico C., Torres-Lapasió J. R., García-Álvarez-Coque M. C. J. Chrom. A., 2013, No.1284, pp.28-35.

Hong Y. L., Ding Y., Wang L. et al. J. Liq. Chrom R. T., 1999, No.22(6), pp.897-907.

Varynskyi B. O. Odeskyi medychnyi zhurnal – Odessa medical journal, 2015, No.4, pp.17-21.

Georgievskiy G. V., Kulikov A. Yu. Farmakom, 2009, No.2, pp.67-98.

Georgievskiy G. V. Analitychne zabezpechennia syntezu, standartyzatsii ta orhanizatsii vyrobnytstva pokhidnykh 1,2,4-tryazolu ta yikh likarskykh form – Analytical software for the synthesis, standardization and organization of manufacturing of derivatives of 1,2,4-triazole and their drug dosage forms, Kharkiv, 2013, 44 p.

Analiticheskaia khimiia v sozdanii, standartizatsii i kontrolie kachestva lekarstvennykh sredstv – Analytical Chemistry in the Development, Standardization and Quality Control of Medications / Ed. by V. P. Georgievskiy, Kharkiv: НТМТ, 2011, 1450 p.

Snyder L. R., Kirkland J. J., Glajch J. L. Practical HPLC Method Development, Wiley-Interscience, 1997, 542 p.

Varynskyi B. O. Problemy viiskovoi okhorony zdorovia: Zbirnyk naukovykh prats Ukrainskoi viiskovo-medychnoi akademii – Problems of military health care: Collection of scientific works of the Ukrainian military medical academy, 2015, No.43, pp.320-330.


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DOI: https://doi.org/10.24959/ophcj.15.859

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)