The development and validation of HPLC-DMD method for intermediate products impurities determination of morpholinium 2-((4-(2-methoxyphenyl)-5-(pyridine-4-yl)-4H-1,2,4-triazole-3-yl)thio)acetate in bulk drug
DOI:
https://doi.org/10.14739/2310-1210.2017.3.100947Keywords:
triazoles, high pressure liquid chromatography, pharmaceutical products, drug contaminationAbstract
Purpose. A development and validation of new sensitive, high efficient and selective HPLC determination method of intermediates technological contaminations in bulk drug of morpholin-4-ium 2-((4-(2-methoxyphenyl)-5-(pyridine-4-yl)-4H-1,2,4-triazole-3-yl)thio)acetate (active pharmaceutical ingredient – API).
Materials and methods. LC System was Agilent 1260 Infinity (degasser, binary pump, autosampler, column thermostat, diode array detector) Open LAB CDS Software. Column was Zorbax SB-C18; 30 mm × 4.6 mm; 1.8 µm. Injection volume was 5 µL. Isocratic mode. The mobile phase was water/acetonitrile (84:16) with 0.1 % methanoic acid. Standard samples were morpholinium 2-((4-(2-methoxyphenyl)-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)thio)acetate, pyridine-4-carbohydrazide, 2-isonicotinoyl-N-(2-methoxyphenyl)hydrazine-1-carbothioamide, 4-(2-methoxyphenyl)-5-(pyridin-4-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione.
Results. A new criterion for choosing chromatographic separation condition was proposed. It is absolute value of retention factors differences (|Δk|). Six different curves which show dependence of absolute value of retention factors differences (|Δk|) for each compound from the acetonitrile in mobile phase was built at registration of the signal on diode-array detector. A chromatographic separation optimal condition of impurities and API in drug bulk was found with satisfied resolution. UV spectra of API and impurities were determined. Method of the quantitative determination of the impurities was elaborated. Total sample preparation uncertainty was predicted. Method was validated according to European and Ukrainian Pharmacopeia. It was applied for real bulk drug samples.
Conclusions. Chromatography separation of impurities and API was done. A method was complied with linearity criteria, specificity, precision and accuracy. The results of impurity determination in bulk drug indicated, that method can be used for the quality control of bulk drug.
References
Kаplаushenkо, A. H. (2012) Syntez, budova i biolohichna aktyvnist pokhidnykh 4-mono-ta 4,5-dyzamishchenykh 1,2,4-triazol-3-tionu (Dis… dokt. med. nauk). [Synthesis, structure and biological activity of 4-mono- and 4,5-disubstituted 1,2,4-triazoles-3-thione. Dr. med. sci. diss.]. Zaporizhzhia. [in Ukrainian].
Kaplaushenko, A. H., Panasenko, O. I., Knysh, Ye. H., Vasiuk, S. O., & Tarkhanova, O. O. (2009). Rozrobka metodiv yakisnoho ta kilkisnoho vyznachennia morfolinii 2-(5-(4-pirydyl)-4-(2-metoksyfenil)-1,2,4-tryazol-3-iltio) atsetatu [Development of methods for qualitative and quantitative determination morpholino 2-(5-(4-pyridyl)-4-(2-methoxyphenyl)-1,2,4-triazole-3-ylthio) acetate]. Zaporozhye medical journal, 1, 79–81. [in Ukrainian]
(2013). European Pharmacopoeia. Strasbourg, France: Council of Europe.
Derzhavna Farmakopeia Ukrainy. Dopovnennia 1. (2004) [The State Pharmacopoeia of Ukraine. Vol. 1]. Kharkiv: RІREH. [in Ukrainian].
Varynskyi, B. O. (2015) Doslidzhennia kharakterystyk utrymuvannia riadu hidrazydiv karbonovykh kyslot i hidrazynokarbotioamidiv, vykhidnykh rechovyn pry syntezi substantsii dlia vyhotovlennia likarskykh zasobiv metodom VERKh-UF-ESI-MS [Study retention characteristics of series hydrazides of carboxylic acids and hydrazynocabothioamids, starting materials in the synthesis of bulk drugs for manufacturing of the pharmaceutical preparations by HPLC-UV-ESI-MS]. Problemy viiskovoi okhorony zdorovia. Zbirnyk naukovykh prats Ukrainskoi viiskovo-medychnoi akademii, 43, 320–330. [in Ukrainian].
Varynskyi, B. O., Knysh, Ye. G., Parchenko, V. V., Panasenko, O. I., & Kaplaushenko, A. G. (2015) Vyvchennya zakonomirnostey utrymuvannya potentsiynykh llikars'kykh substantsiy ryadu 1,2,4-triazol-3-iltioatsetatnykh kyslot ta yikh soley metodom VERKh/DMD-MS [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] Zhurnal orhanichnoi ta farmatsevtychnoi khimii, 13, 4(52), 68–72. [in Ukrainian].
Varynskyi, B. O. (2016) Vyvchennia metodom VERKh-DMD-MS zakonomirnostei utrymuvannia riadu 1,2,4-triazol-3-tioniv – napivproduktiv v syntezi aktyvnykh farmatsevtychnykh inhrediientiv [Optimization of the detection conditions for the series of 1,2,4-triazole-3-thiones for FIA-ESI-MS and HPLC-ESI-MS]. Farmakom, 1, 32–40. [in Ukrainian].
Derzhavna Farmakopeia Ukrainy (2001) [The State Pharmacopoeia of Ukraine]. Kharkiv: RІREH. [in Ukrainian].
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