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

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...

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Main Authors: B. O. Varynskyi, A. G. Kaplaushenko
Format: Article
Language:English
Published: Zaporozhye State Medical University 2017-06-01
Series:Zaporožskij Medicinskij Žurnal
Subjects:
Online Access:http://zmj.zsmu.edu.ua/article/view/100947/97449
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spelling doaj-932c38add8904c319f4af92e9a223aa32020-11-25T01:14:20ZengZaporozhye State Medical UniversityZaporožskij Medicinskij Žurnal2306-41452310-12102017-06-013373380http://dx.doi.org/10.14739/2310-1210.2017.3.100947The 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 drugB. O. VarynskyiA. G. KaplaushenkoPurpose. 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. http://zmj.zsmu.edu.ua/article/view/100947/97449triazoleshigh pressure liquid chromatographypharmaceutical productsdrug contamination
collection DOAJ
language English
format Article
sources DOAJ
author B. O. Varynskyi
A. G. Kaplaushenko
spellingShingle B. O. Varynskyi
A. G. Kaplaushenko
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
Zaporožskij Medicinskij Žurnal
triazoles
high pressure liquid chromatography
pharmaceutical products
drug contamination
author_facet B. O. Varynskyi
A. G. Kaplaushenko
author_sort B. O. Varynskyi
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publisher Zaporozhye State Medical University
series Zaporožskij Medicinskij Žurnal
issn 2306-4145
2310-1210
publishDate 2017-06-01
description 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.
topic triazoles
high pressure liquid chromatography
pharmaceutical products
drug contamination
url http://zmj.zsmu.edu.ua/article/view/100947/97449
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