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...
Main Authors: | , |
---|---|
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 |
id |
doaj-932c38add8904c319f4af92e9a223aa3 |
---|---|
record_format |
Article |
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 |
work_keys_str_mv |
AT bovarynskyi thedevelopmentandvalidationofhplcdmdmethodforintermediateproductsimpuritiesdeterminationofmorpholinium242methoxyphenyl5pyridine4yl4h124triazole3ylthioacetateinbulkdrug AT agkaplaushenko thedevelopmentandvalidationofhplcdmdmethodforintermediateproductsimpuritiesdeterminationofmorpholinium242methoxyphenyl5pyridine4yl4h124triazole3ylthioacetateinbulkdrug AT bovarynskyi developmentandvalidationofhplcdmdmethodforintermediateproductsimpuritiesdeterminationofmorpholinium242methoxyphenyl5pyridine4yl4h124triazole3ylthioacetateinbulkdrug AT agkaplaushenko developmentandvalidationofhplcdmdmethodforintermediateproductsimpuritiesdeterminationofmorpholinium242methoxyphenyl5pyridine4yl4h124triazole3ylthioacetateinbulkdrug |
_version_ |
1725157415051067392 |