End-to-end Standardization of Original Medicines when Determining Related Impurities

Introduction. For tablets “Malоben, 60 mg” and “Etmaben, 300 mg”, permission was received to conduct phase I clinical trials, so they required a full cycle of research and standardization.Aim. Development of a unified analytical procedure for the determination of related impurities in samples (RS, A...

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Main Authors: Yu. E. Generalova, I. I. Terninko, A. B. Zelentsova
Format: Article
Language:Russian
Published: LLC Center of Pharmaceutical Analytics (LLC «CPHA») 2023-12-01
Series:Разработка и регистрация лекарственных средств
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Online Access:https://www.pharmjournal.ru/jour/article/view/1647
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author Yu. E. Generalova
I. I. Terninko
A. B. Zelentsova
author_facet Yu. E. Generalova
I. I. Terninko
A. B. Zelentsova
author_sort Yu. E. Generalova
collection DOAJ
description Introduction. For tablets “Malоben, 60 mg” and “Etmaben, 300 mg”, permission was received to conduct phase I clinical trials, so they required a full cycle of research and standardization.Aim. Development of a unified analytical procedure for the determination of related impurities in samples (RS, API, FPP) of Malоben and Ethmaben.Materials and methods. RSs were obtained at the Department of Organic Chemistry of the St. Petersburg State Chemical and Pharmaceutical University; the synthesis of APIs and the production of FPP were carried out on an industrial scale in pharmaceutical production. The studies were carried out on a Flexar liquid chromatograph (PerkinElmer, USA), equipped with a pump (formation of a gradient on the low-pressure side), an autosampler, a column thermostat, a UV detector and a chromatographic column Intersil® ODS-3V, 5 µm, 100 Å, 250 × 4, 6 (Phenomenex, Japan).Results and discussion. In the research, uniform optimal chromatographic conditions were selected using the HPLC method to determine the RP in RS, API and FPP of Maloben and Ethmaben. Column C18 250×4.6 mm, mobile phase 0.1% phosphoric acid and acetonitrile (gradient elution), flow rate 1 ml/min, sample volume 10 µl, UV detector (270 nm). They were validated in terms of specificity, linearity, detection limit, precision, robustness, and solution stability. Analytical concentration levels were selected for the formation of draft regulatory documents. Using the developed analytical technique, samples of RS, API and tablets of malоben and ethmaben were analyzed.Conclusion. A full cycle of research was carried out, an analytical methodology was developed and related impurities were identified in RS, API and FPP of Maloben and Ethmaben.
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spelling doaj-art-28c3ebfb3475480b8860949368db61a12025-08-20T03:59:04ZrusLLC Center of Pharmaceutical Analytics (LLC «CPHA»)Разработка и регистрация лекарственных средств2305-20662658-50492023-12-0112420921610.33380/2305-2066-2023-12-4-15731161End-to-end Standardization of Original Medicines when Determining Related ImpuritiesYu. E. Generalova0I. I. Terninko1A. B. Zelentsova2Saint-Petersburg State Chemical and Pharmaceutical UniversitySaint-Petersburg State Chemical and Pharmaceutical UniversitySaint-Petersburg State Chemical and Pharmaceutical UniversityIntroduction. For tablets “Malоben, 60 mg” and “Etmaben, 300 mg”, permission was received to conduct phase I clinical trials, so they required a full cycle of research and standardization.Aim. Development of a unified analytical procedure for the determination of related impurities in samples (RS, API, FPP) of Malоben and Ethmaben.Materials and methods. RSs were obtained at the Department of Organic Chemistry of the St. Petersburg State Chemical and Pharmaceutical University; the synthesis of APIs and the production of FPP were carried out on an industrial scale in pharmaceutical production. The studies were carried out on a Flexar liquid chromatograph (PerkinElmer, USA), equipped with a pump (formation of a gradient on the low-pressure side), an autosampler, a column thermostat, a UV detector and a chromatographic column Intersil® ODS-3V, 5 µm, 100 Å, 250 × 4, 6 (Phenomenex, Japan).Results and discussion. In the research, uniform optimal chromatographic conditions were selected using the HPLC method to determine the RP in RS, API and FPP of Maloben and Ethmaben. Column C18 250×4.6 mm, mobile phase 0.1% phosphoric acid and acetonitrile (gradient elution), flow rate 1 ml/min, sample volume 10 µl, UV detector (270 nm). They were validated in terms of specificity, linearity, detection limit, precision, robustness, and solution stability. Analytical concentration levels were selected for the formation of draft regulatory documents. Using the developed analytical technique, samples of RS, API and tablets of malоben and ethmaben were analyzed.Conclusion. A full cycle of research was carried out, an analytical methodology was developed and related impurities were identified in RS, API and FPP of Maloben and Ethmaben.https://www.pharmjournal.ru/jour/article/view/1647end-to-end standardizationoriginal drugsrelated impuritieshplcvalidation
spellingShingle Yu. E. Generalova
I. I. Terninko
A. B. Zelentsova
End-to-end Standardization of Original Medicines when Determining Related Impurities
Разработка и регистрация лекарственных средств
end-to-end standardization
original drugs
related impurities
hplc
validation
title End-to-end Standardization of Original Medicines when Determining Related Impurities
title_full End-to-end Standardization of Original Medicines when Determining Related Impurities
title_fullStr End-to-end Standardization of Original Medicines when Determining Related Impurities
title_full_unstemmed End-to-end Standardization of Original Medicines when Determining Related Impurities
title_short End-to-end Standardization of Original Medicines when Determining Related Impurities
title_sort end to end standardization of original medicines when determining related impurities
topic end-to-end standardization
original drugs
related impurities
hplc
validation
url https://www.pharmjournal.ru/jour/article/view/1647
work_keys_str_mv AT yuegeneralova endtoendstandardizationoforiginalmedicineswhendeterminingrelatedimpurities
AT iiterninko endtoendstandardizationoforiginalmedicineswhendeterminingrelatedimpurities
AT abzelentsova endtoendstandardizationoforiginalmedicineswhendeterminingrelatedimpurities