Greenness assessment profile of experimentally designed chromatographic method for the simultaneous analysis of ofloxacin and racecadotril in the presence of racecadotril impurities

Experimental design beats the conventional one variable at a time (OVAT) to improve the chromatographic separations with lowest consumption of resources and maximum acceptable results for the separated peaks. Experimental design using face-centred composite design was utilized during method optimiza...

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Main Authors: Nada Nabil, Ghada A. Sedik, Hala E. Zaazaa, Sally S. El-Mosallamy
Format: Article
Language:English
Published: Elsevier 2025-12-01
Series:Talanta Open
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Online Access:http://www.sciencedirect.com/science/article/pii/S266683192500089X
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author Nada Nabil
Ghada A. Sedik
Hala E. Zaazaa
Sally S. El-Mosallamy
author_facet Nada Nabil
Ghada A. Sedik
Hala E. Zaazaa
Sally S. El-Mosallamy
author_sort Nada Nabil
collection DOAJ
description Experimental design beats the conventional one variable at a time (OVAT) to improve the chromatographic separations with lowest consumption of resources and maximum acceptable results for the separated peaks. Experimental design using face-centred composite design was utilized during method optimization to obtain the highest level of resolution with the fewest number of experimental trials for the determination of ofloxacin (OFLU) and racecadotril (RAC) in the presence of RAC impurities. The two independent variables were the pH of solvent A (0.10 % triethyl amine (pH 7 by orthophosphoric acid)) and its percentage in the mobile phase. RAC combined with OFLU is mainly used to treat diarrhoea in children. RAC has several impurities; among them is racecadotril impurity A (RAC-A) which was reported as a toxic impurity of RAC, additionally, RAC can be oxidized to racecadotril oxidative degradation product (RAC-Deg). Chromatographic separation was accomplished using Inertsil ODS column (150 mm, 4.6 mm, 5 μm) and isocratic elution using 0.10 % triethyl amine (pH 7 by orthophosphoric acid) (solvent A): methanol (solvent B) (20:80 v/v) as a mobile phase at a flow rate of 1.00 mL/min and UV detection at 240 nm. Sharp, well-resolved peaks for RAC-Deg, RAC-A, OFLU and RAC were obtained with retention times of 1.70, 2.06, 7.11, and 8.98 min, respectively. Method validation was carried out according to ICH guidelines and linearity was achieved in the ranges of 2.00–20.00 and 3.00–25.00 µg/mL for RAC and OFLU, respectively. The ecological impact of the presented technique was assessed utilizing the Analytical GREEnness Metric Approach and Software (AGREE) as an evaluation tool. The new approach shown high accuracy, selectivity, precision, and environmental friendliness in determining the mentioned drugs in pharmaceutical formulations. It is suitable for routine analysis of the drugs in quality control laboratories.
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spelling doaj-art-c24555b2b8d3477496d100fba068b3b22025-08-20T03:55:17ZengElsevierTalanta Open2666-83192025-12-011210048710.1016/j.talo.2025.100487Greenness assessment profile of experimentally designed chromatographic method for the simultaneous analysis of ofloxacin and racecadotril in the presence of racecadotril impuritiesNada Nabil0Ghada A. Sedik1Hala E. Zaazaa2Sally S. El-Mosallamy3Analytical Chemistry Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Entertainment Area, Badr City, Cairo 11829, EgyptPharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt; Corresponding author.Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, EgyptPharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, EgyptExperimental design beats the conventional one variable at a time (OVAT) to improve the chromatographic separations with lowest consumption of resources and maximum acceptable results for the separated peaks. Experimental design using face-centred composite design was utilized during method optimization to obtain the highest level of resolution with the fewest number of experimental trials for the determination of ofloxacin (OFLU) and racecadotril (RAC) in the presence of RAC impurities. The two independent variables were the pH of solvent A (0.10 % triethyl amine (pH 7 by orthophosphoric acid)) and its percentage in the mobile phase. RAC combined with OFLU is mainly used to treat diarrhoea in children. RAC has several impurities; among them is racecadotril impurity A (RAC-A) which was reported as a toxic impurity of RAC, additionally, RAC can be oxidized to racecadotril oxidative degradation product (RAC-Deg). Chromatographic separation was accomplished using Inertsil ODS column (150 mm, 4.6 mm, 5 μm) and isocratic elution using 0.10 % triethyl amine (pH 7 by orthophosphoric acid) (solvent A): methanol (solvent B) (20:80 v/v) as a mobile phase at a flow rate of 1.00 mL/min and UV detection at 240 nm. Sharp, well-resolved peaks for RAC-Deg, RAC-A, OFLU and RAC were obtained with retention times of 1.70, 2.06, 7.11, and 8.98 min, respectively. Method validation was carried out according to ICH guidelines and linearity was achieved in the ranges of 2.00–20.00 and 3.00–25.00 µg/mL for RAC and OFLU, respectively. The ecological impact of the presented technique was assessed utilizing the Analytical GREEnness Metric Approach and Software (AGREE) as an evaluation tool. The new approach shown high accuracy, selectivity, precision, and environmental friendliness in determining the mentioned drugs in pharmaceutical formulations. It is suitable for routine analysis of the drugs in quality control laboratories.http://www.sciencedirect.com/science/article/pii/S266683192500089XHPLCRacecadotrilOfloxacinExperimental design
spellingShingle Nada Nabil
Ghada A. Sedik
Hala E. Zaazaa
Sally S. El-Mosallamy
Greenness assessment profile of experimentally designed chromatographic method for the simultaneous analysis of ofloxacin and racecadotril in the presence of racecadotril impurities
Talanta Open
HPLC
Racecadotril
Ofloxacin
Experimental design
title Greenness assessment profile of experimentally designed chromatographic method for the simultaneous analysis of ofloxacin and racecadotril in the presence of racecadotril impurities
title_full Greenness assessment profile of experimentally designed chromatographic method for the simultaneous analysis of ofloxacin and racecadotril in the presence of racecadotril impurities
title_fullStr Greenness assessment profile of experimentally designed chromatographic method for the simultaneous analysis of ofloxacin and racecadotril in the presence of racecadotril impurities
title_full_unstemmed Greenness assessment profile of experimentally designed chromatographic method for the simultaneous analysis of ofloxacin and racecadotril in the presence of racecadotril impurities
title_short Greenness assessment profile of experimentally designed chromatographic method for the simultaneous analysis of ofloxacin and racecadotril in the presence of racecadotril impurities
title_sort greenness assessment profile of experimentally designed chromatographic method for the simultaneous analysis of ofloxacin and racecadotril in the presence of racecadotril impurities
topic HPLC
Racecadotril
Ofloxacin
Experimental design
url http://www.sciencedirect.com/science/article/pii/S266683192500089X
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AT halaezaazaa greennessassessmentprofileofexperimentallydesignedchromatographicmethodforthesimultaneousanalysisofofloxacinandracecadotrilinthepresenceofracecadotrilimpurities
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