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An Improved HPLC Method with the Aid of a Chemometric Protocol: Simultaneous Determination of Atorvastatin and Its Metabolites in Plasma

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2013
1926.pdf (652.6Kb)
Authors
Crevar-Sakač, Milkica
Vujić, Zorica
Brborić, Jasmina
Kuntić, Vesna
Uskoković-Marković, Snežana
Article (Published version)
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Abstract
The aim of the present study was to optimize a chromatographic method for the analysis of atorvastatin (acid and lactone forms), ortho- and para-hydroxyatorvastatin by using an experimental design approach. Optimization experiments were conducted through a process of screening and optimization. The purpose of a screening design is to identify the factors that have significant effects on the selected chromatographic responses, and for this purpose a full 23 factorial design was used. The location of the true optimum was established by applying Derringer's desirability function, which provides simultaneously optimization of all seven responses. The ranges of the independent variables used for the optimization were content of acetonitrile in mobile phase (60-70%), temperature of column (30-40 C degrees) and flow rate (0.8-1.2 mL min(-1)). The influences of these independent variables were evaluated for the output responses: retention time of first peak (p-hydroxyatorvastatin) and of last ...peak (atorvastatin, lactone form), symmetries of all four peaks and relative retention time of p-hydroxyatorvastatin. The primary goal of this investigation was establishing a new simple and sensitive method that could be used in analysis of biological samples. The method was validated and successfully applied for determination of atorvastatin (acid and lactone forms) and its metabolites in plasma.

Keywords:
atorvastatin (acid and lactone) / ortho- and para-hydroxyatorvastatin / central composite design / Derringer's desirability function / HPLC
Source:
Molecules, 2013, 18, 3, 2469-2482
Publisher:
  • MDPI, Basel
Funding / projects:
  • Development of molecules with antiinflammatory and cardioprotective activity: structural modifications, modelling, physicochemical characterization and formulation investigations (RS-172041)

DOI: 10.3390/molecules18032469

ISSN: 1420-3049

PubMed: 23439563

WoS: 000316611700002

Scopus: 2-s2.0-84875606694
[ Google Scholar ]
9
5
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/1928
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Crevar-Sakač, Milkica
AU  - Vujić, Zorica
AU  - Brborić, Jasmina
AU  - Kuntić, Vesna
AU  - Uskoković-Marković, Snežana
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1928
AB  - The aim of the present study was to optimize a chromatographic method for the analysis of atorvastatin (acid and lactone forms), ortho- and para-hydroxyatorvastatin by using an experimental design approach. Optimization experiments were conducted through a process of screening and optimization. The purpose of a screening design is to identify the factors that have significant effects on the selected chromatographic responses, and for this purpose a full 23 factorial design was used. The location of the true optimum was established by applying Derringer's desirability function, which provides simultaneously optimization of all seven responses. The ranges of the independent variables used for the optimization were content of acetonitrile in mobile phase (60-70%), temperature of column (30-40 C degrees) and flow rate (0.8-1.2 mL min(-1)). The influences of these independent variables were evaluated for the output responses: retention time of first peak (p-hydroxyatorvastatin) and of last peak (atorvastatin, lactone form), symmetries of all four peaks and relative retention time of p-hydroxyatorvastatin. The primary goal of this investigation was establishing a new simple and sensitive method that could be used in analysis of biological samples. The method was validated and successfully applied for determination of atorvastatin (acid and lactone forms) and its metabolites in plasma.
PB  - MDPI, Basel
T2  - Molecules
T1  - An Improved HPLC Method with the Aid of a Chemometric Protocol: Simultaneous Determination of Atorvastatin and Its Metabolites in Plasma
VL  - 18
IS  - 3
SP  - 2469
EP  - 2482
DO  - 10.3390/molecules18032469
ER  - 
@article{
author = "Crevar-Sakač, Milkica and Vujić, Zorica and Brborić, Jasmina and Kuntić, Vesna and Uskoković-Marković, Snežana",
year = "2013",
abstract = "The aim of the present study was to optimize a chromatographic method for the analysis of atorvastatin (acid and lactone forms), ortho- and para-hydroxyatorvastatin by using an experimental design approach. Optimization experiments were conducted through a process of screening and optimization. The purpose of a screening design is to identify the factors that have significant effects on the selected chromatographic responses, and for this purpose a full 23 factorial design was used. The location of the true optimum was established by applying Derringer's desirability function, which provides simultaneously optimization of all seven responses. The ranges of the independent variables used for the optimization were content of acetonitrile in mobile phase (60-70%), temperature of column (30-40 C degrees) and flow rate (0.8-1.2 mL min(-1)). The influences of these independent variables were evaluated for the output responses: retention time of first peak (p-hydroxyatorvastatin) and of last peak (atorvastatin, lactone form), symmetries of all four peaks and relative retention time of p-hydroxyatorvastatin. The primary goal of this investigation was establishing a new simple and sensitive method that could be used in analysis of biological samples. The method was validated and successfully applied for determination of atorvastatin (acid and lactone forms) and its metabolites in plasma.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "An Improved HPLC Method with the Aid of a Chemometric Protocol: Simultaneous Determination of Atorvastatin and Its Metabolites in Plasma",
volume = "18",
number = "3",
pages = "2469-2482",
doi = "10.3390/molecules18032469"
}
Crevar-Sakač, M., Vujić, Z., Brborić, J., Kuntić, V.,& Uskoković-Marković, S.. (2013). An Improved HPLC Method with the Aid of a Chemometric Protocol: Simultaneous Determination of Atorvastatin and Its Metabolites in Plasma. in Molecules
MDPI, Basel., 18(3), 2469-2482.
https://doi.org/10.3390/molecules18032469
Crevar-Sakač M, Vujić Z, Brborić J, Kuntić V, Uskoković-Marković S. An Improved HPLC Method with the Aid of a Chemometric Protocol: Simultaneous Determination of Atorvastatin and Its Metabolites in Plasma. in Molecules. 2013;18(3):2469-2482.
doi:10.3390/molecules18032469 .
Crevar-Sakač, Milkica, Vujić, Zorica, Brborić, Jasmina, Kuntić, Vesna, Uskoković-Marković, Snežana, "An Improved HPLC Method with the Aid of a Chemometric Protocol: Simultaneous Determination of Atorvastatin and Its Metabolites in Plasma" in Molecules, 18, no. 3 (2013):2469-2482,
https://doi.org/10.3390/molecules18032469 . .

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