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

2013
Authors
Crevar-Sakač, Milkica
Vujić, Zorica

Brborić, Jasmina

Kuntić, Vesna
Uskoković-Marković, Snežana

Article (Published version)
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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 / HPLCSource:
Molecules, 2013, 18, 3, 2469-2482Publisher:
- MDPI, Basel
Funding / projects:
DOI: 10.3390/molecules18032469
ISSN: 1420-3049
PubMed: 23439563
WoS: 000316611700002
Scopus: 2-s2.0-84875606694
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Institution/Community
PharmacyTY - 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 . .