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• Crevar-Sakač, M
• Vujić, Z
• Brborić, J
• Kuntić, V
• Uskoković-Marković, S
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• Crevar-Sakač, M
• Vujić, Z
• Brborić, J
• Kuntić, V
• Uskoković-Marković, S
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• Crevar-Sakač, M
• Vujić, Z
• Brborić, J
• Kuntić, V
• Uskoković-Marković, S

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Molecules 2013, 18(3), 2469-2482; doi:10.3390/molecules18032469

Article

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

Milkica Crevar-Sakač ¹ , Zorica Vujić ¹ , Jasmina Brborić ¹ , Vesna Kuntić ²  and Snežana Uskoković-Marković ^3,*

¹ Department of Pharmaceutical Chemistry, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, Belgrade 11221, Serbia ² Department of Physical Chemistry, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, Belgrade 11221, Serbia ³ Department of Analytical Chemistry, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, Belgrade 11221, Serbia

* Author to whom correspondence should be addressed.

Received: 31 December 2012; in revised form: 23 January 2013 / Accepted: 25 January 2013 / Published: 25 February 2013

Download PDF Full-Text [653 KB, uploaded 25 February 2013 11:37 CET]

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) 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

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