Application of Factorial and Doehlert Designs for the Optimization of the Simultaneous Separation and Determination of Antimigraine Drugs in Pharmaceutical Formulations by RP-HPLC-UV

Sami Jebali,Mohamed Radhouen Louhaichi,Chaouki Belgacem,Latifa Latrous El Atarche,Senda Bahri

doi:10.1155/2019/9685750

Abstract

A sensitive, precise, accurate, and specific isocratic reversed-phase high-performance liquid chromatographic (RP-HPLC) method for the simultaneous separation and determination of zolmitriptan, naratriptan, dihydroergotamine, ketotifen, and pizotifen in pharmaceutical formulations has been developed and validated. An experimental design was applied for the optimization of the chromatographic parameters. A two-level full factorial 2k was used for studying the interaction between the variables to be optimized: the percentage of acetonitrile in the mobile phase, mobile-phase pH, nature of the buffer, and column oven temperature. The most significant parameters are the percentage of acetonitrile and the mobile-phase pH. These significant parameters were optimized using the Doehlert matrix. The optimum separation was achieved by means of a Waters XBridge C18 column (250 mm × 4.6 mm, 5 μm) with a mobile phase consisting of acetonitrile and a 10 mM sodium perchlorate buffer (38 : 62, v/v) at a flow rate of 1.0 mL·min−1 and UV detection at 220 nm. The selectivity, method linearity, accuracy, and precision were examined as part of the method validation. The described method shows excellent linearity over a range of 30 to 70 μg·mL−1 for all compounds with correlation coefficients higher than 0.995. The standard deviations of the intraday and interday precision were between 0.75 and 1.94%. The validated method was successfully applied to perform routine analysis of these compounds in different pharmaceutical products such as syrups and tablets. In the presence of some preservatives, it was found that there were no peaks at the related peak locations.

Highlights

Migraine is the third most prevalent and sixth most disabling medical illness in the world
Application of the Method. e potential of the method for the analysis of pharmaceutical formulations from the local market such as tablets and syrup has been demonstrated. e outcome of this study has shown a good agreement between the experimental and label claims (Table 8). e recovery percentage, with respect to the label claims, ranged between 97.45 and 102.60%, indicating a good accuracy of the proposed method
Applying fractional factorial design (FFD) with the purpose of screening of variables and Doehlert design for optimization of the screened variables, the simultaneous determination of Zol, Nara, DHE, and pizotifen malate (Pizo) in pharmaceutical preparations was conducted by reversed-phase high-performance liquid chromatography (RP-High-performance liquid chromatography (HPLC))

Summary

Introduction

Migraine is the third most prevalent and sixth most disabling medical illness in the world. It consists of headache attacks lasting 4–72 h, of moderate to severe intensity, associated with nausea and photo- and phonophobia [1, 2]. HT13/1D receptor agonists, a collectively known triptan drug class [5, 6]. Ey work by stimulating serotonin receptors in the brain. Zolmitriptan (Zol), naratriptan (Nara), dihydroergotamine (DHE), and pizotifen malate (Pizo) are recommended as firstline drugs for acute migraine treatment. Clinical studies have shown Zol to be effective and well tolerated [13].

Methods

Results

Conclusion