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A Stability-Indicating HPLC-DAD Method for Determination of Stiripentol: Development, Validation, Kinetics, Structure Elucidation and Application to Commercial Dosage Form

Hany W. Darwish, Ali S. Abdelhameed, Mohamed I. Attia, Ahmed H. Bakheit, Nasr Y. Khalil, and Abdulrahman A. Al-Majed

Abstract

A rapid, simple, sensitive, and accurate isocratic reversed-phase stability-indicating high performance liquid chromatography method has been developed and validated for the determination of stiripentol and its degradation product in its bulk form and pharmaceutical dosage form. Chromatographic separation was achieved on a Symmetry C18 column and quantification was achieved using photodiode array detector (DAD). The method was validated in accordance with the ICH requirements showing specificity, linearity (range of 1–25 μg/mL), precision (relative standard deviation lower than 2%), accuracy (mean recovery), limits of detection and quantitation (LOD = 0.024 and LOQ = 0.081 μg/mL), and robustness. Stiripentol was subjected to various stress conditions and it has shown marked stability under alkaline hydrolytic stress conditions, thermal, oxidative, and photolytic conditions. Stiripentol degraded only under acidic conditions, forming a single degradation product which was well resolved from the pure drug with significantly different retention time values. This degradation product was characterized by 1H-NMR and 13C-NMR spectroscopy as well as ion trap mass spectrometry. The results demonstrated that the method would have a great value when applied in quality control and stability studies for stiripentol.

Conclusions

The present study represents the first report that deals with the development and validation of a stability-indicating HPLC-DAD method for determination of STP. This study is a typical example of development of a stability-indicating assay, established following the recommendations of ICH guidelines. The proposed method showed acceptable accuracy, precision, and selectivity. From the economical point of view, the method involved the native UV-absorbing property of STP, rather than expensive derivatizing analytical reagents. STP showed great stability at the various stress conditions (thermal, alkaline, oxidative, and photodegradation). A single degradation product, DSTP, was only formed with the exposure of STP to acidic degradation using HCl. Structure elucidation of the acidic degradation product using 1H-NMR, 13C-NMR, and ion trap mass spectrometry revealed substitution of OH functionality of STP with chloride following treatment of STP with hydrochloric acid. Additionally, kinetic study of the acidic degradation reaction demonstrated that STP undergoes first-order kinetics. The method is suitable for the determination of STP in bulk and capsule form without any interference from the degradation products, and it is recommended for routine use in quality control industry laboratories.

Citation: Hany W. Darwish, Ali S. Abdelhameed, Mohamed I. Attia, Ahmed H. Bakheit, et al. “A Stability-Indicating HPLC-DAD Method for Determination of Stiripentol: Development, Validation, Kinetics, Structure Elucidation and Application to Commercial Dosage Form,”Journal of Analytical Methods in Chemistry, vol. 2014, Article ID 638951, 10 pages, 2014. doi:10.1155/2014/638951
Editor: Josep Esteve-Romero
Received: 24 August 2014; Accepted 25 September 2014; Published 14 October 2014
Copyright © 2014 Hany W. Darwish et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Acknowledgments:
The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for its funding of this Research Group No. RG-1435-025.

Conflict of Interests: The authors declare no conflict of interests.


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