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
This study presents the first documented development and validation of a stability-indicating HPLC-DAD method for the accurate determination of STP (substance). Following the recommendations of ICH guidelines, this study exemplifies the creation of a stability-indicating assay. The proposed method demonstrates satisfactory accuracy, precision, and selectivity. Notably, the method utilizes the inherent UV-absorbing property of STP, eliminating the need for costly derivatizing analytical reagents, making it economically advantageous. STP exhibits excellent stability under various stress conditions such as thermal, alkaline, oxidative, and photodegradation. Only one degradation product, DSTP, is formed when STP is exposed to acidic degradation with HCl. Through the use of 1H-NMR, 13C-NMR, and ion trap mass spectrometry, the structure of the acidic degradation product was determined, indicating substitution of the OH functionality of STP with chloride in the presence of hydrochloric acid. Additionally, a kinetic study of the acidic degradation reaction revealed that STP follows first-order kinetics. The developed method is suitable for the quantification of STP in both bulk and capsule form, without any interference from degradation products, making it highly recommended for routine use in quality control laboratories within the industry.
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.
