Validated stability-indicating methods for determination of cilostazol in the presence of its degradation products according to the ICH guidelines

Abstract

Sensitive and selective stability-indicating assay methods (SIAMs) are suggested for the determination of cilostazol (CIL) in the presence of its acid, alkaline and oxidative degradation products. Developing SIAMs is necessary to carry out any stability study. Stress testing of CIL was performed according to the International Conference on Harmonization (ICH) guidelines in order to validate the stability-indicating power of the analytical procedures. Stress testing showed that CIL underwent acid, alkaline and oxidative degradation; on the other hand, it showed stability towards photo- and thermal degradation. Two chromatographic SIAMs were developed, namely HPLC and HPTLC methods. The concentration range and the mean percentage recovery were 1.0–31.0 μg/ml and 99.96 ± 0.46 and 0.6–14.0 μg/spot and 99.88 ± 1.10 for HPLC and HPTLC methods, respectively. In addition, derivative spectrophotometric methods were developed in order to determine CIL in the presence of its acid degradation product; these were performed by using the third derivative spectra ( 3D) and the first derivative of the ratio spectra ( 1DD) methods. The linearity range and the mean percentage recovery were 2.0–34.0 μg/ml and 100.27 ± 1.20 for the ( 3D) method, while they were 2.0–30.0 μg/ml and 99.94 ± 1.18 for the ( 1DD) method. Also, two chemometric-assisted spectrophotometric methods, based on using partial least squares (PLS) and concentration residual augmented classical least squares method (CRACLS), for the determination of CIL were developed. Both methods were applied on zero order spectra of the mixtures of CIL and its acid degradation product, the mean percentage recovery was 100.03 ± 1.09 and 99.91 ± 1.27 for PLS and CRACLS, respectively. All methods were validated according to the International Conference on Harmonization (ICH) guidelines and applied on bulk powder and pharmaceutical formulations.