Abstrakt

Different stability-indicating methods for the determination of quetiapine fumarate

Nesrin K.Ramadan, Afaf O.Mohamed, Roaida M.Fouad, Azza A.Moustafa

Five accurate, precise and sensitive methods were developed for the determination of Quetiapine fumarate (QF) in presence of its degradation product. Method (A) was based on second derivative spectrophotometry 2D, then measuring the amplitude at 266 nm. Method (B) was depended on measuring the peak amplitudes of the first derivative of the ratio spectra 1DD at 244, 285 and 344 nm. Method (C) was based on the separation of the drug from its oxidized degradation product followed by densitometric measurement of the intact drug band at 302 nm. The separation was carried out on Fluka TLC plates of silica gel 60 F254 using ethyl acetate/ methanol /10% ammonium hydroxide (8.5:1:0.5 by volume) as a mobile phase. Method (D) was high performance liquid chromatographic one, separation by HPLC was achieved using an Eclipse XDB C18RP-column and methanol / water in a ratio of 80:20 (v/v) as a mobile phase. The flow rate was 1ml/min. Method (E) was based on the reaction of QF with P-Chloranilic acid (PCA) in presence of its degradation product. Linearities were obtained in concentration range 10 – 60 g/ml in case of methods (A) and (B). While in case of methods (C) and (D), linearities were obtained in concentration range of 4-20 g/band and 1-20 g/ml respectively. While in method (E), the linearity was achieved in the range of 40-400 g/ml. In method (A), the mean percentage recovery was 99.9 ± 0.6%. In method (B) the mean percentage recoveries were 99.9 ± 0.4%, 99.2 ± 0.8% and 99.4 ± 0.8% at 244, 285 and 344 m respectively. Method (C) showed percentage mean recovery of 99.9 ± 0.7%, while in methods (D) and (E) were 99.8 ± 0.7% and 99.9 ± 0.4% respectively. The degradation product was obtained in oxidative stress condition, separated, and identified by IR and MS spectral analysis, from which the degradation product was confirmed, and the degradation pathway was suggested. The five methods were found to be specific for QF in presence of different concentration % of its degradation product. The proposed methods were validated according to ICH guidelines Q2 (R1). The five proposed methods were successfully applied for the determination of QF in Seroquel tablets. Statistical comparison between the results obtained by these methods and that obtained by the manufacturer method for the determination of the drug was done, and it was found that there was no significant differences between them.