Development of Chromatographic Method for Determination of Impurities in Solid Dispersion of Dasatinib

Abstract

An accurate, fast, precise and economic gradient reverse phase high performance liquid chromatographic (RP-HPLC) method was developed for quantitative determination of process and degradation related impurities in the solid dispersion of dasatinib drug substance. The optimum separation was achieved by Sunniest C18, 250 x 4.6 mm, 5 µm column at 35 °C. The mobile phase A was 20 mM ammonium acetate buffer (pH 5.0) and mobile phase B was composed of methanol:buffer:acetonitrile (90:5:5) (%, v/v/v); the chromatographic analysis was performed with gradient condition detecting the related substances at wavelength 310 nm at flow rate of 1.2 mL/min. The resolution for dasatinib and six related components was found to be greater than 2.0 for any pair of impurities. The stability indicating nature of the method was demonstrated by performing force degradation studies. Significant degradation was observed when the solid dispersion of dasatinib was subjected to oxidation, thermal and photo degradation, while the drug substance was stable in acid and alkali degradation. Relative standard deviation obtained for the system precision and method precision studies was less than 5%. The accuracy of the method was demonstrated by performing recovery studies through spiking studies. The developed method was validated for linearity, specificity, accuracy, precision, limit of detection, limit of quantitation and robustness studies; it can be used in quality control for commercialization of solid dispersion of dasatinib drug substances and performing stability studies.

Simultaneous separation of atenolol enantiomers and its acid/alkaline degradation impurities on mixed‐mode chiral ligand exchange stationary phases

“…As per the International Conference on Harmonization (ICH) Guideline Q1A(R2), the shelf life of medicine is determined by its stability studies 34 . To determine the stability and quality control, forced degradation is usually carried out in new drug development.…”

“…As per the International Conference on Harmonization (ICH) Guideline Q1A(R2), the shelf life of medicine is determined by its stability studies. 34 To determine the stability and quality control, forced degradation is usually carried out in new drug development. Different from content assay of the major drug ingredient, forced degradation test focus on the determination of the impurities, which plays an important role in ensuring the safety of the clinical medication.…”

Pretreatment and analysis techniques development of TKIs in biological samples for pharmacokinetic studies and therapeutic drug monitoring

“…Therefore, the HPLC-UV/PDA method emerges as a rapid, economical, simple, accurate, precise, and reliable analytical technique for routine quantification of TKIs in clinical samples. Structurally speaking, TKIs exhibit characteristic absorption ranges at the wavelength of 230–326 nm for imatinib [ [99] , [100] , [101] , [102] , [103] , [104] , [105] ], 260–325 nm for dasatinib [ [106] , [107] , [108] , [109] , [110] ], 235–265.5 nm for sorafenib [ 30 , 102 , 111 ], 265–385 nm for nintedanib [ 112 , 113 ], 277 nm for sunitinib [ 114 ], etc. Sakhi et al [ 30 ] developed a sensitive HPLC/UV method for the determination of sorafenib in standard solutions and spiked plasma.…”