An accurate, precise, robust and sensitive method was developed for residual solvents determination by fast static headspace gas chromatography (HSGC) with flame ionization detector in Imatinib Mesylate API. Residual solvents in drug substances are quantified using gas chromatography with headspace. As per regulatory guidelines, residual solvents must be controlled for release any batches of active pharmaceutical ingredients (API). This paper includes the development and validation of HSGC method for the determination of residual solvents specifically methanol, acetone, dichloromethane, n-hexane, ethyl acetate and pyridine in Imatinib Mesylate API. Imatinib Mesylate is a specific inhibitor of BCR-ABL tyrosine kinase. DB-624 capillary column, 30 m long × 0.53 mm internal diameter, the 3 µm film thickness was used for analysis. To minimize degradation, injector temperature was set at 170 °C. The initial oven temperature was kept at 35 °C for 2 min and used ramp 1 at a rate of 4 °C min −1 to temperature of 80 °C hold for 0 min and used ramp 2 at a rate of 40 °C min −1 to a final temperature of 230 °C for 12 min hold time. Nitrogen was selected as a carrier gas. 1-Methyl-2-Pyrrolidinone (NMP) was used as a sample solvent. The method can be readily used to determine defined residual solvents present in a various range of APIs, intermediates, excipients and drug products.

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.