Stability Indicating RP-HPLC Method for the Analysis of Dacomitinib and its Related Impurities in Bulk and Oral Solid Dosage Formulations

Abstract

Dacomitinib is an epidermal growth factor receptor inhibitor prescribed for the treatment of metastatic non small-cell lung carcinoma. There are no reported significant official of HPLC methods that resolve the impurities and degradation products generated during stability studies. Therefore, an isocratic RP-HPLC-UV method was developed for the determination of Dacomitinib in the presence of its related impurities and degradation products. The separation of Dacomitinib, impurity 1 and 2 was achieved on Agilent ZORBAX Eclipse (250×4.6 mm; 5 µ id) column as stationary phase, 0.1M sodium perchlorate at pH 5.6, acetonitrile as mobile phase in the ratio of 20:80 (V/V) at a flow rate of 1.0 mL/min in isocratic condition as mobile phase and UV detection was carried at 253 nm. In the optimised conditions, well resolved and retained peaks were observed at a retention time of 5.8 min, 4.0 min and 7.7 min for Dacomitinib, impurity 1 and 2 respectively. In the developed method, a very sensitive detection limit of 0.06 and 0.025 µg/mL was observed for impunity 1 and 2 respectively. The calibration was observed to be within the concentration range of 20 – 200 µg/mL for Dacomitinib and 0.2 – 2 µg/mL for impurity 1 and 2. The proposed method was used to investigate the effective separation of impurities along with degradation compounds formed under different degradative conditions and confirms that the method is stability indicating. Hence it can be concluded that the method was found to be simple, sensitive, specific, accurate, linear, precise, rugged, robust, and useful for estimation and characterizing the stability of Dacomitinib, impurity 1 and 2.