Stability indicating RP-HPLC-UV method for quantitative estimation of isomer and other organic impurities of atopic dermatitis drug abrocitinib in drug substance and pharmaceutical dosage form using quality by design (QbD) approach

Abstract

A modest, reliable, robust, stability-indicating RP-HPLC-UV method was developed and validated following ICH Q2(R2) for the separation and quantification of isomer and other organic impurities of Abrocitinib (Janus kinase inhibitor). Quality by design (QbD) approach was used to achieve the desired specifications. The chromatographic separation was achieved for impurities method of Abrocitinib within 35 min of chromatographic run time on Agilent ZORBAX Eclipse plus C18 150*4.6 mm, 3.5 µm column with gradient elution mode: time (min)/B (%): 0.01/0, 2.5/15, 8.0/20, 15.0/40, 20.0/50, 25.0/50, 25.1/0, 35.0/0 with mobile phase-A (MP-A): 10 mmol/L CH3COONH4 and acetonitrile with the ratio of 900:100 (v/v), mobile phase-B (MP-B): 10 mmol/L CH3COONH4 and acetonitrile with the ratio of 100: 900 (v/v). The detection wavelength, mobile phase flow rate, column temperature, and injection volume were used at 287 nm, 1.0 mL/min, 40 °C, and 20 µl respectively. Utilizing forced degradation and mass balance investigations, the new method’s stability-indicating properties were assessed. The developed method was validated as per ICH and found to be specific, precise, rugged, robust, accurate, linear, and with a limit of quantification values,0.0359 µg/mL for the impurity IMP-A, 0.0192 µg/mL for the impurity IMP-B, 0.0322 µg/mL for the impurity IMP-C and 0.0201 µg/mL for abrocitinib.