Assessment by HPLC of the degradation behavior of acitretin under hydrolytic,oxidative,photolytic and thermal stress conditions

Acitretin is a photosensitive oral retinoid with very limited data available on its degradation.The official HPLC method for acitretin determination was insufficient to resolve the degradation products generated during stability studies.Therefore,an isocratic RP-HPLC-UV method was developed for the determination of acitretin in the presence of its related impurities and degradation products.Efficient chromatographic separation was achieved on a Thermo beta-basic column C18(100 mm
4.6 mm,5μm)with mobile phase containing 0.3%(v/v)glacial acetic acid with acetonitrile(ACN)and isopropyl alcohol(IPA)in an isocratic ratio of 70:30 at a flow rate of 1.0 mL/min with the eluent monitored at 360 nm.The method was validated for specificity,linearity,precision,accuracy and robustness.The calibration plot was linear over the concentration range of 50-150μg/mL with a correlation coefficient(r2)of 0.999.The proposed method was used to investigate the degradation kinetics of acitretin under the different degradative conditions.The degradation rate constant(K),half-life(t1/2),and t90 were calculated.Degradation of acitretin followed pseudo-first-order kinetics.The drug was found to be less stable under acidic and photolytic degradation conditions:the photolytic degradation constants for acitretin in sunlight and UV light were 0.002698%and 0.0008402%min1,respectively.The LOD for acitretin and the known impurities were at a level below 0.02%.The method shows consistent recoveries for ACTR(99.8%-101.2%)and also for its known impurities(97.2-101.3%).The method was found to be accurate,precise,linear,specific,sensitive,rugged,robust,and useful for characterizing the stability of this chemical.