药物分析学报

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Validated Stability-Indicating UPLC Method for Determination of Dapoxetine and Fluoxetine: Characterization of Their Hydrolytic Degradation Products, Kinetic Study and Application in Pharmaceutical Dosage Forms

Suzan Mahmoud Soliman, Heba MY El-Agizy and Abd El Aziz El Bayoumi

New isocratic stability-indicating reversed phase UPLC method was developed for determination of two antidepressant drugs dapoxetine hydrochloride (DAP) and fluoxetine hydrochloride (FLX) in the presence of their hydrolytic degradation products namely; (+)-N, N-dimethyl-1-phenyl-3-propanolamine (DAP Deg I), N-methyl- 3-hydroxy-3-phenyl propyl amine (FLX DegI), α, α, α-Trifluorotoluene (FLX Deg II) and application in their pharmaceutical dosage forms.

UPLC method using small sub-1.8 μm particle was developed for separation and determination of the selected drugs using Agilent Eclipse XDB C18 (50 mm x 2.1 mm i.d., 1.8 μm) column. Upon using UPLC, the run time could be reduced 5-fold and the solvents consumption decreased 10 tims. Quantification is achieved by detection wavelength at 210 nm, based on peak area. The linear ranges were 0.05-100 μg/mL and 0.30-100 μg/mL with LOD of 0.01 and 0.09 μg mL-1 and mean recoveries of 99.41 ± 1.02 and 100.05 ± 0.89 for DAPand FLX, respectively, the developed method was successfully applied to analysis of DAP and FLX in bulk powder, laboratory-prepared mixtures containing different percentages of degradation products and pharmaceutical dosage forms.

UPLC method was also directed to investigate the degradation kinetic processes of both drugs. It was followed pseudo-first order reactions with a degradation reaction rate constant (k) of 0.0575 (h-1) and 0.965 (h-1) and half-life (t1/2) of 12.04 and 0.75 (h) for DAP and FLX, respectively. The degradation rate (k) obeyed Arrhenius equation and the activation energies were calculated. The degradation products (I-III) were separated by UPLC and subjected to MS spectrometry to confirm their structures and elucidate degradation pathway. The developed methods were validated as per ICH guidelines.