The influence of pH and temperature on the stability of flutamide. An HPLC investigation and identification of the degradation product by EI+-MS

The chemical stability of flutamide (FLT) was investigated using a new validated stability-indicating HPLC method. Separation of FLT from its degradation product was achieved on a C18 column using a mobile phase of methanol-phosphate buffer (0.04 M, pH 4.0) (75:25, v/v) with UV-detection at 240 nm. The method exhibited excellent linearity for FLT over the concentration range of 0.2-25.0 μg mL-1. FLT was found to be labile to degradation in buffered, acidic and alkaline solutions. The degradation kinetics of FLT in aqueous solutions was evaluated as a function of pH and temperature. Degradation of FLT followed first-order kinetics and Arrhenius behavior over the temperature ranges of 70-100 and 60-90 °C under acidic and alkaline conditions, respectively. The pH-rate profile was studied over the pH range of 2.0-12.0 with a maximum stability at pH 3.0-5.0. The activation energies for hydrolysis of FLT were calculated as 79.4 and 52.0 kJ mol-1 at pH 0.5 (0.3 M HCl) and 12.5 (0.03 M NaOH), respectively. 4-Nitro-3-trifluoromethyl aniline was identified by mass spectrometry to be the degradation product resulting from the hydrolysis of FLT. The proposed HPLC method was validated according to ICH guidelines and applied for the quality control of FLT in commercial tablets with a mean percentage recovery of 100.09 ± 0.20%

Stability Study of the Antihistamine Drug Azelastine HCl along with a Kinetic Investigation and the Identification of New Degradation Products

The first stability-indicating HPLC method was developed and validated for azelastine HCl (AZL). The separation of AZL from its degradation products was achieved on a C18 column using acetonitrile-0.04 M phosphate buffer of pH 3.5 (32:68, v/v) as a mobile phase with UV-detection at 210 nm and naftazone as an internal standard. The method was rectilinear over the range of 0.2 - 20.0 μg mL-1 with a detection limit of 7.05 ng mL-1. The degradation behavior of AZL was studied under different ICH-recommended stress conditions along with a kinetic investigation; also, degradation products were identified by mass spectrometry. The method was applied for the quality control and stability assessment of AZL in eye drops and nasal spray. The obtained results were favorably compared with those obtained by a comparison method