393-11-3Relevant articles and documents
The influence of pH and temperature on the stability of flutamide. An HPLC investigation and identification of the degradation product by EI+-MS
El-Shaheny,Yamada
, p. 3206 - 3214 (2015)
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%. This journal is
Two different spectrophotometric determinations of potential anticancer drug and its toxic metabolite
Farid, Nehal F.,Abdelwahab, Nada S.
, p. 360 - 367 (2015)
Flutamide is a hormone therapy used for men with advanced prostate cancer. Flutamide is highly susceptible to hydrolysis with the production of 3-(trifluoromethyl)aniline, which is reported to be one of its toxic metabolites, impurities and related substances according to BP and USP. Flutamide was found to be stable when exposed to oxidation by 30% hydrogen peroxide and direct sunlight for up to 4 h. Two accurate and sensitive spectrophotometric methods were used for determination of flutamide in bulk and in pharmaceutical formulations. Method (I) is the area under curve (AUC) spectrophotometric method that depends on measuring the AUC in the wavelength ranges of 275-305 nm and 350-380 nm and using Cramer's rule. The linearity range was found to be 1-35 μg/mL and 0.5-16 μg/mL for the drug and the degradate, respectively. In method (II), combination of the isoabsorptive and dual wavelength spectrophotometric methods was used for resolving the binary mixture. The absorbance at 249.2 nm (λiso) was used for determination of total mixture concentration, while the difference in absorbance between 232 nm and 341.2 nm was used for measuring the drug concentration. By subtraction, the degradate concentration was obtained. Beer's law was obeyed in the range of 2-35 μg/mL and 0.5-20 μg/mL for the drug and its degradate, respectively. The two methods were validated according to USP guidelines and were applied for determination of the drug in its pharmaceutical dosage form. Moreover AUC method was used for the kinetic study of the hydrolytic degradation of flutamide. The kinetic degradation of flutamide was found to follow pseudo-first order kinetics and is pH and temperature dependent. Activation energy, kinetic rate constants and t1/2 at different temperatures and pH values were calculated.
Catalytic reduction of ortho - And para -azidonitrobenzenes via tert -butoxide ion mediated electron transfer
Burnley, James,Carbone, Giorgio,Moses, John E.
supporting information, p. 652 - 656 (2013/04/10)
The reduction of a range of substituted azidonitrobenzene derivatives to the corresponding aniline is described. The chemoselective reaction proceeds cleanly and in good yield, generating minimal waste products. The process involves a thiazolium salt derived species which is proposed as a radical anion relay, with tert-butoxide as the stoichiometric reductant.
