393-11-3Relevant academic research and scientific papers
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
The photochemistry of flutamide and its inclusion complex with β-cyclodextrin. Dramatic effect of the microenvironment on the nature and on the efficiency of the photodegradation pathways
Sortino,Giuffrida,De Guidi,Chillemi,Petralia,Marconi,Condorelli,Sciuto
, p. 6 - 13 (2001)
The photochemistry of the anticancer drug flutamide (FM), 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide, in homogeneous media and in the β-cyclodextrin (β-CD) cavity has been investigated. The photoreactivity of the free molecule has been rationalized on the basis of an intramolecular nitro to nitrite rearrangement followed by cleavage of the nitrite intermediate. The twisted geometry of the nitro group with respect to the aromatic plane plays a key role in triggering such a photoprocess. Incorporation of FM in the β-CD cavity leads to dramatic effects on both the efficiency and the nature of the photochemical deactivation pathways of the guest molecule. A 20-fold increase in the FM photodecomposition quantum yield and the formation of photoproducts originated by both reduction of the nitro group and cleavage of the amide bond were observed in the presence of the macrocycle. Such a behavior cannot be attributed exclusively to the micropolarity of β-CD and/or to its role as a reactant. The induced circular dichroism spectra and the nature of the photoproducts formed in these experimental conditions provide indications that the photoreacrivity in the β-CD microenvironment could likely be mediated by structural changes of FM upon complexation.
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.
Structural elucidation of major selective androgen receptor modulator (SARM) metabolites for doping control
Garg, Neeraj,Hansson, Annelie,Knych, Heather K.,Stanley, Scott D.,Thevis, Mario,Bondesson, Ulf,Hedeland, Mikael,Globisch, Daniel
supporting information, p. 698 - 702 (2018/02/09)
Selective androgen receptor modulators (SARMs) are a class of androgen receptor drugs, which have a high potential to be performance enhancers in human and animal sports. Arylpropionamides are one of the major SARM classes and get rapidly metabolized significantly complicating simple detection of misconduct in blood or urine sample analysis. Specific drug-derived metabolites are required as references due to a short half-life of the parent compound but are generally lacking. The difficulty in metabolism studies is the determination of the correct regio and stereoselectivity during metabolic conversion processes. In this study, we have elucidated and verified the chemical structure of two major equine arylpropionamide-based SARM metabolites using a combination of chemical synthesis and liquid chromatography-mass spectrometry (LC-MS) analysis. These synthesized SARM-derived metabolites can readily be utilized as reference standards for routine mass spectrometry-based doping control analysis of at least three commonly used performance-enhancing drugs to unambigously identify misconduct.
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.
Microbial Metabolism. Part 11.1) metabolites of flutamide
Herath, Wimal,Khan, Ikhlas Ahmad
experimental part, p. 562 - 564 (2010/08/20)
The yeast culture, Rhodotorula mucilaginosa (ATCC 20129) transformed flutamide (1) to three metabolites: 4-nitro-3-(trifluoromethyl)aniline (2), 2-methyl-N-[4-amino-3-(trifloromethyl)phenyl]propanamide (3) and N-[4- amino-3-(trifluoromethyl)phenyl]acetami
Light-controlled nitric oxide generation from a novel self-assembled monolayer on a gold surface
Sortino, Salvatore,Petralia, Salvatore,Compagnini, Giuseppe,Conoci, Sabrina,Condorelli, Giuseppe
, p. 1914 - 1917 (2007/10/03)
Quantitative release of NO is exclusively controlled by light excitation in a self-assembled monolayer of an NO donor on a gold surface (see picture). The low excitation energy required, the absence of noxious side effects, the thermal stability under physiological conditions, and the ease of preparation are additional advantages offered by the monolayer-modified gold plate.
Nitroarylamines via the Vicarious Nucleophilic Substitution of Hydrogen: Amination, Alkylamination, and Arylamination of Nitroarenes with Sulfenamides
Makosza, Mieczyslaw,Bialecki, Maciej
, p. 4878 - 4888 (2007/10/03)
A new reaction of sulfenamides with electrophilic arenes under basic conditions is described. The σ adducts formed from nitroarenes and the anions of sulfenamides undergo elimination of thiol to produce the corresponding o- and/or p-nitroanilines. This reaction is analogous to the known alkylation and hydroxylation of nitroarenes via the vicarious nucleophilic substitution of hydrogen (VNS). The reaction gives access to a wide range of substituted nitroanilines, nitronaphthylamines, and aminoheterocycles. By means of the reaction with N-alkyl- and N-arylsulfenamides, it is possible to obtain N-alkylnitroanilines and nitrodiarylamines. By varying the structure of sulfenamide and the reaction conditions, particularly the nature and concentration of the base, it is possible to control the orientation of animation.
Process for the preparation of aromatic amines
-
, (2008/06/13)
Electrophilic aromatic compounds can be reacted with sulphenamides in the presence of bases to form the corresponding aromatic amines.
Amination of Nitroarenes with Sulfenamides via Vicarious Nucleophilic Substitution of Hydrogen
Makosza, Mieczyslaw,Bialecki, Maciej
, p. 4784 - 4785 (2007/10/02)
Nitroarenes react with sulfenamides RSNH2 in the presence of strong bases to give p- and o-nitroanilines.
