Econazole nitrate

A sample of distilled base in cold isopropanol is treated with excess methyl iodide, left at room temperature overnight, diluted with 5 volumes of ethyl acetate and filtered from the methiodide salt. This is purified by crystallization from mixtures of isopropanol and ethyl acetate, filtering hot to remove an impurity of low solubility. The pure methiodide is obtained as a white solid, MP 124° to 124.5°C, containing 99 mol percent thiol isomer. 

Patent 2,911,430 November 3,1959 assigned to Campbell Pharmaceuticals, Inc. 

Chemical Name 1- 2-[(4-chlorophenyl)methoxy]-2-(2,4-dichlorophenyl)ethyl -IH-imidazole nitrate 

Trade Name Manufacturer Country Year Introduced 

A suspension of 10.3 parts of a-(2,4-dichlorophenyl)-imidazole-1-ethanol and 2.1 parts of sodium hydride in 50 parts of dry tetrahydrofuran is stirred and refluxed for 2 hours. 

After this reaction-time, the evolution of hydrogen is ceased. Then there are added successively 60 parts dimethylformamide and 8 parts of p-chlorobenzylchloride and stirring and refluxing is continued for another two hours. The tetrahydrofuran is removed at atmospheric pressure. The dimethylformamide solution is poured onto water. The product, 1-[2,4-dichloro-/3-(p-chlorobenzyloxy)phenethyl] imidazole, is extracted with benzene. The extract is washed with water, dried, filtered and evaporated in vacuo. From the residual oily free base, the nitrate salt is prepared in the usual manner in 2-propanol by treatment with concentrated nitric acid, yielding, after recrystallization of the crude solid salt from a mixture of 2-propanol, methanol and diisopropylether, 1-[2,4-dichloro-/3-(p-chlorobenzyl-oxylphenethyl] imidazole nitrate MP 162°C. 

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Reference solution (b). Dissolve 30 mg of miconazole CRS and 30 mg of econazole nitrate CRS in the mobile phase and dilute to 5 mL with the mobile phase. 

Inject 10 pL of reference solution (a). When the chromatograms are recorded in the prescribed conditions, the retention times are econazole nitrate, about 10 min miconazole, about 20 min. The test is not valid unless the resolution between the peaks corresponding to econazole nitrate and miconazole is not less than 10 if necessary, adjust the composition of the mobile phase. 

Related substances. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the gel containing 50 mg of miconazole with 25 mL of methanol for 30 min, add sufficient methanol to produce 50 mL and filter through a glass microfibre (Whatman GF/C is suitable). For solution (2) dilute 1 volume of solution (1) to 100 volumes with methanol and dilute 5 volumes of the resulting solution to 20 volumes with methanol. Solution (3) contains 0.0025% (w/v) of miconazole nitrate BPCRS and econazole nitrate BPCRS in methanol. 

A chromatographic mobile phase consisting of acetonitrile/0.1 M sodium acetate buffer pH 4.0 (70 30) is prepared. Separate stock solutions in 250 ml of chromatographic mobile phase containing miconazole nitrate (200 20 mg) and econazole nitrate (200 20 mg) (internal standard) are prepared. 25 ml of econazole nitrate stock solution is transferred to five 100 ml volumetric flasks and varying amounts of miconazole stock solution 15, 20, 25, 30 and 35 ml are added to the five flasks. The flasks containing the calibration series are diluted to volume with mobile phase. A sample of cream containing 20 mg miconazole nitrate is shaken with 25 ml... 

Imidazoles clotrimazole econazole nitrate ketoconazole miconazole nitrate oxiconazole nitrate tioconazole... 

Imidazoles clotrimazole econazole nitrate metronidazole miconazole nitrate... 

Ellard, S. Parry, E.M. (1993) Induction of micronuclei in V79 Chinese hamster cells by hydroquinone and econazole nitrate. Mutat. Res.. 287, 87-91... 

Econazole nitrate (Spectazole) is administered only topically and comes as a water-miscible cream (1%), which is applied twice a day. 

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