Metronidazole
;)
1H-Imidazole-1-ethanol,2-methyl-5-nitro-.
2-Methyl-5-nitroimidazole-1-ethanol [443-48-1].
»Metronidazole contains not less than 99.0percent and not more than 101.0percent of C6H9N3O3,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed,light-resistant containers.Store at 25
,excursions permitted between 15and 30.
,excursions permitted between 15and 30.
Identification—
A:Infrared Absorption á197Kñ.
Solution:
20µg per mL.
Medium:
sulfuric acid in methanol (1in 350).
Loss on drying á731ñ—
Dry it at 105for 2hours:it loses not more than 0.5%of its weight.
for 2hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ:
not more than 0.1%.
Heavy metals,Method IIá231ñ:
0.005%.
Non-basic substances—
A1-g portion dissolves completely in 10mLof dilute hydrochloric acid (1in 2).
Chromatographic purity—
Dissolve 100mg of Metronidazole in 10.0mLof acetone.Similarly prepare a Standard solution of USP Metronidazole RSin acetone having a concentration of 3.0mg per mL.Dilute an aliquot of this Standard solution quantitatively and stepwise with acetone to obtain a solution having a concentration of 30µg per mL(diluted Standard solution).Apply separately 20-µLportions of the test solution,the Standard solution,and the diluted Standard solution to a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel.Allow the spots to dry,and develop the chromatogram in a solvent system consisting of a mixture of chloroform,dehydrated alcohol,diethylamine,and water (80:10:10:1)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and allow the solvent to evaporate.Spray the plate with titanium trichloride (20%solution),heat at 110until the blue-gray color begins to disappear,and cool the plate.Spray [Caution—Use fast blue Bsalt spray with adequate ventilation,avoid inhalation of vapors,and avoid contact with the skin
]the plate with fast blue Bsalt solution (1in 100),allow to stand for 3minutes,and spray with a mixture of alcohol,water,and ammonium hydroxide (50:30:20):the RFvalue of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution,and no spot,other than the principal spot,obtained from the test solution is larger or more intense than the principal spot obtained from the diluted Standard solution.
until the blue-gray color begins to disappear,and cool the plate.Spray [Caution—Use fast blue Bsalt spray with adequate ventilation,avoid inhalation of vapors,and avoid contact with the skin
]the plate with fast blue Bsalt solution (1in 100),allow to stand for 3minutes,and spray with a mixture of alcohol,water,and ammonium hydroxide (50:30:20):the RFvalue of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution,and no spot,other than the principal spot,obtained from the test solution is larger or more intense than the principal spot obtained from the diluted Standard solution.
Assay—
Dissolve about 100mg of Metronidazole,accurately weighed,in 20mLof acetic anhydride,warming slightly to effect solution.Cool,add 1drop of malachite green TS,and titrate with 0.1Nperchloric acid VSfrom a 10-mLmicroburet to a yellow-green endpoint.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nperchloric acid is equivalent to 17.12mg of C6H9N3O3.
Auxiliary Information—
Staff Liaison:Behnam Davani,Ph.D.,MBA,Senior Scientist
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 1285
Pharmacopeial Forum:Volume No.29(6)Page 1933
Phone Number:1-301-816-8394