Mebendazole Tablets
»Mebendazole Tablets contain not less than 90.0percent and not more than 110.0percent of the labeled amount of mebendazole (C16H13N3O3).
Packaging and storage— Preserve in well-closed containers.
Identification— Finely powder a quantity of Tablets,equivalent to about 200mg of mebendazole,and mix the powder with 20mLof a mixture of chloroform and 96percent formic acid (19:1).Warm the suspension on a water bath for a few minutes,cool,and filter through a medium-porosity,sintered-glass filter.Apply 10µLof this solution and 10µLof a Standard solution of USP Mebendazole RSin a mixture of chloroform and 96percent formic acid (19:1)containing 10mg per mLto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Allow the spots to dry,and develop the chromatogram in a solvent system consisting of a mixture of chloroform,methanol,and 96percent formic acid (90:5:5)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,allow the solvent to evaporate,and examine the plate under short-wavelength UVlight:the RFvalue of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.
Dissolution á711ñ—
Medium: 0.1Nhydrochloric acid containing 1.0%sodium lauryl sulfate;900mL.
Apparatus 2: 75rpm.
Time: 120minutes.
Determine the amount of C16H13N3O3dissolved by employing the following method.
Buffer solution— Dissolve 8.0g of sodium hydroxide in 2Lof water,add 3.0g of sodium lauryl sulfate,and mix;then add 20mLof phosphoric acid,and adjust with phosphoric acid to a pHof 2.5.
Mobile phase— Prepare a filtered and degassed mixture of acetonitrile and Buffer solution(3:7).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard solution— Transfer 25mg of USP Mebendazole RSto a 50-mLvolumetric flask,add 10.0mLof formic acid and dissolve,dilute with methanol to volume,and mix.Dilute a portion of this solution quantitatively and stepwise with Dissolution Mediumto obtain a solution having a known concentration similar to the expected concentration in the solution under test.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm ×3-cm column that contains packing L7.The flow rate is about 1mLper minute.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 10µL)of filtered portions of the Standard solutionand the solution under test into the chromatograph,record the chromatograms,and measure the responses for the major peaks.
Tolerances— Not less than 75%(Q)of the labeled amount of C16H13N3O3is dissolved in 120minutes.
Uniformity of dosage units á905ñ: meet the requirements.
PROCEDURE FOR CONTENT UNIFORMITY—
Standard preparation— Transfer about 20mg of USP Mebendazole RS,accurately weighed,to a 10-mLvolumetric flask,add 4mLof 96percent formic acid,and mix to dissolve.Add isopropyl alcohol to volume,and mix.Pipet 0.5mLof this solution into a 100-mLvolumetric flask,dilute with isopropyl alcohol to volume,and mix.
Test preparation— Mix 1Tablet with 20mLof 96percent formic acid in a 100-mLvolumetric flask,and heat on a steam bath for 15minutes.Cool,add isopropyl alcohol to volume,mix,and pass through a medium-porosity,sintered-glass filter.Transfer an accurately measured portion of the filtrate,equivalent to 1mg of mebendazole,to a 100-mLvolumetric flask,dilute with isopropyl alcohol to volume,and mix.
Procedure— Concomitantly determine the absorbances of the Standard preparationand the Test preparationin 1-cm cells at the wavelength of maximum absorbance at about 310nm,with a suitable spectrophotometer,using a 1in 500solution of 96percent formic acid in isopropyl alcohol as the blank.Calculate the quantity,in mg,of C16H13N3O3in the Tablet taken by the formula:
(TC/D)(AU/AS),
in which Tis the labeled quantity,in mg,of mebendazole in the Tablet;Cis the concentration,in µg per mL,of USP Mebendazole RSin the Standard preparation;Dis the concentration,in µg per mL,of mebendazole in the Test preparation,based upon the labeled quantity per Tablet and the extent of dilution;and AUand ASare the absorbances of the solutions from the Test preparationand the Standard preparation,respectively.
Assay—
Mobile phase— Prepare a mixture of methanol and 0.05Mmonobasic potassium phosphate (60:40),adjust with 0.1Mphosphoric acid or 1Nsodium hydroxide to a pHof 5.5,filter,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Transfer about 25mg of USP Mebendazole RS,accurately weighed,to a 100-mLvolumetric flask.Add 10mLof formic acid,and heat in a water bath at 50for 15minutes.Shake by mechanical means for 5minutes,add 90mLof methanol,and allow to cool.Dilute with methanol to volume,and mix.Transfer 5.0mLof this solution to a 25-mLvolumetric flask,dilute with Mobile phaseto volume,mix,and filter through a filter having a porosity of 0.5µm or finer.
Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 500mg of mebendazole,to a 100-mLvolumetric flask.Add 50mLof formic acid,and heat in a water bath at 50for 15minutes.Shake by mechanical means for 1hour,dilute with water to volume,mix,and filter.Transfer 5.0mLof the filtrate to a 100-mLvolumetric flask,dilute with a solution of formic acid in methanol (1:9)to volume,and mix.Transfer 5.0mLof this solution to a 25-mLvolumetric flask,dilute with Mobile phaseto volume,mix,and pass through a pass having a porosity of 0.5µm or finer.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 247-nm detector,a precolumn that contains packing L1,and a 3.9-mm ×30-cm analytical column that contains packing L1and is maintained at about 30.The flow rate is about 1.5mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the tailing factor is not more than 2.0,the column efficiency is not less than 2500theoretical plates,and the relative standard deviation for replicate injections is not more than 1%.
Procedure— Separately inject equal volumes (about 15µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of mebendazole (C16H13N3O3)in the portion of Tablets taken by the formula:
10,000C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Mebendazole RSin the Standard preparation;and rUand rSare the mebendazole peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Behnam Davani,Ph.D.,MBA,Senior Scientist
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 1189
Phone Number:1-301-816-8394