Benzoic and Salicylic Acids Ointment
»Benzoic and Salicylic Acids Ointment is Benzoic Acid and Salicylic Acid,present in a ratio of about 2to 1,in a suitable ointment base.It contains not less than 90.0percent and not more than 110.0percent of the labeled amounts of benzoic acid (C7H6O2)and salicylic acid (C7H6O3).
Packaging and storage— Preserve in well-closed containers,and avoid exposure to temperatures exceeding 30.
Labeling— Label Ointment to indicate the concentrations of Benzoic Acid and Salicylic Acid and to indicate whether the ointment base is water-soluble or water-insoluble.
Identification— Dissolve an amount of Ointment,equivalent to about 60mg of benzoic acid and 30mg of salicylic acid,in 25mLof a solvent consisting of equal volumes of chloroform and methanol.Prepare separate Standard solutions in the same solvent containing,respectively,2.4mg of USP Benzoic Acid RSin each mLand 1.2mg of USP Salicylic Acid RSin each mL.Apply 5µLof each solution at separate points 2.5cm from the bottom edge of a 20-×20-cm thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture,and allow the spots to dry.Develop the chromatogram in a solvent system consisting of a mixture of chloroform,acetone,isopropyl alcohol,methanol,and ammonium hydroxide (30:30:15:15:10)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the chromatographic chamber,mark the solvent front,and allow the solvent to evaporate.View the chromatogram under short-wavelength (254nm)UVradiation:the two major fluorescent spots from the test solution correspond in color and in RFvalue to those from the respective Standard solutions.
Minimum fill á755ñ: meets the requirements.
Assay—
Ferric chloride-urea reagent— On the day of use,dissolve,without heating,18g of urea in a mixture of 2.5mLof ferric chloride solution (6in 10)and 12.5mLof 0.05Nhydrochloric acid.
Column A— Insert a small pledget of glass wool above the stem constriction of a 20-×2.5-cm chromatographic tube.Mix 1g of chromatographic siliceous earth with 0.5mLof dilute phosphoric acid (3in 10)to form a uniform,fluffy mixture,transfer to the chromatographic tube,and pack evenly over the glass wool,exerting gentle pressure.Similarly,mix 4g of chromatographic siliceous earth with 3mLof Ferric chloride-urea reagent,and pack uniformly over the first layer.Cover the column with a pad of glass wool.
Column B— Insert a small pledget of glass wool above the stem constriction of a second 20-×2.5-cm chromatographic tube.Mix 4g of chromatographic siliceous earth with 2mLof sodium bicarbonate solution (1in 12),prepared just prior to use,to a uniform,fluffy mixture,and pack evenly over the glass wool.Cover the column with a pad of glass wool.
Assay preparation— Transfer an accurately weighed amount of Ointment,equivalent to about 100mg of benzoic acid and 50mg of salicylic acid,to a 250-mLvolumetric flask,and dissolve in about 150mLof chloroform by warming on a steam bath.Cool,dilute with chloroform to volume,and mix.
Procedure— Mount Column Adirectly over Column B,then pipet 10mLof Assay preparationonto Column A,and allow it to pass into the column.Wash the columns with two 40-mLportions of chloroform,allowing the first portion to recede to the top of each column before adding the second portion.Discard the eluates,and separate the columns.
Salicylic acid content— Elute Column Awith 95mLof a 3in 100solution of glacial acetic acid in chloroform,collecting the eluate in a 100-mLvolumetric flask.Dilute the contents of the flask with the same solvent to volume,and mix.Dissolve an accurately weighed quantity of USP Salicylic Acid RSin the same solvent,and dilute quantitatively and stepwise with this solvent to obtain a Standard solution having a known concentration of about 20µg per mL.Concomitantly determine the absorbances of both solutions in 1-cm cells at the wavelength of maximum absorbance at about 311nm,with a suitable spectrophotometer,using a 3in 100solution of glacial acetic acid in chloroform as the blank.Calculate the quantity,in mg,of salicylic acid (C7H6O3)in the portion of Ointment taken by the formula:
2.5C(AU/AS),
in which Cis the concentration,in µg per mL,of USP Salicylic Acid RSin the Standard solution;and AUand ASare the absorbances of the diluted eluate from Column Aand the Standard solution,respectively.
Benzoic acid content— Elute Column Bwith 95mLof a 3in 100solution of glacial acetic acid in chloroform,collecting the eluate in a 100-mLvolumetric flask.Dilute the contents of the flask with the same solvent to volume,and mix.Dissolve an accurately weighed quantity of USP Benzoic Acid RSin the same solvent,and dilute quantitatively and stepwise with this solvent to obtain a Standard solution having a known concentration of about 40µg per mL.Concomitantly determine the absorbances of both solutions in 1-cm cells at the wavelength of maximum absorbance at about 275nm,with a suitable spectrophotometer,using a 3in 100solution of glacial acetic acid in chloroform as the blank.Calculate the quantity,in mg,of benzoic acid (C7H6O2)in the portion of Ointment taken by the formula:
2.5C(AU/AS),
in which Cis the concentration,in µg per mL,of USP Benzoic Acid RSin the Standard solution;and AUand ASare the absorbances of the diluted eluate from Column Band the Standard solution,respectively.
Auxiliary Information— Staff Liaison:Behnam Davani,Ph.D.,MBA,Senior Scientist
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 233
Phone Number:1-301-816-8394