C8H9NO2 151.16

Acetamide,N-(4-hydroxyphenyl)-.
4¢-Hydroxyacetanilide [103-90-2].

Packaging and storage— Preserve in tight,light-resistant containers,and store at controlled room temperature.

USP Reference standards á11ñ— USP Acetaminophen RS.

Identification—

Melting range á741ñ: between 168and 172.

Water,Method Iá921ñ: not more than 0.5%.

Residue on ignition á281ñ: not more than 0.1%.

Chloride á221ñ— Shake 1.0g with 25mLof water,filter,and add 1mLof 2Nnitric acid and 1mLof silver nitrate TS:the filtrate shows no more chloride than corresponds to 0.20mLof 0.020Nhydrochloric acid (0.014%).

Sulfate á221ñ— Shake 1.0g with 25mLof water,filter,add 2mLof 1Nacetic acid,then add 2mLof barium chloride TS:the mixture shows no more sulfate than corresponds to 0.20mLof 0.020Nsulfuric acid (0.02%).

Sulfide— Place about 2.5g in a 50-mLbeaker.Add 5mLof alcohol and 1mLof 3Nhydrochloric acid.Moisten a piece of lead acetate test paper with water,and fix to the underside of a watch glass.Cover the beaker with the watch glass so that part of the lead acetate paper hangs down near the pouring spout of the beaker.Heat the contents of the beaker on a hot plate just to boiling:no coloration or spotting of the test paper occurs.

Heavy metals,Method IIá231ñ: 0.001%.

Free p-aminophenol— Transfer 5.0g to a 100-mLvolumetric flask,and dissolve in about 75mLof a mixture of equal volumes of methanol and water.Add 5.0mLof alkaline nitroferricyanide solution (prepared by dissolving 1g of sodium nitroferricyanide and 1g of anhydrous sodium carbonate in 100mLof water),dilute with a mixture of equal volumes of methanol and water to volume,mix,and allow to stand for 30minutes.Concomitantly determine the absorbances of this solution and of a freshly prepared solution of p-aminophenol,similarly prepared at a concentration of 2.5µg per mL,using the same quantities of the same reagents,in 1-cm cells,at the maximum at about 710nm,with a suitable spectrophotometer,using 5.0mLof alkaline nitroferricyanide solution diluted with a mixture of equal volumes of methanol and water to 100mLas the blank:the absorbance of the test solution does not exceed that of the standard solution,corresponding to not more than 0.005%of p-aminophenol.

Limit of p-chloroacetanilide— Transfer 1.0g to a glass-stoppered,15-mLcentrifuge tube,add 5.0mLof ether,shake by mechanical means for 30minutes,and centrifuge at 1000rpm for 15minutes or until a clean separation is obtained.Apply 200µLof the supernatant,in 40-µLportions,to obtain a single spot not more than 10mm in diameter to a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Similarly apply 40µLof a Standard solution in ether containing 10µg of p-chloroacetanilide per mL,and allow the spots to dry.Develop the chromatogram in an unsaturated chamber,with a solvent system consisting of a mixture of solvent hexane and acetone (75:25),until the solvent front has moved 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.Locate the spots in the chromatogram by examination under short-wavelength UVlight:any spot obtained from the solution under test,at an RFvalue corresponding to the principal spot from the Standard solution,is not greater in size or intensity than the principal spot obtained from the Standard solution,corresponding to not more than 0.001%of p-chloroacetanilide.

Readily carbonizable substances á271ñ— Dissolve 0.50g in 5mLof sulfuric acid TS:the solution has no more color than Matching Fluid A.

Organic volatile impurities,Method Vá467ñ: meets the requirements.

Assay— Dissolve about 120mg of Acetaminophen,accurately weighed,in 10mLof methanol in a 500-mLvolumetric flask,dilute with water to volume,and mix.Transfer 5.0mLof this solution to a 100-mLvolumetric flask,dilute with water to volume,and mix.Concomitantly determine the absorbances of this solution and of a Standard solution of USP Acetaminophen RS,in the same medium,at a concentration of about 12µg per mLin 1-cm cells,at the wavelength of maximum absorbance at about 244nm,with a suitable spectrophotometer,using water as the blank.Calculate the quantity,in mg,of C8H9NO2in the Acetaminophen taken by the formula: in which Cis the concentration,in µg per mL,of USP Acetaminophen RSin the Standard solution;and AUand ASare the absorbances of the solution of Acetaminophen and the Standard solution,respectively.

Expert Committee:(PA2)Pharmaceutical Analysis 2

USP28–NF23Page 16

Phone Number:1-301-816-8139