C7H4ClNO2 169.56

2(3H)-Benzoxazolone,5-chloro-.
5-Chloro-2-benzoxazolinone [95-25-0].

Packaging and storage— Preserve in tight containers.

USP Reference standards á11ñ— USP Chlorzoxazone RS.USP Chlorzoxazone Related Compound A RS.

Identification—

Melting range á741ñ: between 189and 194.

Loss on drying á731ñ— Dry it at 105for 2hours:it loses not more than 0.5%of its weight.

Heavy metals,Method IIá231ñ: 0.002%.

Residue on ignition á281ñ: not more than 0.15%.

Chromatographic purity— Prepare a Test solutionin methanol containing 20mg per mL.Dissolve a suitable quantity of USP Chlorzoxazone Related Compound A RS(2-Amino-4-chlorophenol)in methanol to obtain a solution containing 100µg per mL(Standard solution A).Dissolve a suitable quantity of p-chlorophenol in methanol to obtain a solution containing 50µg per mL(Standard solution B).Apply separate 10µLportions of the three solutions to the starting line of 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 hexane and dioxane (63:37)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.Locate the spots on the plate by examination under short-wavelength UVlight:any spot obtained from the Test solution,other than one corresponding to chlorzoxazone,does not exceed,in size or intensity,the principal spot obtained from Standard solution A,corresponding to not more than 0.5%of any individual impurity.Expose the plate to iodine vapors in a closed chamber,and locate the spots:any spot obtained from the Test solution,other than one corresponding to chlorzoxazone,does not exceed,in size or intensity,the principal spot obtained from Standard solution B,corresponding to not more than 0.25%of any individual impurity.

Organic volatile impurities,Method Vá467ñ: meets the requirements.

Chlorine content— Dissolve about 300mg,accurately weighed,in 10mLof alcohol in a suitable flask.Add 3.5g of Raney's nickel-aluminum catalyst,and connect to a suitable reflux condenser.Chill the flask in an ice bath,and add through the condenser 75mLof 2.5Nsodium hydroxide.When the reaction has subsided,remove the ice bath.After 10minutes,heat the flask gently,gradually increasing the heat until the mixture refluxes rapidly.After 90minutes from the time of the addition of the alkali,discontinue heating,cool,and rinse the condenser with water,collecting the rinsings in the flask.Transfer the liquid to a 200-mLvolumetric flask,wash the residue with water,and add the washing to the volumetric flask.Dilute with water to volume,and mix.Transfer 100.0mLof this solution to a beaker,neutralize,then acidify (using congo red as the indicator)by adding nitric acid dropwise with mixing.Titrate with 0.1Nsilver nitrate VS,determining the endpoint potentiometrically,using silver and calomel electrodes.Each mLof 0.1Nsilver nitrate is equivalent to 3.545mg of Cl:the content of Cl,calculated on the dried basis,is between 20.6%and 21.2%.

Assay— Transfer about 50mg of Chlorzoxazone,accurately weighed,to a 100-mLvolumetric flask.Dissolve in methanol,dilute with methanol to volume,and mix.Transfer 4.0mLof this solution to a 100-mLvolumetric flask,dilute with methanol to volume,and mix.Concomitantly determine the absorbances of this solution and a Standard solution of USP Chlorzoxazone RSin methanol at a concentration of about 20µg per mLin 1-cm cells at the wavelength of maximum absorbance at about 282nm,with a suitable spectrophotometer,using methanol as the blank.Calculate the quantity,in mg,of C7H4ClNO2in the Chlorzoxazone taken by the formula: in which Cis the concentration,in µg per mL,of USP Chlorzoxazone RSin the Standard solution,and AUand ASare the absorbances of the solution of Chlorzoxazone and the Standard solution,respectively.

Expert Committee:(PA3)Pharmaceutical Analysis 3

USP28–NF23Page 462

Phone Number:1-301-816-8165