»Chloroxylenol contains not less than 98.5percent of C8H9ClO.
Packaging and storage Preserve in well-closed containers.
Melting range á741ñ: between 114and 116.
Water,Method Iá921ñ: not more than 0.5%.
Residue on ignition á281ñ: not more than 0.1%.
Iron á241ñ Transfer 0.10g to a suitable crucible,add 5drops of sulfuric acid,and ignite at a low heat until thoroughly ashed.Add to the carbonized mass 10drops of sulfuric acid,and heat cautiously until white fumes are no longer evolved.Ignite,preferably in a muffle furnace,at 500to 600,until the carbon is completely burned off.Cool,add 4mLof 6Nhydrochloric acid,cover,digest on a steam bath for 15minutes,uncover,and slowly evaporate on a steam bath to dryness.Moisten the residue with 1drop of hydrochloric acid,add 10mLof hot water,and digest for 2minutes.Dilute with water to about 25mL.Filter,if necessary,rinse the crucible and the filter with 10mLof water,combining the filtrate and rinsing in a 50-mLcolor-comparison tube,add 2mLof hydrochloric acid,dilute with water to 47mL,and mix.The limit is 0.01%.
Standard solution Quantitatively dissolve accurately weighed quantities of 3,5-dimethylphenol and USP Chloroxylenol Related Compound A RSin chloroform to obtain a solution containing about 0.08mg of each per mL.
Test solution Quantitatively dissolve an accurately weighed quantity of Chloroxylenol in chloroform to obtain a solution containing about 40.0mg per mL.
Chromatographic system(see Chromatography á621ñ) The gas chromatograph is equipped with a flame-ionization detector and a 4-mm ×1.8-m column packed with 3%phase G16on support S1A.The carrier gas is dry nitrogen,flowing at a rate of about 30mLper minute.The column temperature is maintained at 180,and the injection port and detector block temperatures are maintained at 200.Chromatograph theStandard solution,and record the peak responses as directed forProcedure:the resolution,R,between 3,5-dimethylphenol and chloroxylenol related compound Ais not less than 4.5;and the relative standard deviation for replicate injections is not more than 10%.
Procedure Separately inject equal volumes (about 1µL)of theStandard solutionand theTest solutioninto the chromatograph,record the chromatograms,and measure the areas for all the peaks.Calculate the percentages of 3,5-dimethylphenol (C8H10O)and chloroxylenol related compound A(C8H9ClO)in the portion of Chloroxylenol taken by the formula:
0.2(rU/rS),in whichrUandrSare the peak areas of the appropriate analyte obtained from theTest solutionand theStandard solution,respectively:not more than 0.2%of 3,5-dimethylphenol or chloroxylenol related compound Ais found.Calculate the percentage of each impurity in the portion of Chloroxylenol taken by the formula:
100(ri/rs),in whichriis the area of each peak obtained from theTest solution,excluding that of the main chloroxylenol peak,the 3,5-dimethylphenol peak,and the chloroxylenol related compound Apeak;andrsis the sum of the areas of all the peaks:not more than 0.5%of any individual impurity is found.Calculate the percentage of total impurities in the portion of Chloroxylenol taken by the formula:
100(rT/rs),in whichrTis the sum of the areas of all the peaks obtained from theTest solution,excluding that of the main chloroxylenol peak;andrsis the sum of the areas of all the peaks obtained from theTest solution:not more than 1.5%of total impurities is found.
Internal standard solution Prepare a solution ofp-chlorophenol in chloroform containing about 0.8mg per mL.
Standard preparation Dissolve an accurately weighed quantity of USP Chloroxylenol RSinInternal standard solutionto obtain a solution having a known concentration of about 1mg per mL.
Assay preparation Transfer about 100mg of Chloroxylenol,accurately weighed,to a 100-mLvolumetric flask,dissolve inInternal standard solution,dilute withInternal standard solutionto volume,and mix.
Chromatographic system(see Chromatography á621ñ) The gas chromatograph is equipped with a flame-ionization detector and a 4-mm ×1.8-m column packed with 3%phase G16on support S1A.The injection port,column,and detector block are maintained at 210.Dry nitrogen,flowing at a rate of about 30mLper minute,is used as the carrier gas.Chromatograph theStandard preparation,and record the peak responses as directed forProcedure:the resolution,R,between thep-chlorophenol peak and the chloroxylenol peak is not less the 2.0;the tailing factor for the chloroxylenol peak is not more than 1.5;and the relative standard deviation for replicate injections is not more than 1.5%.
Procedure [NOTEUse peak areas where peak responses are indicated.]Separately inject equal volumes (about 2µL)of theStandard preparationand theAssay preparationinto the gas chromatograph,record the chromatograms,and measure the responses of the major peaks.Calculate the quantity,in mg,of chloroxylenol (C8H9ClO)in the portion of Chloroxylenol taken by the formula:
100C(RU/RS),in whichCis the concentration,in mg per mL,of USP Chloroxylenol RSin theStandard preparation;andRUandRSare the ratios of the response of the chloroxylenol peak to that of thep-chlorophenol peak obtained from theAssay preparationand theStandard preparation,respectively.
Auxiliary Information Staff Liaison:Behnam Davani,Ph.D.,MBA,Senior Scientist
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28NF23Page 447Pharmacopeial Forum:Volume No.27(6)Page 3264