Benzalkonium Chloride

Ammonium,alkyldimethyl(phenylmethyl)-,chloride.
Alkylbenzyldimethylammonium chloride [8001-54-5].
»Benzalkonium Chloride is a mixture of alkylbenzyldimethylammonium chlorides of the general formula:
[C6H5CH2N(CH3)2R]Cl
in which Rrepresents a mixture of alkyls,including all or some of the group beginning with n-C8H17and extending through higher homologs,with n-C12H25,n-C14H29,and n-C16H33comprising the major portion.On the anhydrous basis,the content of the n-C12H25homolog is not less than 40.0percent,and the content of the n-C14H29homolog is not less than 20.0percent,of the total alkylbenzyldimethylammonium chloride content.The amounts of the n-C12H25and n-C14H29homolog components comprise together not less than 70.0percent of the total alkylbenzyldimethylammonium chloride content.The total alkylbenzyldimethylammonium chloride content,calculated on the anhydrous basis,allowance being made for the amount of residue on ignition,is not less than 97.0percent and not more than 103.0percent of [C6H5CH2N(CH3)2R]Cl.
Packaging and storage— Preserve in tight containers.
Identification—
A: To a solution (1in 100)add 2Nnitric acid or mercuric chloride TS:a white precipitate is formed,and it is soluble in alcohol.
B: Dissolve about 200mg in 1mLof sulfuric acid,add 100mg of sodium nitrate,and heat on a steam bath for 5minutes.Cool,dilute with water to 10mL,add 500mg of zinc dust,and warm for 5minutes on a steam bath.To 2mLof the clear supernatant add 1mLof sodium nitrite solution (1in 20),cool in ice water,then add 3mLof a solution of 500mg of 2-naphthol in 10mLof 6Nammonium hydroxide:an orange-red color is produced.
C: Asolution of it in a mixture of equal volumes of water and alcohol responds to the tests for Chloride á191ñ.
Water,Method Iá921ñ: not more than 15.0%.
Residue on ignition á281ñ: not more than 2.0%.
Water-insoluble matter— Asolution (1in 10)is free from turbidity and insoluble matter.
Limit of foreign amines— To 5mLof a solution (1in 50)add 3mLof 1Nsodium hydroxide:no precipitate is formed.Heat to boiling:the odor of amines is not perceptible.
Ratio of alkyl components—
Mobile phase— Adjust a 0.1Msolution of sodium acetate with glacial acetic acid to a pHof 5.0.Mix 55parts of this solution with 45parts of acetonitrile,filter,and degas.The acetonitrile concentration may be varied from 40parts to 60parts to meet system suitability requirements.
Standard solution— Dilute USP Benzalkonium Chloride RSwith water to obtain a solution having a known concentration of about 4mg per mL.
Test solution— Dissolve about 1g of Benzalkonium Chloride,accurately weighed,in water in a 50-mLvolumetric flask,dilute with water to volume,and mix.Pipet 5.0mLof this solution into a 25-mLvolumetric flask,dilute with water to volume,and mix.
Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm ×30-cm column that contains packing L10.The flow rate is about 2mLper minute.Chromatograph the Standard solution,and record the peak areas as directed for Procedure:the resolution,R,between the C12and C14peaks is not less than 1.5;the column efficiency,determined from the C12peak,is not less than 1000theoretical plates;and the relative standard deviation for replicate injections is not more than 2.0%determined from the C12peak.
Procedure— Inject about 20µLof the Test solutioninto the chromatograph,record the chromatogram,and measure the peak areas.Identify the homolog peaks by comparison of the retention times with those from the Standard solution,similarly chromatographed.Calculate the percentage of each quaternary ammonium homolog taken by the formula:
100(A/B),
in which Ais the product of the area obtained from the homolog multiplied by its molecular weight;and Bis the sum of all of these products.The molecular weights of the C10,C12,C14,and C16homologs are 312,340,368,and 396,respectively.
Assay for total alkylbenzyldimethylammonium chlorides— Weigh accurately a quantity of Benzalkonium Chloride equivalent to about 500mg of anhydrous benzalkonium chloride,and transfer,with the aid of 35mLof water,to a glass-stoppered,250-mLconical separator containing 25mLof chloroform.Add 10.0mLof freshly prepared potassium iodide solution (1in 20),insert the stopper in the separator,shake,allow the layers to separate,and discard the chloroform layer.Wash the aqueous layer with three 10-mLportions of chloroform,and discard the washings.Transfer the aqueous layer to a glass-stoppered,250-mLconical flask,and rinse the separator with three 5-mLportions of water,adding the washings to the flask.Add 40mLof cold hydrochloric acid to the flask,mix,and titrate with 0.05Mpotassium iodate VSuntil the solution becomes light brown in color.Add 5mLof chloroform,insert the stopper into the flask,and shake vigorously.Continue the titration,dropwise,with shaking after each addition,until the chloroform layer becomes colorless and the aqueous layer is clear yellow.Perform a blank determination,using 20mLof water as the sample.The difference between the two titrations represents the amount of potassium iodate equivalent to the weight of benzalkonium chloride in the sample.Each mLof 0.05Mpotassium iodate is equivalent to x/10mg of benzalkonium chloride,where xrepresents the average molecular weight of the sample,derived by summing,for all homologs,the products
W(A/B),
where Wis the molecular weight of a given homolog,Ais the area of the peak produced by that homolog in the chromatogram from the Ratio of alkyl componentstest,and Bis the total peak area for all homologs in that chromatogram.
Auxiliary Information— Staff Liaison:Daniel K.Bempong,Ph.D.,Scientist
Expert Committee:(EMC)Excipients:Monograph Content
USP28–NF23Page 2964
Pharmacopeial Forum:Volume No.27(4)Page 2789
Phone Number:1-301-816-8143