2-(Diphenylmethoxy)-N,N-dimethylethylamine hydrochloride [147-24-0].
»Diphenhydramine Hydrochloride contains not less than 98.0percent and not more than 102.0percent of C17H21NO·HCl,calculated on the dried basis.
Packaging and storage Preserve in tight,light-resistant containers.Store at room temperature.
A: It meets the requirements under IdentificationOrganic Nitrogenous Bases á181ñ.
B: The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.
C: It responds to the tests for Chloride á191ñ.
Melting range á741ñ: between 167and 172.
Loss on drying á731ñ Dry it at 105for 3hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ: not more than 0.1%.
Organic volatile impurities,Method Iá467ñ: meets the requirements.
Mobile phase Prepare a solution of acetonitrile,water,and triethylamine (50:50:0.5),adjust with glacial acetic acid to a pHof 6.5,filter,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation Dissolve an accurately weighed quantity of USP Diphenhydramine Hydrochloride RSin water to obtain a solution having a known concentration of about 0.5mg per mL.
Assay preparation Transfer about 25mg of Diphenhydramine Hydrochloride,accurately weighed,to a 50-mLvolumetric flask,dissolve in and dilute with water to volume,mix,and filter.
System suitability solution Dissolve about 5mg of benzophenone in 5mLof acetonitrile,dilute with water to 100mL,and mix.Transfer 1.0mLof this solution and 5mg of diphenhydramine hydrochloride to a 10-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 4.6-mm ×25-cm column that contains packing L10.The flow rate is about 1mLper minute.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the resolution,R,between the benzophenone and diphenhydramine peaks is not less than 2.0.Chromatograph replicate injections of the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation is not more than 2.0%;and the tailing factor for the diphenhydramine hydrochloride peak is not more than 2.0.
Procedure Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C17H21NO·HCl in the portion of Diphenhydramine Hydrochloride taken by the formula:
50C(rU/rS),in which Cis the concentration,in mg per mL,of USP Diphenhydramine Hydrochloride RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28NF23Page 667Pharmacopeial Forum:Volume No.29(5)Page 1466