Perphenazine and Amitriptyline Hydrochloride Tablets, chemical structure, molecular formula, Reference Standards

Perphenazine and Amitriptyline Hydrochloride Tablets

»Perphenazine and Amitriptyline Hydrochloride Tablets contain not less than 90.0percent and not more than 110.0percent of the labeled amounts of perphenazine (C21H26ClN3OS)and amitriptyline hydrochloride (C20H23N·HCl).

Packaging and storage— Preserve in well-closed containers.

USP Reference standards á11ñ— USP Amitriptyline Hydrochloride RS.USP Perphenazine RS.

NOTE—Throughout the following procedures,protect test or assay specimens,the USP Reference Standard,and solutions containing them,by conducting the procedures without delay,under subdued light,or using low-actinic glassware.

Identification— Transfer a portion of powdered Tablets,equivalent to about 40mg of perphenazine,to a 100-mLvolumetric flask containing about 50mLof alcohol.Agitate for 20minutes,add alcohol to volume,mix,and filter or centrifuge.Separately prepare two Standard solutions containing 0.4mg per mLof USP Perphenazine RSand USP Amitriptyline Hydrochloride RS,respectively,in alcohol.Separately apply 5µLof the test solution and 5µLof each Standard solution to a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Develop the chromatogram using a solvent system consisting of a mixture of cyclohexane,ethyl acetate,and diethylamine (85:25:5)until the solvent front has moved about 15cm.Remove the plate from the developing chamber,air-dry for 20minutes,and examine the plate under short-wavelength UVlight:the RFvalues of the principal spots obtained from the test solution correspond to those obtained from the Standard solutions.

Dissolution á711ñ—

Medium: 0.1Nhydrochloric acid;900mL.

Apparatus 2: 50rpm.

Time: 60minutes.

Procedure— [NOTE—Due to potential decrease in the recovery of perphenazine when multiple injections are made from a vial,no more than two withdrawals should be made from any single vial.]Determine the amounts of perphenazine and amitriptyline hydrochloride in solution in filtered portions of the solution under test,in comparison with a Standard solution having known concentrations of USP Perphenazine RSand USP Amitriptyline Hydrochloride RSin the same medium,as directed for Procedurein the Assay.

Tolerances— Not less than 75%(Q)of the labeled amounts of perphenazine (C21H26ClN3OS)and amitriptyline hydrochloride (C20H23N·HCl)is dissolved in 60minutes.

Uniformity of dosage units á905ñ: meet the requirements for Content uniformitywith respect to perphenazine and to amitriptyline hydrochloride.

Assay—

Mobile phase— Prepare a filtered and degassed mixture of water,acetonitrile,methanol,and methanesulfonic acid (490:310:200:2).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Standard preparation— Dissolve an accurately weighed quantity of USP Perphenazine RSin methanol,and dilute quantitatively with methanol to obtain a solution having a known concentration of about 0.8mg per mL(Solution P).Transfer 4Jmg of USP Amitriptyline Hydrochloride RSto a 50-mLvolumetric flask,Jbeing the ratio of the labeled amount,in mg,of amitriptyline hydrochloride to the labeled amount,in mg,of perphenazine per Tablet.Add 5.0mLof Solution Pand 20mLof 0.2Nacetic acid,shake,and sonicate to dissolve the USP Reference Standards.Dilute with methanol to volume,and mix.Pipet 25mLof this solution into a 100-mLvolumetric flask,dilute with a mixture of methanol and 0.04Nacetic acid (3:2)to volume,and mix to obtain a Standard preparationhaving known concentrations of about 20µg of USP Perphenazine RSper mLand about 20Jµg of USP Amitriptyline Hydrochloride RSper mL.

Assay preparation— Transfer 10Tablets to a 250-mLvolumetric flask,add 100mLof 0.2Nacetic acid,and shake the mixture until the Tablets have disintegrated.Add methanol to volume,mix,and filter.Dilute an accurately measured volume (VFmL)of the clear filtrate quantitatively with a mixture of methanol and 0.04Nacetic acid (3:2)to obtain a solution (VAmL)containing about 20µg of perphenazine per mL,and filter through a membrane filter.

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 L1.The flow rate is about 1mLper minute,and is adjusted until the relative retention times for perphenazine and amitriptyline are about 1and 1.5,respectively.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation is not more than 2.0%for replicate injections,and the resolution,R,between perphenazine and amitriptyline is not less than 4.

Procedure— Separately inject equal volumes (about 20µL)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 perphenazine (C21H26ClN3OS)in each Tablet taken by the formula:

0.25(C/10)(VA/VF)(rU/rS),

in which Cis the concentration,in µg per mL,of USP Perphenazine RSin the Standard preparation,VAis the volume,in mL,of the Assay preparation,VFis the volume,in mL,of the filtrate taken for the Assay preparation,and rUand rSare the responses of the perphenazine peaks obtained from the Assay preparationand the Standard preparation,respectively.Calculate the quantity,in mg,of amitriptyline hydrochloride (C20H23N·HCl)taken by the same formula,reading amitriptyline hydrochloride instead of perphenazine.

Auxiliary Information— Staff Liaison:Salvador C.Salado,M.S.,Scientist and Latin American Liaison

Expert Committee:(PA3)Pharmaceutical Analysis 3

USP28–NF23Page 1522

Phone Number:1-301-816-8165