Doxepin Hydrochloride Capsules
»Doxepin Hydrochloride Capsules contain not less than 90.0percent and not more than 110.0percent of the labeled amount of doxepin (C19H21NO).
Packaging and storage— Preserve in well-closed containers.
Identification— Transfer the contents of 2Capsules to a suitable flask.Add about 30mLof chloroform,and shake by mechanical means for 30minutes.Dilute with chloroform to 50mL,and mix.Quickly filter a portion of the solution through Whatman No.4filter paper,rejecting the first 15mLof the filtrate.Pipet an aliquot of the filtered solution containing about 10mg of doxepin into a separator.Add,if necessary,additional chloroform to bring the volume to 25mL.Extract with 50mLof 1Nsodium hydroxide,and drain the chloroform into another separator.Discard the sodium hydroxide washing.Wash the chloroform solution with 20mLof 1Nsodium hydroxide.Filter the chloroform layer through cotton into a 100-mLvolumetric flask,extract the aqueous layer with 25mLof chloroform,and add the chloroform layer to the volumetric flask.Dilute with chloroform to volume,and mix.Inject a portion of the chloroform solution,equivalent to 0.5µg of doxepin,diluting the chloroform solution,if necessary,into a gas chromatograph equipped with a flame-ionization detector and a 3.1-m ×2-mm column packed with 3%cyanomethylphenyl silicone liquid phase on 80-to 110-mesh acid-washed,silanized diatomaceous earth.The carrier gas is helium flowing at a rate of 30mLper minute.The column temperature is 220,and the temperature of the injection port and the detector is 250.The retention times obtained for the (Z)-and (E)-isomer peaks in the chromatogram of the solution from the Capsules are the same as those obtained for a 20-mg specimen of USP Doxepin Hydrochloride RStreated and chromatographed in a similar manner.
Dissolution á711ñ—
Medium: water;900mL.
Apparatus 1: 50rpm.
Time: 30minutes.
Procedure— Determine the amount of C19H21NOdissolved from UVabsorbances at the wavelength of maximum absorbance at about 292nm of filtered portions of the solution under test,suitably diluted with Dissolution Medium,if necessary,in comparison with a Standard solution having a known concentration of USP Doxepin Hydrochloride RSin the same medium.
Tolerances— Not less than 80%(Q)of the labeled amount of C19H21NOis dissolved in 30minutes.
Uniformity of dosage units á905ñ: meet the requirements,the following procedure being used where the test for Content Uniformityis required.
Diluting solution— Prepare a mixture containing 500mLof methanol and 500mLof 0.05Mmonobasic sodium phosphate,and filter.Adjust with 2Nsodium hydroxide to a pHof 6.7.
Standard preparation— Transfer 20mg of USP Doxepin Hydrochloride RS,accurately weighed,to a 200-mLvolumetric flask,dissolve in and dilute with Diluting solutionto volume,and filter.
Test preparation— Transfer the contents of 1Capsule into an appropriate volumetric flask,add Diluting solutionto about 80%of the volume of the flask,and shake the flask by mechanical means for about 30minutes.Dilute with Diluting solutionto volume.Make further dilutions,if necessary,to obtain a solution having a known concentration of 0.1mg per mLof doxepin hydrochloride.Individually test 9more Capsules using the above procedure.
Procedure— Determine the amount of active ingredient in each unit of the Test preparationfrom UVabsorbances at the wavelength of maximum absorbance at about 292nm using 0.5-cm cells in comparison with the Standard preparation.
Water,Method Iá921ñ: not more than 9.0%,determined on the contents of 1Capsule.
Assay—
Mobile phase ,Standard preparation,and Chromatographic system—Proceed as directed in the Assayunder Doxepin Hydrochloride.
Assay preparation— Remove,as completely as possible,the contents of not less than 20Capsules.Weigh the contents and determine the average weight per Capsule.Mix the combined contents,and transfer an accurately weighed quantity of the powder,equivalent to about 50mg of doxepin hydrochloride,to a 100-mLvolumetric flask.Add about 70mLof Mobile phase,and shake by mechanical means for 30minutes.Dilute with Mobile phaseto volume,mix,and filter.Pipet 10.0mLof this solution into a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Procedure— Proceed as directed for Procedurein the Assayunder Doxepin Hydrochloride.Calculate the quantity,in mg,of C19H21NO·HCl in the portion of Capsules taken by the formula:
0.5C[(rU(Z)+rU(E))/(rS(Z)+rS(E))],
in which the terms are as defined therein.
Auxiliary Information— Staff Liaison:Salvador C.Salado,M.S.,Scientist and Latin American Liaison
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 694
Phone Number:1-301-816-8165