Doxepin Hydrochloride Oral Solution
»Doxepin Hydrochloride Oral Solution contains not less than 90.0percent and not more than 110.0percent of the labeled amount of doxepin (C19H21NO).
Packaging and storage— Preserve in tight,light-resistant containers.
Labeling— Label it to indicate that each dose is to be diluted with water or other suitable fluid to approximately 120mL,just prior to administration.
Identification—
Mobile phase— Add 0.2mLof diethylamine to a solution containing 250mLof chloroform and 750mLof acetonitrile in a vacuum flask.Prior to use,degas the contents of the flask by stirring vigorously with a magnetic stirrer,while applying vacuum,for 10minutes.
Procedure— Transfer 5.0mLof the Oral Solution to a 60-mLseparator,add 1mLof sodium hydroxide solution (1in 25),1g of sodium chloride,and 5.0mLof ethyl acetate,and shake the mixture vigorously for 1minute.Allow the phases to separate,transfer 1.0mLof the clear upper phase to a 25-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.Transfer about 22mg of USP Doxepin Hydrochloride RSto a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.Inject 4-µLportions of both solutions into a high-pressure liquid chromatograph (see Chromatography á621ñ)fitted with a 50-cm ×2-mm column packed with silica microspheres and equipped with an UVdetector capable of monitoring absorption at 254nm and a suitable recorder.Adjust the operating parameters to obtain a flow rate of about 24mLper hour.The chromatogram of the test solution exhibits two peaks having retention times that are identical with those obtained with the Standard solution.
Uniformity of dosage units á905ñ—
FOR ORAL SOLUTION PACKAGED IN SINGLE-UNIT CONTAINERS:
meets the requirements.
Deliverable volume á698ñ—
FOR ORAL SOLUTION PACKAGED IN MULTIPLE-UNIT CONTAINERS: meets the requirements.
pHá791ñ: between 4.0and 7.0,the test specimen being allowed to remain in contact with the electrodes for 15minutes prior to the measurement.
Assay— Transfer an accurately measured volume of Oral Solution,equivalent to 100mg of doxepin,to a 100-mLvolumetric flask,dilute with dilute hydrochloric acid (1in 120)to volume,and mix.Dilute 4.0mLof this solution with the same solvent to 50.0mL.Transfer 15.0mLof the resulting solution to a 125-mLseparator,and extract with two 20-mLportions of ether.Dilute 10.0mLof the extracted aqueous phase with dilute hydrochloric acid (1in 120)to 25.0mL.Prepare a Standard solution from a suitable quantity of USP Doxepin Hydrochloride RS,by quantitative and stepwise dilution with dilute hydrochloric acid (1in 120)to obtain a solution having a known concentration of about 1.1mg per mL.Take a 4-mLaliquot of the Standard solution through the above-described procedure,beginning with “Dilute 4.0mLof this solution.”Concomitantly determine the absorbances of both solutions in 1-cm cells at the wavelength of maximum absorbance at about 292nm,with a suitable spectrophotometer,using dilute hydrochloric acid (1in 120)as the blank.Calculate the quantity,in mg,of doxepin (C19H21NO)in each mLof the Oral Solution taken by the formula:
0.885(0.1C/V)(AU/AS),
in which 0.885is the ratio of the molecular weight of doxepin to that of doxepin hydrochloride;Cis the concentration,in µg per mL,of USP Doxepin Hydrochloride RSin the Standard solution;Vis the volume,in mL,of Oral Solution taken;and AUand ASare the absorbances of the solution from the Oral Solution and the Standard solution,respectively.
Auxiliary Information— Staff Liaison:Salvador C.Salado,M.S.,Scientist and Latin American Liaison
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 695
Pharmacopeial Forum:Volume No.29(6)Page 1875
Phone Number:1-301-816-8165