Clomipramine Hydrochloride Capsules
»Clomipramine Hydrochloride Capsules contain not less than 90.0percent and not more than 110.0percent of clomipramine hydrochloride (C19H23ClN2·HCl).
Packaging and storage— Preserve in well-closed containers.
Identification,Infrared Absorption á197Kñ—
Test specimen— Transfer the contents of a number of Capsules,equivalent to about 125mg of clomipramine hydrochloride,to a suitable container,add 25mLof chloroform,stir for 5minutes,and filter.Evaporate on a steam bath to a volume of about 5mL,chill in an ice bath,add ethyl ether,and stir until crystals form.Filter,and dry at 100for 1hour.
Dissolution á711ñ—
Medium: 0.1Nhydrochloric acid;500mL.
Apparatus 2: 50rpm.
Time: 30minutes.
Procedure— Determine the amount of C19H23ClN2·HCl dissolved by employing UVabsorption at the wavelength of maximum absorbance at about 252nm on 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 Clomipramine Hydrochloride RSin the same Medium.
Tolerances— Not less than 80%(Q)of the labeled amount of C19H23ClN2·HCl is dissolved in 30minutes.
Uniformity of dosage units á905ñ: meet the requirements.
PROCEDUREFOR CONTENT UNIFORMITY—
Standard solution— Prepare a solution of USP Clomipramine Hydrochloride RSin methanol having a known concentration of about 30µg per mL.
Test solution— Quantitatively transfer the contents of 1Capsule to a 100-mLvolumetric flask with the aid of methanol,add about 75mLof methanol,shake by mechanical means for 1hour,and dilute with methanol to volume.Further dilute an aliquot of this solution quantitatively,and stepwise if necessary,with methanol to obtain a solution having a concentration of about 30µg per mL.
Procedure— Concomitantly determine the absorbances of the Standard solutionand the Test solutionin 1-cm cells,at the wavelength of maximum absorbance at about 252nm,with a suitable spectrophotometer,using methanol as the blank.Calculate the quantity,in mg,of clomipramine hydrochloride (C19H23ClN2·HCl)in the Capsule taken by the formula:
(TC/D)(AU/AS),
in which Tis the labeled quantity,in mg,of clomipramine hydrochloride in the Capsule;Cis the concentration,in µg per mL,of USP Clomipramine Hydrochloride RSin the Standard solution;Dis the concentration,in µg per mL,of clomipramine hydrochloride in the Test solution,based on the labeled quantity per Capsule and the extent of dilution;and AUand ASare the absorbances of the Test solutionand the Standard solution,respectively.
Assay—
Sodium 1-heptanesulfonate solution,Mobile phase,System suitability solution,Standard preparation,andChromatographic system— Proceed as directed in the Assayunder Clomipramine Hydrochloride.
Assay preparation— Remove as completely as possible the contents of not fewer than 20Capsules.Transfer an accurately weighed portion of the contents,equivalent to about 160mg of clomipramine hydrochloride,to a 200-mLvolumetric flask,add 130mLof methanol,shake by mechanical means for 1hour,and dilute with methanol to volume.Transfer 10mLof this solution to a 25-mLvolumetric flask,dilute with methanol to volume,mix,and filter.
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 clomipramine hydrochloride (C19H23ClN2·HCl)in the portion of Capsules taken by the formula:
500C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Clomipramine Hydrochloride RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Salvador C.Salado,M.S.,Scientist and Latin American Liaison
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 510
Pharmacopeial Forum:Volume No.28(1)Page 52
Phone Number:1-301-816-8165