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Clomipramine Hydrochloride Capsules
» Clomipramine Hydrochloride Capsules contain not less than 90.0 percent and not more than 110.0 percent of clomipramine hydrochloride (C19H23ClN2·HCl).
Packaging and storage— Preserve in well-closed containers.
Identification, Infrared Absorption 197K—
Test specimen— Transfer the contents of a number of Capsules, equivalent to about 125 mg of clomipramine hydrochloride, to a suitable container, add 25 mL of chloroform, stir for 5 minutes, and filter. Evaporate on a steam bath to a volume of about 5 mL, chill in an ice bath, add ethyl ether, and stir until crystals form. Filter, and dry at 100 for 1 hour.
Dissolution 711—
Medium: 0.1 N hydrochloric acid; 500 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Procedure— Determine the amount of C19H23ClN2·HCl dissolved by employing UV absorption at the wavelength of maximum absorbance at about 252 nm 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 RS in the same Medium.
Tolerances— Not less than 80% (Q) of the labeled amount of C19H23ClN2·HCl is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
PROCEDURE FOR CONTENT UNIFORMITY—
Standard solution— Prepare a solution of USP Clomipramine Hydrochloride RS in methanol having a known concentration of about 30 µg per mL.
Test solution— Quantitatively transfer the contents of 1 Capsule to a 100-mL volumetric flask with the aid of methanol, add about 75 mL of methanol, shake by mechanical means for 1 hour, 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 30 µg per mL.
Procedure— Concomitantly determine the absorbances of the Standard solution and the Test solution in 1-cm cells, at the wavelength of maximum absorbance at about 252 nm, 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 T is the labeled quantity, in mg, of clomipramine hydrochloride in the Capsule; C is the concentration, in µg per mL, of USP Clomipramine Hydrochloride RS in the Standard solution; D is 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 AU and AS are the absorbances of the Test solution and the Standard solution, respectively.
Residual solvents 467: meet the requirements.
(Official January 1, 2007)
Assay—
Sodium 1-heptanesulfonate solution, Mobile phase, System suitability solution, Standard preparation, and Chromatographic system— Proceed as directed in the Assay under Clomipramine Hydrochloride.
Assay preparation— Remove as completely as possible the contents of not fewer than 20 Capsules. Transfer an accurately weighed portion of the contents, equivalent to about 160 mg of clomipramine hydrochloride, to a 200-mL volumetric flask, add 130 mL of methanol, shake by mechanical means for 1 hour, and dilute with methanol to volume. Transfer 10 mL of this solution to a 25-mL volumetric flask, dilute with methanol to volume, mix, and filter.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into 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 C is the concentration, in mg per mL, of USP Clomipramine Hydrochloride RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Ravi Ravichandran, Ph.D., Senior Scientist
Expert Committee : (MDPP05) Monograph Development-Psychiatrics and Psychoactives
USP29–NF24 Page 554
Pharmacopeial Forum : Volume No. 28(1) Page 52
Phone Number : 1-301-816-8330