A: Infrared Absorption 197K.

B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.

C: Dissolve 0.10 g in 2 mL of alcohol, and add 1 mL of 2 N nitric acid and 3 drops of silver nitrate TS: a white precipitate is formed, and it dissolves on the dropwise addition of ammonium hydroxide.

Mobile phase, System suitability solution, Standard preparation, and Chromatographic system— Proceed as directed in the Assay.

Standard solution— Dissolve accurately weighed quantities of USP Imipramine Hydrochloride RS and USP Iminodibenzyl RS in acetonitrile, and dilute with a mixture of water and acetonitrile (5:3) to obtain a solution having known concentrations of about 2.5 µg of each component per mL.

Test solution— Transfer about 63 mg of Imipramine Hydrochloride, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with a mixture of water and acetonitrile (5:3), and mix.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. The relative retention times are about 0.8 for N-(dimethylaminopropyl) iminostilbene and 1.0 for imipramine. Calculate the percentage of iminodibenzyl in the portion of Imipramine Hydrochloride taken by the formula: in which C is the concentration, in µg per mL, of USP Iminodibenzyl RS in the Standard solution; W is the weight, in mg, of Imipramine Hydrochloride taken to prepare the Test solution; and rU and rS are the iminodibenzyl peak responses obtained from the Test solution and the Standard solution, respectively: not more than 0.1% of iminodibenzyl is found. Calculate the percentage of each other impurity in the portion of Imipramine Hydrochloride taken by the formula: in which C is the concentration, in µg per mL, of USP Imipramine Hydrochloride RS in the Standard solution; W is the weight, in mg, of Imipramine Hydrochloride taken to prepare the Test solution; ri is the peak response of each individual impurity, excluding iminodibenzyl, obtained from the Test solution, and rS is the peak response of imipramine obtained from the Standard solution: not more than 0.1% of N-(dimethylaminopropyl)iminostilbene is found; not more than 0.2% of any other impurity is found; and the total of all impurities found is not more than 1.0%.

(Official January 1, 2007)

Mobile phase— Prepare a filtered and degassed mixture of 0.06 M sodium perchlorate, acetonitrile, and triethylamine (625:375:1), and adjust with perchloric acid to a pH of 2.0. Make adjustments if necessary (see System Suitability under Chromatography 621).

System suitability solution— Transfer about 15 mg of USP Imipramine Hydrochloride RS and about 15 mg of USP Desipramine Hydrochloride RS, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with a mixture of water and acetonitrile (5:3) to volume, and mix.

Standard preparation— Dissolve an accurately weighed quantity of USP Imipramine Hydrochloride RS in a mixture of water and acetonitrile (5:3) to obtain a solution having a known concentration of about 0.3 mg per mL.

Assay preparation— Transfer about 30 mg of Imipramine Hydrochloride, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with a mixture of water and acetonitrile (5:3) to volume, and mix.

Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 269-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The column temperature is maintained at 40, and the flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between the imipramine and desipramine peaks is not less than 1.3. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0% for imipramine.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the quantity, in mg, of C19H24N2·HCl in the portion of Imipramine Hydrochloride taken by the formula: in which C is the concentration, in mg per mL, of USP Imipramine Hydrochloride RS in the Standard preparation; and rU and rS are the imipramine peak responses obtained from the Assay preparation and the Standard preparation, respectively.