A: Infrared Absorption

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.

Medium: pH 1.5 buffer (prepared by transferring 118 mL of 1 N hydrochloric acid and 82 mL of 1 N sodium hydroxide to a 1000-mL volumetric flask, diluting with water to volume, and adjusting with 1 N sodium hydroxide to a pH of 1.5); 800 mL, deaerated.

Apparatus 1: 100 rpm.

Time: 30 minutes.

Procedure— Determine the amount of citalopram hydrobromide dissolved by employing UV absorption at the wavelength of maximum absorbance at about 239 nm on portions of the solution under test passed through a 0.45-µm PVDF filter, suitably diluted with Medium, if necessary, in comparison with a Standard solution having a known concentration (about 12 µg per mL) of USP Citalopram Hydrobromide RS in the same Medium. Calculate the amount of citalopram dissolved, in percentage, by the formula: in which AU and AS are the absorbances obtained from the solution under test and the Standard solution, respectively; CS is the concentration, in mg per mL, of the Standard solution; 324.39 and 405.30 are the molecular weights of citalopram and citalopram hydrobromide, respectively; D is the dilution factor of the solution under test; 800 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and L is the tablet label claim, in mg, of citalopram.

Tolerances— Not less than 80% (Q) of the labeled amount of citalopram (C20H21FN2O) is dissolved in 30 minutes.

procedure for content uniformity—

Phosphate buffer— Dissolve 3.15 g of potassium dihydrogen phosphate and 3.60 g of disodium hydrogen phosphate (Na2HPO4·12H2O) in 1 L of water.

Mobile phase— Prepare a filtered and degassed mixture of Phosphate buffer, methanol, and acetonitrile (55:38:7). Adjust with phosphoric acid to a pH of 6.5. Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard stock solution— Dissolve an accurately weighed quantity of USP Citalopram Hydrobromide RS in Mobile phase to obtain a solution having a known concentration of about 0.5 mg per mL.

Standard solution— Prepare a solution having a concentration of 0.625 µg per mL of citalopram hydrobromide through stepwise dilution of the Standard stock solution with Mobile phase.

Sensitivity solution— Prepare a solution having a concentration of 0.05 µg per mL of citalopram hydrobromide through stepwise dilution of the Standard solution with Mobile phase.

Related compounds stock solutions— Separately dissolve accurately weighed quantities of USP Citalopram Related Compound A RS, USP Citalopram Related Compound B RS, USP Citalopram Related Compound C RS, and USP Citalopram Related Compound E RS in Mobile phase to obtain stock solutions having known concentrations of about 0.1 mg per mL of each compound.

Peak identification solution— Prepare a mixture containing about 0.001 mg per mL each of USP Citalopram Related Compound A RS, USP Citalopram Related Compound B RS, USP Citalopram Related Compound C RS, and USP Citalopram Related Compound E RS, using the Standard stock solution as the diluent.

Resolution solution— Dilute 0.5 mL of Citalopram related compound C stock solution and 25.0 mL of the Standard stock solution with Mobile phase to 50 mL to obtain a solution containing 0.001 mg per mL of citalopram related compound C and 0.25 mg per mL of citalopram hydrobromide.

Test solution— Transfer 10 Tablets into a 200-mL volumetric flask, add 25 mL of Phosphate buffer, and shake by mechanical means until disintegrated. Add about 100 mL of a mixture of methanol and water (50:50), mix, and sonicate for about 5 minutes. Allow to cool, dilute with a mixture of methanol and water (50:50) to volume, and mix thoroughly. Allow the excipients to settle. Dilute as necessary to obtain a final concentration of 0.5 mg per mL of citalopram in Mobile phase based on the label claim. Pass a portion of this solution through a polytetrafluoroethylene (PTFE) membrane filter having a 0.45-µm or finer porosity, and use the filtrate.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 239-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The column temperature is maintained at 45. The flow rate is about 0.8 mL per minute. Inject the Standard solution, and record the peak responses as directed for Procedure: the citalopram peak shows no shoulders or excessive tailing; the capacity factor, k¢, is not less than 3.5; the column efficiency is not less than 5000 theoretical plates; the tailing factor is not more than 1.5; and the relative standard deviation of the response for replicate injections is not more than 5%. Inject the Sensitivity solution into the chromatograph, and verify that the signal-to-noise ratio is at least 3. Inject the Resolution solution, and record the peak responses as directed for Procedure: the resolution, R, between citalopram related compound C and citalopram is not less than 3. Inject the Peak identification solution, and record the responses as directed for Procedure: the four related compound peaks are baseline resolved from each other and the citalopram peak. [note—For identification purposes, approximate relative retention times are given in Table 1.]

Procedure— Inject a volume (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of each impurity in each Tablet by the formula: in which ri is the individual peak response for each citalopram related compound obtained from the Test solution; rS is the response of the corresponding peak in the Standard solution; 324.39 and 405.30 are the molecular weights of citalopram and citalopram hydrobromide, respectively; CS and CT are the concentrations, in mg per mL, of citalopram hydrobromide in the Standard solution and the Test solution, respectively; and F is the relative response factor of each impurity relative to citalopram (free base). The limits for the related compounds are listed in Table 1.

Buffer— Transfer about 0.71 g of anhydrous dibasic sodium phosphate to a 500-mL volumetric flask, and add about 250 mL of water. Shake to dissolve, then dilute with water to volume.

Diluent— Prepare a solution of methanol and Buffer (80:20).

Internal standard solution— Dissolve an accurately weighed amount of USP Citalopram Related Compound F RS in Diluent, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 0.25 mg per mL.

Mobile phase— Prepare a filtered and degassed solution of Diluent containing about 770 mg of dodecyltrimethylammonium bromide per L. Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard stock preparation— Dissolve an accurately weighed quantity of USP Citalopram Hydrobromide RS in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 1.25 mg of citalopram hydrobromide per mL.

Standard preparation— Pipet 5.0 mL of the Standard stock preparation and 5.0 mL of the Internal standard solution into a 50-mL volumetric flask. Dilute with Diluent to volume, and mix.

Assay preparation— Transfer 10 Tablets to a 200-mL volumetric flask, add 25 mL of Buffer, and shake by mechanical means until disintegrated. Add 100 mL of methanol, and sonicate for about 5 minutes. Allow to cool to room temperature, then dilute with Diluent to volume. Allow to stand until the residue settles before taking an aliquot for dilution. Transfer an accurately measured volume of the clear supernatant to a 50-mL volumetric flask to obtain a final concentration between 0.090 and 0.10 mg per mL of citalopram, based on the label claim. Add 5.0 mL of Internal standard solution, dilute with Diluent to volume, and mix. Pass a portion through a filter (PTFE) having a 0.45-µm or finer porosity.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1 mL per minute. The column temperature is maintained at 45. Inject the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 1.36 for citalopram related compound F and 1.0 for citalopram; the resolution, R, between citalopram and citalopram related compound F is not less than 1.5; the column efficiency is not less than 2000 theoretical plates, calculated from the citalopram peak; and the relative standard deviation for replicate injections is not more than 1.5% for the citalopram peak.

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 citalopram peaks. Calculate the quantity, in percent of label claim, of citalopram per Tablet taken by the formula: in which CS and CU are the concentrations, in mg per mL, of USP Citalopram Hydrobromide RS in the Standard preparation and Citalopram Hydrobromide in the Assay preparation, respectively; 324.39 and 405.30 are the molecular weights of citalopram and citalopram hydrobromide, respectively; and RU and RS are the ratios of the peak responses of citalopram to the internal standard obtained from the Assay preparation and the Standard preparation, respectively.