Citalopram Tablets
» Citalopram Tablets contain an amount of Citalopram Hydrobromide equivalent to not less than 90.0 percent and not more than 110.0 percent of the labeled amount of citalopram free base (C20H21FN2O).
Packaging and storage
Preserve in well-closed containers. Store at controlled room temperature.
USP Reference standards 11
USP Citalopram Hydrobromide RS . USP Citalopram Related Compound A RS . USP Citalopram Related Compound B RS . USP Citalopram Related Compound C RS . USP Citalopram Related Compound E RS . USP Citalopram Related Compound F RS .
Identification
A: Infrared Absorption
Test specimen
Extract finely ground Tablet powder containing about 200 mg of citalopram with 30 mL of water, and filter. Add 1 mL of 1 N sodium hydroxide to the filtrate, and extract with 50 mL of cyclohexane by shaking for 10 minutes. Pass the cyclohexane layer through a silicone-treated filter paper into a beaker. Reduce the filtrate down to 3 mL, using gentle heat as necessary. Transfer the hot solution to a small centrifuge tube. Induce crystallization while cooling by scratching the side of the test tube with a spatula. Centrifuge the mixture, and decant off the cyclohexane. Dry the residue under vacuum in a desiccator. 197K Mix approximately 2 mg of the residue with approximately 300 mg of potassium bromide, and record the IR spectrum.
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.
Dissolution 711
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.
Uniformity of dosage units 905:
meet the requirements.
procedure for content uniformity
Buffer, Diluent, Internal standard solution, Mobile phase, and Chromatographic system
Proceed as directed in the Assay.
Test solution
Transfer 1 Tablet to a 100-mL volumetric flask, add 10 mL of Buffer, and shake by mechanical means until disintegrated. Add 40 mL of methanol, and sonicate for about 5 minutes. Allow to cool to room temperature. Add sufficient volume of Internal standard solution, and dilute, stepwise if necessary, with Diluent to volume to obtain a Test solution having a concentration of about 0.1 mg per mL of citalopram and 0.025 mg per mL of internal standard. Pass a portion of this solution through a membrane filter (PVDF) having a 0.45-µm or finer porosity, and use the filtrate.
Standard solution
Use the Standard preparation, prepared as directed in the Assay.
Procedure
Proceed as directed in the Assay. Calculate the quantity, in mg, of C20H21FN2O in the portion of sample taken by the formula:
100(CV)(RU / RS)(324.39/405.30)
in which C is the concentration, in mg per mL, of USP Citalopram Hydrobromide RS in the Standard solution; V is the final volume, in mL, required to obtain the Test solution; RU and RS are the ratios of peak responses of citalopram to the internal standard in the Test solution and the Standard solution, respectively; and 324.39 and 405.30 are the molecular weights of citalopram and citalopram hydrobromide, respectively.
Related compounds
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. [noteFor 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:
100(ri / rS)(324.39 / 405.30)(CS / CT)(1/F)
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.
Table 1
Assay
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:
100(CS / CU)(324.39/405.30)(RU / RS)
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.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
Chromatographic Column
USP32NF27 Page 1949
Pharmacopeial Forum: Volume No. 33(1) Page 46
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.
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