Citalopram Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION 

Citalopram Tablets contain an amount of citalopram hydrobromide equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of citalopram free base (C₂₀H₂₁FN₂O). 

2 IDENTIFICATION 

Change to read: 

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020) 

Sample: Extract finely ground Tablet powder containing 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 min. 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. [Note—If crystallization fails to occur in the above procedure, use the following alternative procedure. Extract finely ground Tablet powder containing about 50 mg of citalopram with 10 mL of chloroform in a test tube, and sonicate for 1 min. Centrifuge for 10 min, and filter into a beaker. Evaporate to dryness with nitrogen and, if necessary, induce crystallization by etching the beaker.] 

Mix approximately 2 mg of the residue with approximately 300 mg of potassium bromide, and record the IR spectrum. Acceptance criteria: Meet the requirements 

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. 

3 ASSAY 

Procedure 

Buffer: 1.42 g/L of anhydrous dibasic sodium phosphate in water 

Diluent: Methanol and Buffer (80:20) 

Mobile phase: 0.77 mg/mL of dodecyltrimethylammonium bromide in Diluent 

Internal standard solution: 0.25 mg/mL of USP Citalopram Related Compound F RS in Diluent 

Standard stock solution: 1.25 mg/mL of USP Citalopram Hydrobromide RS in Diluent 

Standard solution: 0.025 mg/mL of USP Citalopram Related Compound F RS and 0.125 mg/mL of USP Citalopram Hydrobromide RS from the Internal standard solution and the Standard stock solution, respectively, in Diluent 

Sample solution: 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 min. Allow to cool to room temperature, and then dilute with Diluent to volume. Before taking an aliquot for dilution, allow to stand until the residue settles. Transfer a volume of the clear supernatant to a 50-mL volumetric flask to obtain a nal nominal concentration between 0.090 and 0.10 mg/mL of citalopram. Add 5.0 mL of Internal standard solution, and dilute with Diluent to volume. Pass a portion through a filter (PTFE) having a 0.45-µm or finer pore size. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L1 

Column temperature: 45° 

Flow rate: 1 mL/min 

Injection volume: 10 µL 

System suitability 

Sample: Standard solution 

[Note—The relative retention times for citalopram related compound F and citalopram are about 1.36 and 1.0, respectively.] Suitability requirements 

Resolution: NLT 1.5 between citalopram and citalopram related compound F 

Column efficiency: NLT 2000 theoretical plates, calculated from the citalopram peak 

Relative standard deviation: NMT 1.5% for the peak response ratio of citalopram to the internal standard 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of citalopram (C₂₀H₂₁FN₂O) in the portion of Tablets taken: 

Result = (r_U/r_S) × (C_S/C_U) × (M_r1 /M_r2) × 100 

r_U = peak response ratio of citalopram to the internal standard from the Sample solution

r_S = peak response ratio of citalopram to the internal standard from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

C_U = nominal concentration of the Sample solution (mg/mL) 

M_r1 = molecular weight of citalopram free base, 324.39 

M_r2 = molecular weight of citalopram hydrobromide, 405.30 

Acceptance criteria: 90.0%–110.0% 

4 PERFORMANCE TESTS 

Dissolution 〈711〉 

Buffer: 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) 

Medium: Buffer; 800 mL, deaerated 

Apparatus 1: 100 rpm 

Time: 30 min 

Standard solution: 12 µg/mL of USP Citalopram Hydrobromide RS in Medium 

Sample solution: Sample per Dissolution 〈711〉. Pass through a PVDF filter having a 0.45-µm pore size, and dilute with Medium as needed. 

Instrumental conditions 

(See Ultraviolet-Visible Spectroscopy 〈857〉.) 

Mode: UV 

Analytical wavelength: 239 nm 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of citalopram (C₂₀H₂₁FN₂O) dissolved: 

Result = (A_U/A_S) × C_S x V x D × (M_r1 /M_r2) × 100 

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

V = volume of Medium, 800 mL

D = dilution factor of the Sample solution

M_r1 = molecular weight of citalopram  324.39 

M_r2 = molecular weight of citalopram hydrobromide, 405.30 

L = label claim of citalopram (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of citalopram (C₂₀H₂₁FN₂O) is dissolved. 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 IMPURITIES 

Organic Impurities 

Buffer: 3.15 g/L of monobasic potassium phosphate and 3.60 g/L of dibasic sodium phosphate dodecahydrate (Na₂HPO₄. 12H₂O) in water Mobile phase: Methanol, acetonitrile, and Buffer (38:7:55). Adjust with phosphoric acid to a pH of 6.5. 

Standard stock solution: 0.25 mg/mL of USP Citalopram Hydrobromide RS in Mobile phase 

System suitability solution: 1 µg/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 in the Standard stock solution Standard solution: 0.625 µg/mL of citalopram hydrobromide from the Standard stock solution in Mobile phase Sensitivity solution: 0.05 µg/mL of citalopram hydrobromide from the Standard solution in Mobile phase 

Sample solution: 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 a mixture of methanol and water (1:1), mix, and sonicate for about 5 min. Allow to cool, dilute with a mixture of methanol and water (1:1) to volume, and mix thoroughly. Allow the excipients to settle. Dilute with Mobile phase, as necessary, to a nal concentration of 0.5 mg/mL of citalopram. Pass a portion of this solution through a polytetrafluoroethylene (PTFE) membrane filter having a 0.45-µm or finer pore size, and use the filtrate. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 239 nm 

Column: 4.6-mm × 15-cm; 5-µm packing L1 

Column temperature: 45° 

Flow rate: 0.8 mL/min 

Injection volume: 20 µL 

System suitability 

Samples: System suitability solution, Standard solution, and Sensitivity solution 

[Note—See Table 1 for the relative retention times.] 

Suitability requirements 

Resolution: NLT 3 between citalopram related compound C and citalopram, System suitability solution 

Tailing factor: NMT 1.5, Standard solution 

Relative standard deviation: NMT 5.0%, Standard solution 

Signal-to-noise ratio: NLT 3, Sensitivity solution 

Analysis 

Samples: System suitability solution, Standard solution, and Sample solution 

Chromatograph the System suitability solution, and identify the components on the basis of their relative retention times given in Table 1. Calculate the percentage of each impurity in the portion of Tablets taken: 

Acceptance criteria: See Table 1. 

Table 1 

6 ADDITIONAL REQUIREMENTS 

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 

1-(3-Dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carboxamide. 

C₂₀H₂₃FN₂O₂ 342.22 

USP Citalopram Related Compound B RS 

1-(3-Dimethylaminopropyl)-1-(4-uorophenyl)-3-hydroxy-1,3-dihydroisobenzofuran-5-carbonitrile oxalate. 

C₂₀H₂₁FN₂O₂  · C₂H₂O₄ 430.43 

USP Citalopram Related Compound C RS 

3-(3-Dimethylaminopropyl)-3-(4-uorophenyl)-6-cyano-1(3H)-isobenzofuranone oxalate. 

C₂₀H₁₉FN₂O₂  · C₂H₂O₄ 428.42 

USP Citalopram Related Compound E RS 

1-(3-Dimethylaminopropyl)-1-(4-uorophenyl)-1,3-dihydrobenzofuran-5-carbonitrile-N-oxide hydrochloride. 

C₂₀H₂₁FN₂O₂  · HCl 376.85 

USP Citalopram Related Compound F RS 

Dimethyl-(1-methyl-3,3-diphenylallyl)amine hydrochloride. 

C₂₀H₂₁ N · HCl 287.83