Citalopram Oral Solution

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 Oral Solution contains an amount of citalopram hydrobromide equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of citalopram free base (C₂₀H₂₁FN₂O). It may contain a suitable preservative. 

2 IDENTIFICATION 

A. The retention time of the citalopram peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. Add the following: 

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.2S (USP41) 

3 ASSAY 

Change to read: Procedure 

Solution A: Methanol and acetonitrile(10:90)2S (USP41) 

Buffer: 6.1 g/L of monobasic potassium phosphate in water. Add 1.5 mL of triethylamine per liter of the solution. Adjust with phosphoric acid to a pH of 2.5. 

Mobile phase: Solution A and Buffer (28:72)2S (USP41) 

Diluent: Acetonitrile and Buffer (25:75)2S (USP41) 

Standard solution: 0.25 mg/mL of USP Citalopram Hydrobromide RS,  equivalent to 0.2 mg/mL of citalopram free base in Diluent2S (USP41) Sample solution: Nominally equivalent to 0.2 mg/mL of citalopram free base, prepared as follows. Transfer a suitable volume of Oral Solution to a suitable volumetric flask.2S (USP41) Add 50% of the flask volume of Diluent, and sonicate at room temperature for 3 min with intermittent shaking. Allow the solution to cool, and dilute with Diluent to volume. [Note—The Sample solution may be passed through either a PVDF or nylon membrane filter of suitable pore size.] 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 240 nm. For Identification B, use a diode array detector in the range of 210–400 nm.2S (USP41) Column: 4.6-mm × 15-cm; 5-µm packing L1 

Column temperature: 40° 

Flow rate: 1.5 mL/min 

Injection volume: 10 µL 

Run time: NLT2S (USP41) 2 times the retention time of citalopram 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2.5 

Relative standard deviation: NMT 0.73%2S (USP41) 

Analysis 

Samples: Standard solution and Sample solution 

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

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

r_U = peak response of citalopram from the Sample solution 

r_S = peak response of citalopram from the Standard solution 

C_S = concentration of USP Citalopram Hydrobromide RS in the Standard solution (mg/mL) 

C_U = nominal concentration of citalopram in 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% of citalopram free base (C₂₀H₂₁FN₂O) 

4 MPURITIES 

Change to read: 

Organic Impurities 

Solution A: Acetonitrile, methanol, and tetrahydrofuran(85:5:10)2S (USP41) 

Buffer: Dissolve 3.0 g of octanesulfonic acid sodium salt2S (USP41) in 1 L of water. Add 2 mL of triethylamine and 5 mL of tetrabutylammonium hydroxide, 40 percent in water.2S (USP41) Mix, and adjust with phosphoric acid to a pH of 3.0. Mobile phase: Solution A and Buffer (25:75)2S (USP41) 

Diluent: Acetonitrile and water(25:75)2S (USP41) 

System suitability solution: 6 µg/mL of USP Citalopram Related Compound D RS and 1.3 mg/mL of USP Citalopram Hydrobromide RS in Diluent 

Standard solution: 0.0063 mg/mL2S (USP41) of USP Citalopram Hydrobromide RS in Diluent 

Sample solution: Nominally equivalent to 1 mg/mL of citalopram free base, prepared as follows. Transfer a suitable volume of Oral Solution to a suitable volumetric flask.2S (USP41) Add 60% of the flask volume of Diluent, and sonicate at room temperature for 3 min with intermittent shaking. Allow the solution to cool, and dilute with Diluent to volume. [Note—The Sample solution may be passed through either a PVDF or nylon membrane filter of suitable pore size.] 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 225 nm 

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

Flow rate: 1.5 mL/min 

Injection volume: 20 µL 

Run time: NLT2S (USP41) 2.6 times the retention time of citalopram for the System suitability solution and the Standard solution; NLT2S (USP41) 5.7 times the retention time of citalopram for the Sample solution 

System suitability 

Samples: System suitability solution and Standard solution 

Suitability requirements 

Resolution: NLT 1.8 between citalopram and citalopram related compound D, System suitability solution 

Tailing factor: NMT 2.0, Standard solution 

Relative standard deviation: NMT 5.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each degradation product2S (USP41) in the portion of Oral Solution taken: 

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × (M_r1 /M_r2) × 100 

r_U = peak response of each degradation product from the Sample solution 

r_S = peak response of citalopram from the Standard solution 

C_S = concentration of USP Citalopram Hydrobromide RS in the Standard solution (mg/mL) 

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

F = relative response factor for each degradation product

M_r1 = molecular weight of citalopram free base, 324.39 

M_r2 = molecular weight of citalopram hydrobromide, 405.30 

Acceptance criteria: See Table 1. 

Table 1 

^a 1-(3-Dimethylaminopropyl)-1-(4-uorophenyl)-1,3-dihydroisobenzofuran-5-carboxamide. 

^b 1-[3-(Dimethylamino)propyl]-1-(4-uorophenyl)-1,3-dihydroisobenzofuran-5-carboxylic acid. 

^c 1-[3-(Dimethylamino)propyl]-1-phenyl-1,3-dihydroisobenzofuran-5-carbonitrile. 

^d This process impurity is included in the table for Identification only. It is controlled in the drug substance, and is not to be reported or included in the total degradation products2S (USP41) for the drug product. 

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

^f 3-[5-Chloro-1-(4-uorophenyl)-1,3-dihydroisobenzofuran-1-yl]-N,N-dimethylpropan-1-amine. 

^g 3-[5-Bromo-1-(4-uorophenyl)-1,3-dihydroisobenzofuran-1-yl]-N,N-dimethylpropan-1-amine. 

5 SPECIFIC TESTS 

Deliverable Volume 〈698〉: Meets the requirements 

pH 〈791〉: 3.5–7.0 

Change to read: 

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count does not exceed 102 cfu/mL.2S (USP41) The total yeasts and molds count does not exceed 5 × 101 cfu/mL. It meets the requirements of the test for the absence of Escherichia coli. 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in light-resistant containers at controlled room temperature. 

USP Reference Standards 〈11〉 

USP Citalopram Hydrobromide RS 

USP Citalopram Related Compound D RS 

[Note—May be available as a hydrochloride or hydrobromide salt.] 

1-(4-Fluorophenyl)-1-(3-methylaminopropyl)-1,3-dihydroisobenzofuran-5-carbonitrile hydrochloride. 

C₁₉H₁₉FN₂O· HCl 346.83 

1-(4-Fluorophenyl)-1-(3-methylaminopropyl)-1,3-dihydroisobenzofuran-5-carbonitrile hydrobromide. C₁₉H₁₉FN₂O· HBr 391.28