Escitalopram Oxalate

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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S-(+)-5-Isobenzofurancarbonitrile, 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-, oxalate;

S-(+)-1-[3-(Dimethylamino)propyl]-1-(p-fluorophenyl)-5-phthalancarbonitrile oxalate CAS RN^®: 219861-08-2; UNII: 5U85DBW7LO.

1 DEFINITION

Escitalopram Oxalate contains NLT 98.0% and NMT 102.0% of Escitalopram oxalate (C₂₀H₂₁FN₂O · C₂H₂O₄), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

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: 3.4 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid or sodium hydroxide solution to a pH of 3.0 before final dilution.

Solution A: Acetonitrile and Buffer (10:90)

Solution B: Acetonitrile and Buffer (65:35)

Mobile phase: See Table 1

[Note-The gradient was established on an HPLC system with a dwell volume of approximately 1.6 mL]

System suitability solution: 2 µg/mL each of USP Escitalopram Oxalate RS and USP Citalopram Related Compound D. RS in Solution A

Standard solution: 0.5 mg/mL of USP Escitalopram Oxalate RS in Solution A

Sample solution: 0.5 mg/ml of Escitalopram Oxalate in Solution A

Chromatographic system

(See Chromatography (621), System Surtability)

Mode: LC

Detector: UV 237 nm

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

Column temperature: 45°

Flow rate: See Table 1.

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between escitalopram and citalopram related compound D, System suitability solution

Tailing factor: 0.8-3, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of escitalopram oxalate (C₂₀H₂₁FN₂O · C₂H₂O₄) in the portion of Escitalopram Oxalate taken

Result = (r_U/(r_S) × (C_S /C_U) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 98.0%-102.0% on the anhydrous basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

ENANTIOMERIC PURITY

Buffer: Dissolve 6.8 g of monobasic potassium phosphate in 250 ml of water, add 150 mL of 0.2 N sodium hydroxide, adjust with phosphoric

acid or sodium hydroxide solution to a pH of 7.0, and dilute with water to 1 L

Mobile phase: Acetonitrile and Buffer (15:85)

System suitability solution: 125 µg/ml. each of USP R-Citalopram Oxalate RS and USP Escitalopram Oxalate RS in Mobile phase

Sample solution: 125 µg/ml. of Escitalopram Oxalate in Mobile phase

Chromatographic system

(See Chromatography (621). System Suitability)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm × 15-cm; 5-μm packing L57

Column temperature: 30°

Flow rate: 0.6 mL/min

Injection volume: 15 μl

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 1.3 between R-citalopram and escitalopram

Tailing factor: 0.8-2.5 for escitalopram

Analysis

Sample: Sample solution

Calculate the percentage of R-citalopram oxalate in the portion of Escitalopram Oxalate taken:

Result = (r_u/r_T) x 100

r_u = peak response of R-citalopram from the Sample solution

r_T = sum of peak responses of R-citalopram and escitalopram from the Sample solution

Acceptance criteria: NMT 3.0%

ORGANIC IMPURITIES

Buffer, Solution A, Solution B, Mobile phase, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution A: 2 µg/ml. each of USP Escitalopram Oxalate RS and USP Citalopram Related Compound D RS in Solution A

System suitability solution 8: 0.5 mg/ml of USP Escitalopram Oxalate RS in Solution A

System suitability

Samples: System suitability solution A and System suitability solution B

Suitability requirements

Resolution: NLT 1.5 between escitalopram and citalopram related compound D, System suitability solution A

Tailing factor: 0.8-3, System suitability solution B

Relative standard deviation: NMT 2.0%, System suitability solution B

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Escitalopram Oxalate taken.

Result = (r_u/r_T) x (1/F) x100

r_u = peak response of each impurity from the Sample solution 

r_T = peak response of escitalopram from the Sample solution 

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

^a Included for identification only. This peak is due to the oxalate counterion and hence is not an impurity.

^b 1-(3-Dimethylaminopropyl)-1-(4′-fluorophenyl)-5-(4-dimethylaminobutyryl)-1,3-dihydroisobenzofuran.

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

^d 1-(3-Dimethylaminopropyl)-1-(4-fluorophenyl)-3-hydroxy-1,3-dihydroisobenzofuran-5-carbonitrile.

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

^f 1-(3-Dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile-N-oxide.

5 SPECIFIC TESTS

Water Determination, Method Ia (921): NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.