Escitalopram 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

Escitalopram Oral Solution contains an amount of escitalopram oxalate equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of escitalopram (C₂₀H₂₁FN₂O).

2 IDENTIFICATION

A. The retention time of the major 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

3 ASSAY

Change to read:

PROCEDURE

Buffer: 6.1 g/L of monobasic potassium phosphate. To each liter of this solution add 1.5 mL of triethylamine. Adjust with phosphoric acid to a pH of 2.5.

Mobile phase: Acetonitrile and Buffer (32:68)

Diluent: Acetonitrile and Buffer (25:75)

Standard solution: #32 µg/mL of USP Escitalopram Oxalate RS (equivalent to 25 µg/ml, of escitalopram) (USP 1-May-2021) in Diluent

Sample solution: Nominally 25 µg/ml, of escitalopram from a suitable volume of Oral Solution, prepared as follows. Transfer a suitable portion of Oral Solution to an appropriate volumetric flask. Add 50% of the flask volume of (USP 1-May-2021) Diluent, and sonicate for 10 min with intermittent shaking. Allow the solution to cool, and dilute with Diluent to volume.

Chromatographic system

(See Chromatography (621), System Suitability)

Mode: LC

Detector: UV 240 nm. For Identification 8, use a diode array detector in the range of 210-400 nm (USP 1-May-2021)

Column: 4.6-mm x 25-cm; 5-um packing L1

Flow rate: 2 mL/min

Injection volume: 20 µl.

Run time: NLT 2.1 times the retention time of escitalopram

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0% 

Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response of escitalopram from the Sample solution

r_S = peak response of escitalopram from the Standard solution

C_S = concentration of USP Escitalopram Oxalate RS in the Standard solution (µg/mL)

C_U = nominal concentration of escitalopram in the Sample solution (ug/ml)

M_r1 = molecular weight of escitalopram, 324.39

M_r2 = molecular weight of escitalopram oxalate, 414.43

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Deliverable Volume (698): Meets the requirements

5 IMPURITIES

Change to read:

LIMIT OF CITALOPRAM RELATED COMPOUND B

Dilute phosphoric acid: Transfer 5 ml of phosphotic acid to a 50-ml. volumetric flask containing about 25 ml of water Cool and dilute with water to volume (USP 1-May-2021)

Solution A: 6.8 g/L of monobasic potassium phosphate Adjust (USP 1-May-2021) with Dilute phosphoric acid to a pH of 3.0.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Diluent: Acetonitrile and Solution A (30:70)

Standard solution: 0.6 µg/mL of USP Escitalopram Oxalate RS (equivalent to 0.5 µg/mL of escitalopram) (USP 1-May-2021) in Diluent

System suitability solution: 0.6 µg/mL of USP Citalopram Related Compound B. RS in Standard solution

Sample solution: Nominally 250 µg/mL (USP 1-May-2021) of escitalopram from a suitable volume of Oral Solution in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 237 nm

Column temperature: 45°

Flow rate: 0.5 mL/min

Injection volume: 20 µL

System suitability

Samples: Standard solution and System suitability solution

[NOTE-The relative retention times for citalopram related compound B and escitalopram are about 0.81 and 1.0, respectively. Use the System suitability solution to identify citalopram related compound BA 

Suitability requirements

Resolution: NLT 2.0 between citalopram related compound B and escitalopram, 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 citalopram related compound B in the portion of Oral Solution taken:

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

r_U = peak response of citalopram related compound B from the Sample solution

r_S = peak response of escitalopram from the Standard solution

C_S = concentration of USP Facitalopram CoalRS in the Standard solution (μg/mL)

C_U = nominal concentration of escitalopram in the Sample solution (μg/mL)

M_r1 = molecular weight of escitalopram, 324.39

M_r2 = molecular weight of escitalopram malate, 414.43

Acceptance criteria: NMT 0.2%

Change to read:

Organic Impurities

Solution A: 6.6 g/L of dibasic ammonium phosphate in water. To each iter of this solution add 2 ml of tracthylamiz. Adjust with phasutisoc acid in a pt of

Solution B: Acetonitole and methanc (60:40)

Mobile phase: See Table 2

Diluent: Acetonstole and Solution A (30:70)

Standard stock solution: 320 μg/mL of USP Escitalopram Oxalate RS (equivalent to 250 μg/mL of escitalopram) in Diluent

System suitability solution: 1.0 μg/mL of USP Citalopram Related Compound C RS in Standard stock solution

Standard solution: 3.2 μg/mL of USP Escitalopram Oxalate RS (equivalent to 2.5 μg/mL of escitalopram) from Standard stock solution in Diluent

Sensitivity solution: 0.32 μg/mL of USP Escitalopram Oxalate RS (equivalent to 0.25 μg/mL of escitalopram) from Standard solution in Diluent

Sample solution: Nominally 250 μg/mL of escitalopram from a suitable volume of Oral Solution in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 15-cm; 3-μm packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 μL

System suitability

Samples: Spotem suitability solution, Standard solution, and Sensitivity solution JUSP M-00211

Sultability requirements

Resolution: NLT 2.0 between citalopram related compound Cand escitalopram, System stability solution

Talling factor: NMT 2.0 for esichalopram, Syssem autability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10. Sensitivity solution SPM2021)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Oral Solution taken:

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

r_U = peak response of each individual impunty from the Sample solution

r_S = peak response of escitalopram from the Standard solution

C_S = concentration of USP Escitalopram Oxalate RS in the Standard solution (μg/mL)

C_U = nominal concentration of escitalopram in the Sample solution (μg/mL)

M_r1 = molecular weight of escitalopram, 324.39

M_r2 = molecular weight of escitalopram zalate 414.43

F = relative response factor for each individual impurity (see Table 3)

Acceptance criteria: See Table 3. The reporting threshold is 0.10%.

^a Not included in total impurities. For identification purposes only.

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

^c Process impurity listed for information only. Do not include in total impurities.

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

^e This impurity is monitored and controlled using the test for Limit of Citalopram Related Compound B. It is listed here for identification purposes only.

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

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

^h 1-(3-Dimethylaminopropyl)-1-(4-fluororphenyl)-1,3-dihydroisobenzofuran-5-carbonitrile-N-oxide.

ⁱ N-Chloromethyl-3-[5-cyano-1-(4-flurorphenyl)-1,3-dihydroisobenzofuran-1-yl]-N,N-dimethylpropan-1-ammonium chloride.

^j 3-[5-Cyano-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl]-N-{5-cyano-2-[4-(dimethylamino)-1-(4-fluorophenyl)but-1-enyl]benzyl}-N,N-dimethylpropan-1-ammonium chloride.

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

^l Sum of all impurities from the tests for Organic Impurities and Limit of Citalopram Related Compound B.

6 SPECIFIC TESTS

pH (791): 4.0-5.0

MICROBIAL ENUMERATION TESTS (61) and TESTS FOR SPECIFIED MICROORGANISMS (62): The total aerobic microbial count does not exceed 102 cfu/mL

The total yeasts and molds count does not exceed 10¹ cfu/ml. It meets the requirement of the test for absence of Escherichia coli.

7 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in light-resistant containers. Store at controlled room temperature.