Escitalopram Oxalate
(es'' sye tal' oh pram ox' a late).
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C20H21FN2O·C2H2O4 414.43
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      [219861-08-2].
DEFINITION
Escitalopram Oxalate contains NLT 98.0% and NMT 102.0% of C20H21FN2O·C2H2O4, calculated on the anhydrous basis.
IDENTIFICATION
•  B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
•  Procedure
Solution A:  3.4 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid or sodium hydroxide solution to a pH of 3.0 prior to final dilution.
Solution B:  Acetonitrile and Solution A (1:9)
Solution C:  Acetonitrile and Solution A (13:7)
Mobile phase:  See the gradient table below.
Time
(min)
Solution B
(%)
Solution C
(%)
Flow Rate
(mL/min)
0 95 5 1
35 65 35 1
45 0 100 1
45.1 0 100 2
60 0 100 2
60.1 95 5 1
68 95 5 1
[Note—The gradient was established on an HPLC system with a dwell volume of approximately 1.6 mL. The injection time can be adjusted relative to the start of a run to accommodate changes in dwell volume from one HPLC system to another to achieve the separation described. ]
System suitability solution:  2 µg/mL each of USP Escitalopram Oxalate RS and USP Citalopram Related Compound D RS in Solution B
Standard solution:  0.5 mg/mL of USP Escitalopram Oxalate RS in Solution B
Sample solution:  0.5 mg/mL of Escitalopram Oxalate in Solution B
Chromatographic system 
Mode:  LC
Detector:  UV 237 nm
Column:  4.6-mm × 25-cm; 5-µm packing L1
Column temperature:  45
Flow rate:  See the gradient table above.
Injection size:  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 percent of C20H21FN2O·C2H2O4 in the portion of Escitalopram Oxalate taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== concentration of the Standard solution (mg/mL)
CU== concentration of the Sample solution (mg/mL)
Acceptance criteria:  98.0–102.0% on the anhydrous basis
IMPURITIES
Inorganic Impurities 
•  Residue on Ignition 281: NMT 0.1%
•  Heavy Metals, Method II 231: NMT 20 ppm
Organic Impurities 
Solution A, Solution B, Solution C, Mobile phase, System suitability solution, Standard solution, Sample solution, and Chromatographic system:  Proceed as directed in the Assay.
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 
Sample:  Sample solution
Calculate the percentage of each impurity in the portion of Escitalopram Oxalate taken:
Result = (rU/rS) × (1/F) × 100
rU== peak response of each impurity from the Sample solution
rS== peak response of escitalopram from the Sample solution
F== relative response factor (see Impurity Table 1)
Acceptance criteria 
Individual impurities:  See Impurity Table 1.
Total impurities:  NMT 0.5%
Impurity Table 1
Name Relative
Retention
Time
Relative
Response
Factor
Acceptance
Criteria,
NMT (%)
5-Dimethylaminobutyryl citaloprama 0.40 0.34 0.2
Citalopram related compound Ab 0.50 0.79 0.1
Citalopram related compound Bc
(3-hydroxy
citalopram)
0.74 1.0 0.1
Citalopram related compound Cd
(3-oxocitalopram)
0.90 0.79 0.1
Citalopram related compound De (desmethyl citalopram) 0.97 1.0 0.1
Escitalopram 1.0
Citalopram related compound Ef (citalopram
N-oxide)
1.1 1.0 0.1
Individual
unspecified
impurity
1.0 0.1
a  1-(3-Dimethylaminopropyl)-1-(4¢-fluorophenyl)-5-(4-dimethylaminobutyryl)-1,3-dihydroisobenzofuran.
b  1-(3-Dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carboxamide.
c  1-(3-Dimethylaminopropyl)-1-(4-fluorophenyl)-3-hydroxy-1,3-dihydroisobenzofuran-5-carbonitrile.
d  3-(3-Dimethylaminopropyl)-3-(4-fluorophenyl)-6-cyano-1(3H)-isobenzofuranone.
e  1-(4-Fluorophenyl)-1-(3-methylaminopropyl)-1,3-dihydroisobenzofuran-5-carbonitrile.
f  1-(3-Dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile-N-oxide.
SPECIFIC TESTS
•  Enantiomeric Purity
Solution A:  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 Solution A (3:17)
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 
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 size:  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 = (rU/rS) × 100
rU== peak response of R-citalopram from the Sample solution
rS== peak response of escitalopram from the Sample solution
Acceptance criteria:  NMT 3.0%
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in well-closed containers.
•  USP Reference Standards 11
USP R-Citalopram Oxalate RS
[(R)-1-[3-(dimethylamino)propyl]-1-(p-fluorophenyl)-5-phthalancarbonitrile oxalate]
    C20H21FN2O·C2H2O4        414.43
USP Citalopram Related Compound D RS Click to View Structure
[1-(4-fluorophenyl)-1-(3-methylaminopropyl)-1,3-dihydroisobenzofuran-5-carbonitrile hydrochloride]
    C19H19FN2O·HCl        346.83
USP Escitalopram Oxalate RS Click to View Structure
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Ravi Ravichandran, Ph.D.
Principal Scientific Liaison
1-301-816-8330
(SM42010) Monographs - Small Molecules 4
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 3094
Pharmacopeial Forum: Volume No. 36(3) Page 668