Escitalopram Tablets
DEFINITION
Escitalopram Tablets contain an amount of escitalopram oxalate equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of C20H21FN2O.
IDENTIFICATION
• 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
Buffer:
1.5 g of anhydrous sodium acetate and 0.4 mL of glacial acetic acid in 1 L of water. Adjust with 1 M sodium hydroxide to a pH of 5.2.
Mobile phase:
Methanol, acetonitrile, and Buffer (33:7:60)
System suitability solution:
6.2 µg/mL of USP Citalopram Hydrobromide RS (equivalent to 5 µg/mL of citalopram) and 1 µg/mL of USP Citalopram Related Compound C RS in Mobile phase
Standard solution:
0.62 mg/mL of USP Citalopram Hydrobromide RS in Mobile phase (equivalent to 0.5 mg/mL of citalopram)
Sample solution:
Transfer 10 Tablets to a suitable volumetric flask, add Buffer to 10% of the final volume, and shake vigorously for 10 min. Add methanol to 50% of the final volume, shake for 1 additional min, sonicate for 10 min, and dilute with Mobile phase to volume to obtain a solution having a concentration of about 0.5 mg/mL of escitalopram.
Chromatographic system
Mode:
LC
Detector:
UV 239 nm
Column:
4.6-mm × 10-cm; 3-µm packing L1
Column temperature:
45
Flow rate:
1 mL/min
Injection size:
10 µL
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 3.0 between citalopram and citalopram related compound C, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of C20H21FN2O in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| CU | = | = nominal concentration of the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of citalopram, 324.39 |
| Mr2 | = | = molecular weight of citalopram hydrobromide, 405.30 |
Acceptance criteria:
90.0–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Medium:
0.1 N hydrochloric acid; 900 mL
Apparatus 2:
50 rpm
Time:
30 min
Standard solution 1:
3 µg/mL of USP Citalopram Hydrobromide RS in Medium
Standard solution 2:
15 µg/mL of USP Citalopram Hydrobromide RS in Medium
Standard solution 3:
30 µg/mL of USP Citalopram Hydrobromide RS in Medium
Sample solution:
Pass a portion of the solution through a suitable filter of 0.45-µm pore size.
Spectrometric conditions
Mode:
UV-Vis
Analytical wavelength:
239 nm
Path length:
0.5 cm
Blank:
Medium
System suitability
Samples:
Standard solution 1, Standard solution 2, and Standard solution 3
Suitability requirements
Correlation coefficient:
NLT 0.995, determined using Standard solution 1, Standard solution 2, and Standard solution 3, three replicates of each solution
Relative standard deviation:
NMT 2.0%, determined using Standard solution 3, six replicates
Analysis
Samples:
Standard solution 1, Standard solution 2, Standard solution 3, and Sample solution
Generate a calibration curve using the data from Standard solution 1, Standard solution 2, and Standard solution 3. Determine the concentration, CU, in mg/mL, of citalopram hydrobromide in the Sample solution using the calibration curve.
Calculate the percentage of citalopram dissolved:
Result = (CU/L) × (Mr1/Mr2) × V × 100
| CU | = | = concentration of citalopram hydrobromide in the Sample solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| Mr1 | = | = molecular weight of citalopram, 324.39 |
| Mr2 | = | = molecular weight of citalopram hydrobromide, 405.30 |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of escitalopram is dissolved.
• Uniformity of Dosage Units 905:
Meets the requirements
905:
Meets the requirements
IMPURITIES
• Organic Impurities
Buffer, 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 3.0 between citalopram and citalopram related compound C, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × (Mr1/Mr2) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of citalopram from the Standard solution |
| CS | = | = concentration of USP Citalopram Hydrobromide RS in the Standard solution |
| CU | = | = nominal concentration of the Sample solution |
| F | = | = relative response factor (see Impurity Table 1) |
| Mr1 | = | = molecular weight of citalopram, 324.39 |
| Mr2 | = | = molecular weight of citalopram hydrobromide, 405.30 |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 2.0%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Citalopram related compound Aa | 0.33 | 0.84 | 0.3 |
| Citalopram related compound Bb | 0.56 | 0.78 | 0.5 |
| Citalopram related compound Cc
(3-oxocitalopram) |
0.80 | 0.51 | 0.5 |
| Escitalopram | 1.0 | — | — |
| Citalopram related compound Ed (citalopram N-oxide) | 1.4 | 0.94 | 0.2 |
| Any other individual, unspecified impurity | — | 1.0 | 0.1 |
|
a
1-(3-Dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carboxamide.
b
1-(3-Dimethylaminopropyl)-1-(4-fluorophenyl)-3-hydroxy-1,3-dihydroisobenzofuran-5-carbonitrile; 3-hydroxycitalopram.
c
3-(3-Dimethylaminopropyl)-3-(4-fluorophenyl)-6-cyano-1(3H)-isobenzofuranone.
d
1-(3-Dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile-N-oxide.
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers. Store at controlled room temperature.
• USP Reference Standards 11
11
USP Citalopram Hydrobromide RS 
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USP Citalopram Related Compound C RS
3-(3-Dimethylaminopropyl)-3-(4-fluorophenyl)-6-cyano-1(3H)-isobenzofuranone.
C20H19FN2O2 338.22
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3-(3-Dimethylaminopropyl)-3-(4-fluorophenyl)-6-cyano-1(3H)-isobenzofuranone.
C20H19FN2O2 338.22
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 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3096
Pharmacopeial Forum: Volume No. 36(4) Page 917