Citalopram Tablets
DEFINITION
Citalopram Tablets contain an amount of Citalopram Hydrobromide equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of citalopram free base (C20H21FN2O).
IDENTIFICATION
• A. Infrared Absorption 
197K
197K
Sample:
Extract finely ground Tablet powder containing 200 mg of citalopram with 30 mL of water, and filter. Add 1 mL of 1 N sodium hydroxide to the filtrate, and extract with 50 mL of cyclohexane by shaking for 10 min. Pass the cyclohexane layer through a silicone-treated filter paper into a beaker. Reduce the filtrate down to 3 mL, using gentle heat as necessary. Transfer the hot solution to a small centrifuge tube. Induce crystallization while cooling by scratching the side of the test tube with a spatula. Centrifuge the mixture, and decant off the cyclohexane. Dry the residue under vacuum in a desiccator. [Note—If crystallization fails to occur in the above procedure, use the following alternative procedure. Extract finely ground Tablet powder containing about 50 mg of citalopram with 10 mL of chloroform in a test tube, and sonicate for 1 min. Centrifuge for 10 min, and filter into a beaker. Evaporate to dryness with nitrogen and if necessary induce crystallization by etching the beaker. ]
Mix approximately 2 mg of the residue with approximately 300 mg of potassium bromide, and record the IR spectrum.
• 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
Buffer:
1.42 g/L of anhydrous dibasic sodium phosphate in water
Diluent:
Methanol and Buffer (80:20)
Mobile phase:
0.77 mg/mL of dodecyltrimethylammonium bromide in Diluent
Internal standard solution:
0.25 mg/mL of USP Citalopram Related Compound F RS in Diluent
Standard stock solution:
1.25 mg/mL of USP Citalopram Hydrobromide RS in Diluent
Standard solution:
0.025 mg/mL of USP Citalopram Related Compound F RS and 0.125 mg/mL of USP Citalopram Hydrobromide RS from the Internal standard solution and the Standard stock solution, respectively, in Diluent
Sample solution:
Transfer 10 Tablets to a 200-mL volumetric flask, add 25 mL of Buffer, and shake by mechanical means until disintegrated. Add 100 mL of methanol, and sonicate for about 5 min. Allow to cool to room temperature, then dilute with Diluent to volume. Allow to stand until the residue settles before taking an aliquot for dilution. Transfer a volume of the clear supernatant to a 50-mL volumetric flask to obtain a final nominal concentration between 0.090 mg/mL and 0.10 mg/mL of citalopram. Add 5.0 mL of Internal standard solution, and dilute with Diluent to volume. Pass a portion through a filter (PTFE) having a 0.45-µm or finer pore size.
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Column temperature:
45
Flow rate:
1 mL/min
Injection size:
10 µL
System suitability
Sample:
Standard solution
[Note—The relative retention times for citalopram related compound F and citalopram are about 1.36 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 1.5 between citalopram and citalopram related compound F
Column efficiency:
NLT 2000 theoretical plates, calculated from the citalopram peak
Relative standard deviation:
NMT 1.5% for the citalopram peak
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the label claim of citalopram in the portion of Tablets taken:
Result = (RU/RS) × (CS/CU) × (Mr1/Mr2) × 100
| RU | = | = ratio of the peak response of citalopram to the internal standard from the Sample solution |
| RS | = | = ratio of the peak response of citalopram to the internal standard 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
Buffer solution:
pH 1.5 buffer (prepared by transferring 118 mL of 1 N hydrochloric acid and 82 mL of 1 N sodium hydroxide to a 1000-mL volumetric flask, diluting with water to volume, and adjusting with 1 N sodium hydroxide to a pH of 1.5)
Medium:
Buffer solution; 800 mL, deaerated
Apparatus 1:
100 rpm
Time:
30 min
Detector:
UV at about 239 nm
Sample solution:
Sample per Dissolution 711. Pass through a PVDF filter having a 0.45-µm pore size, and dilute with Medium as needed.
711. Pass through a PVDF filter having a 0.45-µm pore size, and dilute with Medium as needed.
Standard solution:
12 µg/mL of USP Citalopram Hydrobromide RS in Medium
Analysis:
Calculate the percentage of citalopram dissolved:
Result = (AU/AS) × CS × D × V × (Mr1/Mr2) × (100/L)
| AU | = | = absorbance from the Sample solution |
| AS | = | = absorbance from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| D | = | = dilution factor of the Sample solution |
| V | = | = volume of Medium (800 mL) |
| Mr1 | = | = molecular weight of citalopram, 324.39 |
| Mr2 | = | = molecular weight of citalopram hydrobromide, 405.30 |
| L | = | = Tablet label claim of citalopram (mg) |
Tolerances:
NLT 80% (Q) of the labeled amount of C20H21FN2O is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Buffer:
3.15 g/L of potassium dihydrogen phosphate and 3.60 g/L of disodium hydrogen phosphate (Na2HPO4·12H2O) in water
Mobile phase:
Methanol, acetonitrile, and Buffer (38:7:55). Adjust with phosphoric acid to a pH of 6.5.
Standard stock solution:
0.25 mg/mL of USP Citalopram Hydrobromide RS in Mobile phase
System suitability solution:
1 µg/mL each of USP Citalopram Related Compound A RS, USP Citalopram Related Compound B RS, USP Citalopram Related Compound C RS, and USP Citalopram Related Compound E RS, in Standard stock solution
Standard solution:
0.625 µg/mL of citalopram hydrobromide from Standard stock solution in Mobile phase
Sensitivity solution:
0.05 µg/mL of citalopram hydrobromide from Standard solution in Mobile phase
Sample solution:
Transfer 10 Tablets to a 200-mL volumetric flask, add 25 mL of Buffer, and shake by mechanical means until disintegrated. Add 100 mL of a mixture of methanol and water (1:1), mix, and sonicate for about 5 min. Allow to cool, dilute with a mixture of methanol and water (1:1) to volume, and mix thoroughly. Allow the excipients to settle. Dilute with Mobile phase as necessary to obtain a final concentration of 0.5 mg/mL of citalopram. Pass a portion of this solution through a polytetrafluoroethylene (PTFE) membrane filter having a 0.45-µm or finer pore size, and use the filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 239 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Column temperature:
45
Flow rate:
0.8 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution, Standard solution, and Sensitivity solution
[Note—The relative retention times are given in Impurity Table 1. ]
Suitability requirements
Resolution:
NLT 3 between citalopram related compound C and citalopram, System suitability solution
Tailing factor:
NMT 1.5, Standard solution
Relative standard deviation:
NMT 5%, Standard solution
Signal-to-noise ratio:
NLT 3, Sensitivity solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in each Tablet taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × (1/F) × 100
| rU | = | = peak response for each citalopram related compound from the Sample solution |
| rS | = | = peak response of the corresponding peak in the Standard solution |
| CS | = | = concentration of citalopram hydrobromide in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of citalopram hydrobromide in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of citalopram, 324.39 |
| Mr2 | = | = molecular weight of citalopram hydrobromide, 405.30 |
| F | = | = relative response factor for each impurity relative to citalopram (free base) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 0.8%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Citalopram related compound A | 0.43 | 0.77 | 0.2 |
| Citalopram related compound B | 0.60 | 0.98 | 0.25 |
| Citalopram related compound C | 0.83 | 0.69 | 0.25 |
| Citalopram | 1.0 | — | — |
| Citalopram related compound E | 1.32 | 0.91 | 0.1 |
| Any other individual unidentified impurity | — | 1.0 | 0.2 |
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 A RS
1-(3-Dimethylaminopropyl)-1-(4¢-fluorophenyl)-1,3-dihydroisobenzofuran-5-carboxamide.
C20H23FN2O2 342.22
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1-(3-Dimethylaminopropyl)-1-(4¢-fluorophenyl)-1,3-dihydroisobenzofuran-5-carboxamide.
C20H23FN2O2 342.22
USP Citalopram Related Compound B RS
1-(3-Dimethylaminopropyl)-1-(4-fluorophenyl)-3-hydroxy-1,3-dihydroisobenzofuran-5-carbonitrile.
C20H21FN2O2 340.22
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1-(3-Dimethylaminopropyl)-1-(4-fluorophenyl)-3-hydroxy-1,3-dihydroisobenzofuran-5-carbonitrile.
C20H21FN2O2 340.22
USP Citalopram Related Compound C RS
3-(3-N,N-Dimethylamino)-1-(4-fluorophenyl)-6-cyano-1(3H)-isobenzofuranone.
C20H19FN2O2 338.22
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3-(3-N,N-Dimethylamino)-1-(4-fluorophenyl)-6-cyano-1(3H)-isobenzofuranone.
C20H19FN2O2 338.22
USP Citalopram Related Compound E RS
1-(3-Dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydrobenzofuran-5-carbonitrile-N-oxide.
C20H21FN2O2 340.22
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1-(3-Dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydrobenzofuran-5-carbonitrile-N-oxide.
C20H21FN2O2 340.22
USP Citalopram Related Compound F RS
Dimethyl-(1-methyl-3,3-diphenylallyl)amine hydrochloride.
C18H21NHCl 286.64
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Dimethyl-(1-methyl-3,3-diphenylallyl)amine hydrochloride.
C18H21NHCl 286.64
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 2684
Pharmacopeial Forum: Volume No. 35(4) Page 844