Citalopram Oral Solution
DEFINITION
Citalopram Oral Solution contains an amount of citalopram hydrobromide equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of citalopram free base (C20H21FN2O). It may contain a suitable preservative.
IDENTIFICATION
• Procedure:
The retention time of the citalopram peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Solution A:
Methanol and acetonitrile (1:9)
Buffer:
6.1 g/L of monobasic potassium phosphate in water. Add 1.5 mL of triethylamine per L of the solution. Adjust with phosphoric acid to a pH of 2.5.
Mobile phase:
Solution A and Buffer (7:18)
Diluent:
Acetonitrile and Buffer (1:3)
Standard solution:
0.25 mg/mL of USP Citalopram Hydrobromide RS
Sample solution:
Transfer a suitable volume of Oral Solution to a suitable volumetric flask to obtain 0.2 mg/mL final concentration of citalopram free base. Add 50% of the flask volume of Diluent, and sonicate at room temperature for 3 min with intermittent shaking. Allow the solution to cool, and dilute with Diluent to volume. [Note—The Sample solution may be filtered through either a PVDF or nylon membrane filter of suitable pore size. ]
Chromatographic system
Mode:
LC
Detector:
UV 240 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Column temperature:
40
Flow rate:
1.5 mL/min
Injection size:
10 µL
Run time:
2 times the retention time of citalopram
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.5
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C20H21FN2O in the portion of Oral Solution taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response of citalopram from the Sample solution |
| rS | = | = peak response of citalopram from the Standard solution |
| CS | = | = concentration of USP Citalopram Hydrobromide RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of citalopram in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of citalopram free base, 324.39 |
| Mr2 | = | = molecular weight of citalopram hydrobromide, 405.30 |
Acceptance criteria:
90.0%–110.0% of citalopram free base (C20H21FN2O)
IMPURITIES
Organic Impurities
• Procedure
Solution A:
Acetonitrile, methanol, and tetrahydrofuran (17:1:2)
Buffer:
Dissolve 3.0 g of 1-octane sulphonic acid sodium salt in 1 L of water. Add 2 mL of triethylamine and 5 mL of tetra-n-butyl ammonium hydroxide, 40 percent in water. Mix and adjust with phosphoric acid to a pH of 3.0.
Mobile phase:
Solution A and Buffer (1:3)
Diluent:
Acetonitrile and water (1:3)
System suitability solution:
6 µg/mL of USP Citalopram Related Compound D RS and 1.3 mg/mL of USP Citalopram Hydrobromide RS in Diluent
Standard solution:
6.3 µg/mL of USP Citalopram Hydrobromide RS in Diluent
Sample solution:
Transfer a suitable volume of the Oral Solution to a suitable volumetric flask to obtain 1 mg/mL final concentration of citalopram. Add 60% of the flask volume of Diluent, and sonicate at room temperature for 3 min with intermittent shaking. Allow the solution to cool, and dilute with Diluent to volume. [Note—The Sample solution may be filtered through either a PVDF or nylon membrane filter of suitable pore size. ]
Chromatographic system
Mode:
LC
Detector:
UV 225 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
1.5 mL
Injection size:
20 µL
Run time:
2.6 times the retention time of citalopram for the System suitability solution and Standard solution; 5.7 times the retention time of citalopram for the Sample solution
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 1.8 between citalopram and citalopram related compound D, 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 any individual impurity in the portion of Oral Solution taken:
Result = (rU/rS) × (CS/CU) × (1/F) × (Mr1/Mr2) × 100
| rU | = | = peak response of each individual 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 (mg/mL) |
| CU | = | = nominal concentration of citalopram in the Sample solution (mg/mL) |
| F | = | = relative response factor for each impurity as listed in Impurity Table 1 |
| Mr1 | = | = molecular weight of citalopram free base, 324.39 |
| Mr2 | = | = molecular weight of citalopram hydrobromide, 405.30 |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 0.50%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Citalopram related compound Aa |
0.29 | 0.86 | 0.20 |
| Carboxyl citalopramb | 0.47 | 0.72 | 0.20 |
| Desfluoro citalopramc,h | 0.71 | — | — |
| Citalopram related compound Cd |
0.83 | 1.85 | 0.20 |
| Citalopram | 1.0 | — | — |
| Citalopram related compound De |
1.11 | 0.95 | 0.20 |
| Citalopram related compound Gf,h |
3.13 | — | — |
| Citalopram related compound Hg,h |
3.75 | — | — |
| Any individual unspecified degradation product |
— | — | 0.15 |
|
a
1-(3-Dimethylaminopropyl)-1-(4¢-fluorophenyl)-1,3-dihydroisobenzofuran-5-carboxamide.
b
1-[3-(Dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carboxylic acid.
c
1-[3-(Dimethylamino)propyl]-1-phenyl-1,3-dihydroisobenzofuran-5-carbonitrile.
d
3-(3-N,N-Dimethylamino)-1-(4-fluorophenyl)-6-cyano-1(3H)-isobenzofuranone.
e
1-(4-Fluorophenyl)-1-(3-methylaminopropyl)-1,3-dihydroisobenzofuran-5-carbonitrile.
f
1-(4-Fluorophenyl)-1-(3-dimethylaminopropyl)-5-chlorophthalane hydrobromide.
g
1-(4-Fluorophenyl)-1-(3-dimethylaminopropyl)-5-bromophthalane hydrobromide.
h
This process impurity is listed for information only.
|
|||
SPECIFIC TESTS
• Deliverable Volume 
698
:
Meets the requirements
698:
Meets the requirements
• pH 791:
3.5–7.0
791:
3.5–7.0
• Microbial Enumeration Tests 61 and Tests for Specified Microorganisms 62:
The total aerobic microbial count does not exceed 100 cfu/mL. The total yeasts and molds count does not exceed 50 cfu/mL. It meets the requirements of the test for absence of Escherichia coli.
61 and Tests for Specified Microorganisms 62:
The total aerobic microbial count does not exceed 100 cfu/mL. The total yeasts and molds count does not exceed 50 cfu/mL. It meets the requirements of the test for absence of Escherichia coli.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in light-resistant containers at controlled room temperature.
• USP Reference Standards 11
11
USP Citalopram Hydrobromide RS 
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USP Citalopram Related Compound D RS
1-(4-Fluorophenyl)-1-(3-methylaminopropyl)-1,3-dihydroisobenzofuran-5-carbonitrile hydrochloride
C19H19FN2O·HCl 346.83
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1-(4-Fluorophenyl)-1-(3-methylaminopropyl)-1,3-dihydroisobenzofuran-5-carbonitrile hydrochloride
C19H19FN2O·HCl 346.83
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 |
| 61 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 62 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 2682
Pharmacopeial Forum: Volume No. 36(3) Page 657