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
•  pH 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.
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in light-resistant containers at controlled room temperature.
•  USP Reference Standards 11
USP Citalopram Hydrobromide RS Click to View Structure
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
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