Venlafaxine Hydrochloride
(ven'' la fax' een hye'' droe klor' ide).
C17H27NO2·HCl 313.86 Cyclohexanol, 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]-, hydrochloride; (±)-1-[-[(Dimethylamino)methyl]-p-methoxybenzyl]cyclohexanol hydrochloride [99300-78-4]. DEFINITION
Venlafaxine Hydrochloride contains NLT 98.0% and NMT 102.0% of C17H27NO2·HCl, calculated on the dried basis.
IDENTIFICATION
• A. Infrared Absorption 197K
[NoteIf the spectra obtained in the solid state show differences, dissolve the substance to be examined and the Reference Standard separately in methanol or 2-propanol, evaporate to dryness, and record new spectra of the residues. ]
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
• C. Identification TestsGeneral, Chloride 191:
Meets the requirements
ASSAY
• Procedure
Solution A:
Phosphoric acid and water (1:10)
Buffer:
3.4 g of monobasic potassium phosphate in 700 mL of water. Adjust with Solution A to a pH of 3.0.
Diluent:
Acetonitrile and water (1:1)
Mobile phase:
Acetonitrile and Buffer (3:7)
Standard solution:
0.04 mg/mL of USP Venlafaxine Hydrochloride RS in Diluent
Sample solution:
0.04 mg/mL of Venlafaxine Hydrochloride in Diluent
Chromatographic system
Mode:
LC
Detector:
UV 225 nm
Column:
4.6-mm × 25-cm; 5-µm packing L7
Flow rate:
1.5 mL/min
Column temperature
30 ± 2
Injection size:
20 µL
Run time:
2 times the retention time of the venlafaxine peak
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C17H27NO2·HCl in the portion of Venlafaxine Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
98.0%102.0% on the dried basis
IMPURITIES
Inorganic Impurities
• Residue on Ignition 281:
NMT 0.1%
• Heavy Metals, Method I or Method II 231:
NMT 20 ppm
Organic Impurities
• Procedure
Buffer and Mobile phase:
Proceed as directed in the Assay.
System suitability solution:
0.5 mg/mL of USP Venlafaxine Hydrochloride RS and 1.5 µg/mL of USP Venlafaxine Related Compound A RS in Mobile phase
Standard solution:
1 µg/mL of USP Venlafaxine Hydrochloride RS in Mobile phase
Sample solution:
1 mg/mL of Venlafaxine Hydrochloride in Mobile phase
Chromatographic system
Mode:
LC
Detector:
UV 225 nm
Column:
4.6-mm × 25-cm; 5-µm packing L7
Column temperature:
30 ± 2
Flow rate:
0.7 mL/min
Injection size:
10 µL
Run time:
7 times the retention time of the venlafaxine peak
System suitability
Sample:
System suitability solution
Suitability requirements
Resolution:
NLT 1.5 between venlafaxine and venlafaxine related compound A
Relative standard deviation:
NMT 2.0% for the venlafaxine peak
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of any individual impurity in the portion of Venlafaxine Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 0.5%
Impurity Table 1
SPECIFIC TESTS
• Loss on Drying 731:
Dry a sample in vacuum at 105 for 3 h: it loses NMT 0.5% of its weight.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers and store at controlled room temperature.
• USP Reference Standards 11
USP Venlafaxine Related Compound A RS
1-(1-(4-methoxyphenyl)-2-(methylamino)ethyl)cyclohexanol. C16H25NO2 263.38
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 5008
Pharmacopeial Forum: Volume No. 35(6) Page 1482
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