Venlafaxine Tablets
DEFINITION
Venlafaxine Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of venlafaxine free base (C17H27NO2).
IDENTIFICATION
• A. Ultraviolet Absorption 
197U
197U
Diluent:
Methanol and 0.1 N hydrochloric acid (4:1)
Sample solution:
Dissolve a quantity of finely powdered Tablets, equivalent to 75 mg of venlafaxine, with 200 mL of Diluent, then sonicate for 30 min. Dilute with Diluent to 250 mL. Centrifuge a portion at 4000 rpm for 10 min. Dilute a portion of the filtrate with Diluent to make an approximate 1-in-2.5 solution. Pass a portion through a suitable 0.45-µm membrane filter.
Wavelength range:
250–350 nm
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the test for Organic Impurities.
ASSAY
• Procedure
Buffer:
3.4 g of potassium dihydrogen phosphate in 700 mL of water. Add 5 mL of triethylamine, and adjust with phosphoric acid to a pH of 3.0.
Diluent:
Methanol and 0.1 N hydrochloric acid (4:1)
Mobile phase:
Acetonitrile and Buffer (3:7)
Standard solution:
0.34 mg/mL of USP Venlafaxine Hydrochloride RS in Diluent
Sample solution:
0.3 mg/mL of venlafaxine in Diluent (from NLT 20 finely powdered Tablets). [Note—Sonicate for 30 min. ] Centrifuge a portion at 4000 rpm for 10 min. Pass a portion of the supernatant through a 0.45-µm membrane filter.
Chromatographic system
Mode:
LC
Detector:
UV 275 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Flow rate:
1.0 mL/min
Injection size:
10 µL
Run time:
5 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 label claim of C17H27NO2 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 USP Venlafaxine Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of venlafaxine in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of venlafaxine, 277.40 |
| Mr2 | = | = molecular weight of venlafaxine hydrochloride, 313.86 |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
711
Medium:
Water; 900 mL, deaerated
Apparatus 2:
50 rpm
Time:
30 min
Standard stock solution:
0.95 mg/mL of USP Venlafaxine Hydrochloride RS in methanol
Standard solution:
28.5 µg/mL of USP Venlafaxine Hydrochloride RS in Medium from the Standard stock solution
Sample solution:
Pass a portion of the solution under test through a suitable 0.45-µm filter.
Detector:
UV 275 nm
Path length:
1 cm
Blank:
Medium
Analysis:
Calculate the percentage of venlafaxine dissolved:
Result = (AU/AS) × (CS/L) × V × (Mr1/Mr2) × 100
| AU | = | = absorbance from the Sample solution |
| AS | = | = absorbance from the Standard solution |
| CS | = | = concentration of USP Venlafaxine Hydrochloride RS in the Standard solution (mg/mL) |
| L | = | = label claim (mg) |
| V | = | = volume of Medium, 900 mL |
| Mr1 | = | = molecular weight of venlafaxine, 277.40 |
| Mr2 | = | = molecular weight of venlafaxine hydrochloride, 313.86 |
Tolerances:
NLT 80% (Q) of the labeled amount of venlafaxine is dissolved.
• Uniformity of Dosage Units 905:
Meets the requirements
905:
Meets the requirements
IMPURITIES
Organic Impurities
• Procedure
Buffer:
Proceed as directed in the Assay.
Solution A:
Acetonitrile and Buffer (1:4)
Solution B:
Acetonitrile and Buffer (7:13)
Diluent:
Acetonitrile and Buffer (3:7)
Standard stock solution:
0.6 mg/mL of USP Venlafaxine Hydrochloride RS in Diluent
Standard solution:
1.8 µg/mL of USP Venlafaxine Hydrochloride RS in Diluent from the Standard stock solution
System suitability solution:
1.8 µg/mL of USP Venlafaxine Related Compound A RS in the Standard stock solution
Sample solution:
Equivalent to 0.6 mg/mL of venlafaxine (from NLT 20 finely powdered Tablets) in the Diluent. [Note—Sonicate, if necessary. ] Centrifuge a portion at 4000 rpm for 10 min. Pass a portion through a suitable 0.45-µm membrane filter.
Mobile phase:
See the gradient table below.
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 100 | 0 |
| 5 | 100 | 0 |
| 25 | 0 | 100 |
| 30 | 0 | 100 |
| 32 | 100 | 0 |
| 45 | 100 | 0 |
Chromatographic system
Mode:
LC
Detector:
UV 225 nm
Column:
4.6-mm × 25-cm; 5-µm packing L7
Flow rate:
1.0 mL/min
Injection size:
20 µL
System suitability
Samples:
Standard solution and System suitability solution
Suitability requirements
Resolution:
NLT 1.5 between venlafaxine related compound A and the venlafaxine peaks, System suitability solution
Tailing factor:
NMT 1.8, Standard solution
Relative standard deviation:
NMT 10.0%, 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) × (Mr1/Mr2) × (1/F) × 100
| rU | = | = peak response for the individual impurity from the Sample solution |
| rS | = | = peak response of venlafaxine from the Standard solution |
| CS | = | = concentration of USP Venlafaxine Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of venlafaxine in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of venlafaxine, 277.40 |
| Mr2 | = | = molecular weight of venlafaxine hydrochloride, 313.86 |
| F | = | = relative response factor (see Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 1.0%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Descyclohexanol venlafaxinea | 0.4 | 0.6 | 0.20 |
| Venlafaxine related compound Ab | 0.9 | — | — |
| Venlafaxine | 1.0 | — | — |
| Any unspecified degradation product | — | 1.0 | 0.20 |
|
a
2-(4-Methoxyphenyl)-N,N-dimethylethylamine.
b
1-(1-(4-Methoxyphenyl)-2-(methylamino)ethyl)cyclohexanol.
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers and store at controlled room temperature.
• USP Reference Standards 11
11
USP Venlafaxine Hydrochloride RS 
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USP Venlafaxine Related Compound A RS
1-(1-(4-methoxyphenyl)-2-(methylamino)ethyl)cyclohexanol.
C16H25NO2 263.38
1-(1-(4-methoxyphenyl)-2-(methylamino)ethyl)cyclohexanol.
C16H25NO2 263.38
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Hariram Ramanathan, M.S.
Associate Scientific Liaison 1-301-816-8313 |
(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 5009
Pharmacopeial Forum: Volume No. 35(6) Page 1483