Venlafaxine Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Venlafaxine Tablets contain an amount of venlafaxine hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of venlafaxine free base (C₁₇H₂₇NO₂).

2 IDENTIFICATION

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 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 (80:20)

Mobile phase: Acetonitrile and Buffer (30:70)

Standard solution: 0.3 mg/mL of venlafaxine free base from a suitable quantity of USP Venlafaxine Hydrochloride RS in Diluent

Sample solution: Nominally 0.3 mg/mL of venlafaxine (from NLT 20 finely powdered Tablets) in Diluent. Sonicate for 30 min. Centrifuge and pass a portion of the supernatant through a suitable membrane filter of 0.45-µm pore size. [NOTE-A centrifuge speed of 4000 rpm for 10 min may be suitable.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 275 nm. For Identification A, use a diode array detector in the range of 200-400 nm.

Column: 4.6-mm x 25-cm; 5-µm packing L1

Flow rate: 1.0 mL/min

Injection volume: 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 the labeled amount of venlafaxine free base (C₁₇H₂₇NO₂) in the portion of Tablets taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of venlafaxine free base in the Standard solution (mg/mL)

C_U = nominal concentration of venlafaxine in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0% of the labeled amount of venlafaxine free base (C₁₇H₂₇NO₂)

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711),

Medium: Water, deaerated; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Standard stock solution: 0.84 mg/mL of venlafaxine free base from a suitable quantity of USP Venlafaxine Hydrochloride RS in methanol

Standard solution: (L/1000) mg/mL of venlafaxine free base in Medium, where L is the label claim in mg/Tablet, from the Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

Detector: UV 275 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of venlafaxine free base (C₁₇H₂₇NO₂) dissolved:

                         Result = (A_U/A_S) × (C_S/L) × V × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of venlafaxine free base in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of venlafaxine free base (C₁₇H₂₇NO₂) is dissolved. solved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Buffer: Prepare as directed in the Assay.

Solution A: Acetonitrile and Buffer (20:80)

Solution B: Acetonitrile and Buffer (35:65)

Diluent: Acetonitrile and Buffer (30:70)

Mobile phase: See Table 1.

Table 1

System suitability solution: 0.0018 mg/mL of USP Venlafaxine Related Compound A RS and 0.6 mg/mL of USP Venlafaxine Hydrochloride RS in Diluent

Standard stock solution: 0.6 mg/mL of USP Venlafaxine Hydrochloride RS in Diluent

Standard solution: 0.0018 mg/mL of USP Venlafaxine Hydrochloride RS in Diluent from the Standard stock solution

Sample solution: Nominally 0.6 mg/mL of venlafaxine (from NLT 20 finely powdered Tablets) in Diluent. Centrifuge and pass a portion through a suitable membrane filter of 0.45-µm pore size. [NOTE-Sonicate, if necessary. A centrifuge speed of 4000 rpm for 10 min may be suitable.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm x 25-cm; 5-µm packing L7

Flow rate: 1.0 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between venlafaxine related compound A and venlafaxine, 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 individual degradation product in the portion of Tablets taken:

                         Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) x (1/F) x 100

r_U = peak response of each individual degradation product from the Sample solution

r_S = peak response of venlafaxine from the Standard solution

C_S = concentration of USP Venlafaxine Hydrochloride RS in the Standard solution (mg/mL)

C_U = nominal concentration of venlafaxine in the Sample solution (mg/mL)

M_r1 = molecular weight of venlafaxine, 277.40

M_r2 = molecular weight of venlafaxine hydrochloride, 313.86 

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a 2-(4-Methoxyphenyl)-N,N-dimethylethylamine.

^b Process impurity, included for system suitability and identification only. Controlled in the drug substance and is not to be reported or included in the total degradation products for the drug product.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers, and store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Venlafaxine Hydrochloride RS

USP Venlafaxine Related Compound A RS

1-(1-(4-Methoxyphenyl)-2-(methylamino) ethyl) cyclohexanol hydrochloride.

C₁₆H₂₅NO₂ · HCI           299.84