Venlafaxine Hydrochloride

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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C₁₇H₂₇NO₂ · HCI           313.86.

Cyclohexanol, 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]-, hydrochloride;

(±)-1-[α-[(Dimethylamino)methyl]-p-methoxybenzyl cyclohexanol hydrochloride    CAS RN^®: 99300-78-4; UNII: 707RX5A8MO.

DEFINITION

Venlafaxine Hydrochloride contains NLT 98.0% and NMT 102.0% of venlafaxine hydrochloride (C₁₇H₂₇NO₂ · HCI), calculated on the dried basis.

1 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K_{▲(CN 1-MAY-2020)}

[NOTE-If the spectra obtained in the solid state show differences, dissolve the substance to be examined and the Reference Standard

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 TESTS GENERAL, Chloride (191): Meets the requirements

2 ASSAY

PROCEDURE

Solution A: Phosphoric acid and water (1:10)

Diluent: Acetonitrile and water (50:50)

Mobile phase: Acetonitrile and Buffer (30:70)

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 225 nm

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

Column temperature: 30 ± 2°

Flow rate: 1.5 mL/min

Injection volume: 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 venlafaxine hydrochloride (C₁₇H₂₇NO₂ · HCI) in the portion of Venlafaxine Hydrochloride 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 USP Venlafaxine Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of Venlafaxine Hydrochloride in the Sample solution (mg/mL) Cu

Acceptance criteria: 98.0%-102.0% on the dried basis

3 IMPURITIES

3.1 RESIDUE ON IGNITION (281)

NMT 0.1%

3.2 ORGANIC IMPURITIES

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: 0.001 mg/mL of USP Venlafaxine Hydrochloride RS in Mobile phase

Sample solution: 1 mg/mL of Venlafaxine Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 225 nm

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

Column temperature: 30 ± 2°

Flow rate: 0.7 mL/min

Injection volume: 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 = (r_U/r_S) × (C_S/C_U) × (1/F) x 100

r_U = peak response of each individual impurity 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 = concentration of Venlafaxine Hydrochloride in the Sample solution (mg/mL)

F = relative response factor for the corresponding impurity peak (see Table 1)

Acceptance criteria: See Table 1.

Table 1

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

^b 1-[2-Amino-1-(4-methoxyphenyl)ethyl cyclohexanol.

^c 2-Cyclohexyl-2-(4-methoxyphenyl)-N,N-dimethylethylamine.

4 SPECIFIC TESTS

LOSS ON DRYING (731)

Analysis: Dry under vacuum at 105° for 3 h.

Acceptance criteria: NMT 0.5%

5 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