Desvenlafaxine Fumarate

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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C₁₆H₂₅NO₂ · C₄H₄O₄ · H₂O                397.46

C₁₆H₂₅NO₂ · C₄H₄O₄                 379.45

trans-Butenedioic acid, compound with 4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl)ethyl] phenol (1:1), monohydrate;

1-[2-(Dimethylamino)-1-(4-hydroxyphenyl)ethyl] cyclohexanol hydrogen (E)-but-2-enedioate monohydrate CAS RN^®: 313471-75-9; UNII: R5JHD7L72A.

Anhydrous CAS RN^®: 93414-04-1; UNII: ATX24E9M6L.

1 DEFINITION

Desvenlafaxine Fumarate contains NLT 98.0% and NMT 102.0% of desvenlafaxine fumarate (C₁₆H₂₅NO₂ · C₄H₄O₄), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K or 197A _{▲(ERR 1-Oct-2020)}

B. The retention times of the desvenlafaxine and fumaric acid peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 PROCEDURE

Buffer: To each liter of water, add 1 mL of triethylamine and adjust with phosphoric acid to a pH of 3.0.

Solution A: Acetonitrile and Buffer (10:90)

Solution B: Acetonitrile and Buffer (60:40)

Mobile phase: See Table 1.

Table 1

Diluent: Solution A and Solution B (50:50)

Standard solution: 0.05 mg/mL of USP Desvenlafaxine Fumarate RS in Diluent. Sonication may be used to promote dissolution.

Sample solution: 0.05 mg/mL of Desvenlafaxine Fumarate in Diluent. Sonication may be used to promote dissolution.

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability..)

Mode: LC

Detector: UV 225 nm

Column: 2.1-mm x 15-cm; 1.7-µm packing 11

Column temperature: 55°

Flow rate: 0.3 mL/min

Injection volume: 1 µL

3.1.2 System suitability

Sample: Standard solution

[NOTE-The relative retention times for fumaric acid and desvenlafaxine are 0.48 and 1.0, respectively.]

3.1.3 Suitability requirements

Tailing factor: NMT 2.5

Relative standard deviation: NMT 1.0%

3.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of desvenlafaxine fumarate (C₁₆H₂₅NO₂ · C₄H₄O₄) in the portion of Desvenlafaxine Fumarate taken:

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

r_U = peak response of desvenlafaxine from the Sample solution

r_S = peak response of desvenlafaxine from the Standard solution S

C_S = concentration of USP Desvenlafaxine Fumarate RS in the Standard solution (mg/mL) S

C_U = concentration of Desvenlafaxine Fumarate in the Sample solution (mg/mL)

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

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281): NMT 0.1%

4.2 ORGANIC IMPURITIES

Buffer, Solution A, Solution B, Diluent, and Chromatographic system: Proceed as directed in the Assay.

Mobile phase: See Table 2.

Table 2

System suitability solution: 1 mg/mL of USP Desvenlafaxine Fumarate RS and 0.0015 mg/mL of USP Desvenlafaxine Related Compound BRS in Diluent

Sensitivity solution: 0.5 µg/mL of USP Desvenlafaxine Fumarate RS, equivalent to 0.3 µg/mL of desvenlafaxine, in Diluent

Standard solution: 0.001 mg/mL of USP Desvenlafaxine Fumarate RS, equivalent to 0.0006 mg/mL of desvenlafaxine, in Diluent

Sample solution: 1 mg/mL of Desvenlafaxine Fumarate in Diluent

4.2.1 System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

[NOTE-See Table 3 for the relative retention times.]

4.2.2 Suitability requirements

Resolution: NLT 0.8 between desvenlafaxine related compound B and desvenlafaxine, System suitability solution

Relative standard deviation: NMT 10.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

4.2.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Desvenlafaxine Fumarate taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of desvenlafaxine fumarate from the Standard solution s

C_S = concentration of USP Desvenlafaxine Fumarate RS in the Standard solution (mg/mL)

C_U = concentration of Desvenlafaxine Fumarate in the Sample solution (mg/mL)

F = relative response factor (see Table 3)

Acceptance criteria: See Table 3. The reporting threshold is 0.05%.

Table 3

^a Included for identification only. This peak is due to the fumarate counterion; hence it is not an impurity.

^b 1-(1-[4-(Benzyloxy)phenyl]-2-(dimethylamino) ethyl cyclohexan-1-ol.

5 SPECIFIC TESTS

OPTICAL ROTATION (781S), Procedures, Specific Rotation

Sample solution: 10 mg/mL of Desvenlafaxine Fumarate in methanol

Acceptance criteria: -0.5° to 0.5° on the anhydrous basis

PH (791).

Sample solution: 10 mg/mL of Desvenlafaxine Fumarate in water

Acceptance criteria: 3.0-5.0

WATER DETERMINATION (921), Method I: 4.0%-6.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers.

USP REFERENCE STANDARDS (11)

USP Desvenlafaxine Fumarate RS

USP Desvenlafaxine Related Compound B RS

4-[1-(1-Hydroxycyclohexyl)-2-(methylamino)ethyl]phenol.

C₁₅H₂₃NO₂             249.35