Desvenlafaxine

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             263.38

4-[2-(Dimethylamino)-1-(1-hydroxycyclohexyl)ethyl]phenol;

1-[2-(Dimethylamino)-1-(4-hydroxyphenyl)ethyl]cyclohexanol CAS RN: 93413-62-8; UNII: NG99554ANW.

1 DEFINITION

Desvenlafaxine contains NLT 98.0% and NMT 102.0% of desvenlafaxine (C₁₆H₂₅NO₂), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

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

3.1 PROCEDURE

Solution A: 4 g/L of ammonium bicarbonate in water adjusted with phosphoric acid to a pH of 7.0

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (90:10)

System suitability solution: 0.701 mg/mL of USP Desvenlafaxine RS, 0.001 mg/mL of USP Desvenlafaxine Related Compound A RS, and 0.0035 mg/mL of USP Venlafaxine Hydrochloride RS in Diluent

Standard solution: 0.7 mg/mL of USP Desvenlafaxine RS in Diluent

Sample solution: 0.7 mg/mL of Desvenlafaxine in Diluent

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 226 nm

Column: 4.6-mm x 25-cm; 5.0-µm packing 11.

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 10 µL

3.1.2 System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 2 for the relative retention times.]

3.1.3 Suitability requirements

Resolution: NLT 3.5 between desvenlafaxine related compound A and venlafaxine, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

3.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of desvenlafaxine (C₂H₂NO₂) in the portion of Desvenlafaxine taken: 16 25

                Result = (r_U/r_S) x (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 Desvenlafaxine RS in the Standard solution (mg/mL)

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

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

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281): NMT 0.20%

4.2 ORGANIC IMPURITIES

Mobile phase, Diluent, System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.0007 mg/mL of USP Desvenlafaxine RS, 0.001 mg/mL of USP Desvenlafaxine Related Compound A. RS, and 0.0011 mg/mL of USP Venlafaxine Hydrochloride RS (equivalent to 0.001 mg/mL of venlafaxine) in Diluent

Sensitivity solution: 0.35 µg/mL of USP Desvenlafaxine RS from the Standard solution in Diluent

4.2.1 System suitability

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

[NOTE-See Table 2 for the relative retention times.]

4.2.2 Suitability requirements

Resolution: NLT 3.5 between desvenlafaxine related compound A and venlafaxine, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

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

4.2.3 Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of desvenlafaxine related compound A in the portion of Desvenlafaxine taken:

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

r_U = peak response of desvenlafaxine related compound A from the Sample solution

r_S = peak response of desvenlafaxine related compound A from the Standard solution

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

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

Calculate the percentage of venlafaxine in the portion of Desvenlafaxine taken:

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

r_U = peak response of venlafaxine 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 Desvenlafaxine in the Sample solution (mg/mL)

M_r1 = molecular weight of venlafaxine, 277.40

M_r2 = molecular weight of venlafaxine hydrochloride, 313.86

Calculate the percentage of any individual impurity in the portion of Desvenlafaxine taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of desvenlafaxine from the Standard solution

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

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

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

5 SPECIFIC TESTS

LOSS ON DRYING (731)

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 0.50%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

USP REFERENCE STANDARDS (11)

USP Desvenlafaxine RS

USP Desvenlafaxine Related Compound A RS

4-[1-(Cyclohex-1-en-1-yl)-2-(dimethylamino) ethylphenol.

C₁₆H₂₃NO         245.37

USP Venlafaxine Hydrochloride RS