Desvenlafaxine Succinate

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 · C₄H6O₄ · H₂O          399.48

C₁₆H₂₅NO₂ · C₄H6O₄        381.47

Butanedioic acid, compound with 4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl)ethylphenol (1:1), monohydrate;

1-[2-(Dimethylamino)-1-(4-hydroxyphenyl)ethyl] cyclohexanol hydrogen butanedioate monohydrate CAS RN^®: 386750-22-7; UNII: ZB22ENFOXR.

Anhydrous CAS RN^®: 448904-47-0; UNII: H9E1T0B190.

1 DEFINITION

Desvenlafaxine Succinate contains NLT 98.0% and NMT 102.0% of desvenlafaxine succinate (C₁₆H₂₅NO₂ · C₄H6O₄), 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 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

Buffer: 2.7 g/L of monobasic potassium phosphate in water

Solution A: Acetonitrile and Buffer (18:82)

Mobile phase: To each liter of Solution A, add 5.4 mL of triethylamine, and adjust with phosphoric acid to a pH of 4.0.

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

Sample solution: 0.05 mg/mL of Desvenlafaxine Succinate in Mobile phase. Sonication may be used to promote dissolution.

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm x 25-cm; 5-µm packing 11

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: NLT 1.6 times the retention time of desvenlafaxine

3.1.2 System suitability

Sample: Standard solution

3.1.3 Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 0.73%

3.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of desvenlafaxine succinate (C₁₆H₂₅NO₂ · C₄H6O₄) in the portion of Desvenlafaxine Succinate taken:

                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 S

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

C_U = concentration of Desvenlafaxine Succinate 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: 7.1 g/L of anhydrous dibasic sodium phosphate in water

Solution A: Acetonitrile and Buffer (10:90); adjusted with phosphoric acid to a pH of 3.0

Solution B: Acetonitrile and Buffer (60:40); adjusted with phosphoric acid to a pH of 3.0

Mobile phase: See Table 1.

Table 1

System suitability solution: 1 mg/mL of USP Desvenlafaxine Succinate RS and 0.0015 mg/mL of USP Desvenlafaxine Related Compound BRS in Solution A. Sonication may be used to promote dissolution.

Standard solution: 0.001 mg/mL of USP Desvenlafaxine Succinate RS, equivalent to 0.0007 mg/mL of desvenlafaxine, in Solution A.

Sonication may be used to promote dissolution.

Sensitivity solution: 0.5 µg/mL of USP Desvenlafaxine Succinate RS, equivalent to 0.35 µg/mL of desvenlafaxine, from the Standard solution in Solution A

Sample solution: 1 mg/mL of Desvenlafaxine Succinate in Solution A

4.2.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm x 25-cm; 3-µm packing L1

4.2.2 Temperatures

Autosampler: 10°

Column: 50°

Flow rate: 1.5 mL/min

Injection volume: 20 µL

4.2.3 System suitability

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

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

4.2.4 Suitability requirements

Resolution: NLT 1.5 between desvenlafaxine related compound B and desvenlafaxine, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

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

4.2.5 Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of desvenlafaxine succinate from the Standard solution 

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

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

F = relative response factor (see Table 2)

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

Table 2

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

^b 4-[2-(Dimethylamino)ethyl]phenol.

^c 4-[2-Amino-1-(1-hydroxycyclohexyl)ethyl]phenol.

^d 4-[1-(Cyclohex-1-en-1-yl)-2-(dimethylamino) ethyl]phenol.

^e 1-[2-(Dimethylamino)-1-(4-methoxyphenyl)ethyl] cyclohexan-1-ol.

5 SPECIFIC TESTS

WATER DETERMINATION (921), Method /: 4.0%-5.2%

6 ADDITIONAL REQUIREMENTS

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

USP REFERENCE STANDARDS (11)

USP Desvenlafaxine Succinate RS

USP Desvenlafaxine Related Compound B RS

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

C₁₅H₂₃NO₂           249.35