Sorafenib Tosylate

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

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

DOWNLOAD PDF HERE

1 DEFINITION

Sorafenib Tosylate contains NLT 97.0% and NMT 102.0% of sorafenib tosylate (C₂₁H₁₆ClF₃N₄O₃ · C₇H₈O₃S), calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉, Infrared Spectroscopy:  [NOTE—Methods described in 197K or 197A may be used.]

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

Protect solutions containing sorafenib tosylate from light. Do not sonicate.

Solution A: 1 mL of phosphoric acid and 1 g of potassium phosphate, monobasic in 1 L of water

Solution B: Absolute alcohol and acetonitrile (4:6)

Mobile phase: See Table 1. Return to original conditions, and equilibrate the system for 10 min.

Table 1

Diluent: Dimethyl sulfoxide, acetonitrile, and phosphoric acid (85:15:0.1) Standard solution: 1.0 mg/mL of USP Sorafenib Tosylate RS in Diluent Sample solution: 1.0 mg/mL of Sorafenib Tosylate in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 235 nm

Column: 2.1-mm × 15-cm; 3.5-µm packing L7

Column temperature: 75°

Flow rate: 0.6 mL/min

Injection volume: 3 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.6

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of sorafenib tosylate (C₂₁H₁₆ClF₃N₄O₃ · C₇H₈O₃S) in the portion of Sorafenib Tosylate 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 Sorafenib Tosylate RS in the Standard solution (mg/mL)

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

Acceptance criteria: 97.0%–102.0% on the anhydrous and solvent-free basis

4 IMPURITIES

ORGANIC IMPURITIES

Protect solutions containing sorafenib tosylate from light. Do not sonicate.

Solution A, Solution B, Mobile phase, Diluent, Standard solution, and Sample solution: Prepare as directed in the Assay.

System suitability solution: 3.0 µg/mL of USP Sorafenib Related Compound H RS in Standard solution. It contains 3.0 µg/mL of USP Sorafenib Related Compound H RS and 1.0 mg/mL of USP Sorafenib Tosylate RS in Diluent.

Sensitivity solution: 0.5 µg/mL of USP Sorafenib Tosylate RS in Diluent, from Standard solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 235 nm

Column: 2.1-mm × 15-cm; 3.5-µm packing L7

Column temperature: 75°

Flow rate: 0.6 mL/min

Injection volume: 3 µL

System suitability

Samples: System suitability solution and Sensitivity solution

Suitability requirements

Resolution: NLT 2.2 between the sorafenib related compound H and sorafenib peaks, System suitability solution Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Sorafenib Tosylate taken:

Result = [r_U × (1/F)]/{Σ[r_U × (1/F)] + r_S} × 100

r_U = peak response of each impurity from the Sample solution

F = relative response factor (see Table 2)

r_S = peak response of sorafenib from the Sample solution

Acceptance criteria: See Table 2. The reporting threshold is 0.05%. Disregard toluenesulphonic acid at a relative retention time of 0.07. [NOTE—Toluenesulphonic acid is the counter ion of sorafenib and is present in the chromatogram of the Sample solution.]

Table 2

^a 4-(4-Aminophenoxy)-N-methylpicolinamide.

^b  4-(4-Formamidophenoxy)-N-methylpicolinamide.

^c 4-Chloro-3-(trifluoromethyl)aniline.

^d  Isopropyl {4-[2-(methylcarbamoyl)pyridin-4-yl]oxyphenyl}carbamate.

^e N,N’-Bis{4-[2-(N-methylcarbamoyl)-4-pyridyloxy]phenyl}urea.

^f  N-Methyl-4-{4-[3-(3-trifluoromethylphenyl)ureido]phenoxy}picolinamide.

5 SPECIFIC TESTS

WATER DETERMINATION 〈921〉 , Method I

Sample: 200 mg

Analysis: Evaporation technique Temperature: 150°

Heating time: 3 min Carrier gas: Nitrogen Flow rate: 70 mL/min

Reagent: Hydranal Coulomat AG, or Hydranal Coulomat AK or equivalent Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, and protect from light. Store at room temperature.

USP REFERENCE STANDARDS 〈11〉

USP Sorafenib Tosylate RS

USP Sorafenib Related Compound H RS

4-(4-{3-[2-Chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N-methylpicolinamide.

C₂₁H₁₆ClF₃N₄O₃           464.83 (USP 1-May-2021)