Etravirine

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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Benzonitrile, 4-[[6-amino-5-bromo-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3,5-dimethyl-;

4-({6-Amino-5-bromo-2-[(4-cyanophenyl)amino]-4-pyrimidinyl}oxy)-3,5-dimethyl-benzonitrile CAS RN_®: 269055-15-4; UNII: 0C50HW4FO1.

1 DEFINITION

Etravirine contains NLT 98.0% and NMT 102.0% of etravirine (C₂₀H₁₅BrN₆O), calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K or 197A

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 etravirine from light.

Buffer: 10 mM ammonium formate in water

Diluent: Acetonitrile and Buffer (10:9, v/v)

Solution A: 50 mM formic acid in Buffer

Solution B: Acetonitrile

Solution C: Methanol

Mobile phase: See Table 1

Standard stock solution: 2.0 mg/ml. of USP Etravirine RS in 1-methyl-2-pyrrolidone

Standard solution: 0.10 mg/mL of USP Etravirine RS from the Standard stock solution in Diluent

Sample stock solution: 2.0 mg/mL of Etravirine in 1 methyl-2-pyrrolidone

Sample solution: 0.10 mg/mL of Etravirine from the Sample stock solution in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 310 nm

Column: 3.0-mm × 15-cm; 5-μm packing L1

Column temperature: 35°

Flow rate: 0.6 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of etravirine (C₂₀H₁₅BrN₆O) in the portion of Etravirine taken:

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

r_U = peak response of etravirine from the Sample solution

r_S = peak response of etravirine from the Standard solution

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

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

Acceptance criteria: 98.0%-102.0%, on the anhydrous and solvent-free basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

ORGANIC IMPURITIES

Protect solutions containing etravirine from light.

Buffer, Diluent, Solution A, Solution B, Solution C, Mobile phase, Standard stock solution, Standard solution, Sample stock solution,

Sample solution, and Chromatographic system: Proceed as directed in the Assay

System suitability solution: 0.10 mg/mL of USP Etravirine System Suitability Mixture RS prepared as follows. Transfer a suitable amount of USP Etravirine System Suitability Mixture RS to a suitable volumetric flask and dissolve in 10% of the total volume of 1-methyl-2-ovrrolidone Dilute with Diluent to volume.

Sensitivity solution: 0.05 µg/mL of USP Etravirine RS from the Standard solution in Diluent

System suitability

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

NOTE-The relative retention times for etravirine amino analog and desbromoetravirine in relation to etravirine are 0.66 and 0.73, respectively.)

Suitability requirements

Resolution: NLT 4.3 between etravirine amino analog and desbromoetravirine, System suitability solution

Relative standard deviation: NMT 0.73%, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response of any individual impurity from the Sample solution

r_S = peak response of etravirine from the Standard solution

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

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

F = relative response factor (see Table 2)

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

^a 4-[(4-Amino-5-bromo-6-chloropyrimidin-2-yl)amino]benzonitrile.

For peak identification purpose. If present, these impurities are covered under acceptance criteria for any individual unspecified impurity.

^b 4-(16-Amino-2-(4-cyanophenyl)amino)pyrimidin-4-yl)oxy)-3,5-dimethylbenzonitrile.

^c 4-(15-Bromo-6-(4-cyano-2,6-dimethylphenoxy)-2-[(4-cyanophenyl)amino]pyrimidin-4-yll (methyl)amino)butanamide.

^d 4,4-15-Bromo-2-[(4-cyanophenyl)amino]pyrimidine-4,6-diyi bis(oxy) bis(3,5-dimethylbenzonitrile).

5 SPECIFIC TESTS

WATER DETERMINATION (921), Method. Method la: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers, and store at room temperature.