Efavirenz Capsules

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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1 DEFINITION

Efavirenz Capsules contain NLT 92.0% and NMT 108.0% of the labeled amount of efavirenz (C₁₄H₉ClF₃NO₂).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

Sample solution: Dissolve the contents of 1 Capsule in about 5 mL of acetonitrile by mixing on a vortex mixer. Allow to settle, remove about 3mL of the solution, and centrifuge for about 5 min. Transfer 1–2 mL of supernatant to a clean suitable container, and evaporate to dryness under nitrogen. Mix 0.5–1 mg of the powder with 200 mg of potassium bromide.

Change to read:

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U (CN 1-May-2020)

Solvent: Acetonitrile

Standard solution: 10 μg/mL in Solvent

Sample solution: Dissolve the contents of 1 Capsule in about 40 mL of Solvent by shaking for about 30 min. Pass through a suitable nylon or PVDF membrane filter, discarding the first 2 mL of filtrate, and dilute a portion with acetonitrile to a concentration of 10 μg/mL of efavirenz.

Acceptance criteria: The UV absorption spectrum of the Sample solution exhibits maxima and minima at the same wavelengths as does the

Standard solution.

3 ASSAY

Procedure

Diluent: Acetonitrile and water (1:1)

Solution A: Methanol, tri

uoroacetic acid, and water (1:0.005:9). [Note—Use only freshly-opened tri

uoroacetic acid, ≤6 months.]

Solution B: Methanol, trifluoroacetic acid, and water (9:0.005:1). [Note—Use only freshly-opened trifluoroacetic acid, ≤6 months.]

Mobile phase: See the gradient table below.

Standard solution 1: 0.2 mg/mL of USP Efavirenz Related Compound B RS in Diluent

Standard solution 2: 5 mg/mL of USP Efavirenz RS in acetonitrile. [Note—Sonicate to dissolve before diluting to final volume.]

Standard solution: 250 μg/mL of USP Efavirenz RS and 1 μg/mL of USP Efavirenz Related Compound B RS in Diluent prepared from Standard solution 2 and Standard solution 1, respectively. [Note—Store protected from light. For the HPLC analysis, it is recommended to use polypropylene vials, because degradation has been noted with certain brands made of glass.]

Sample stock solution: Transfer the contents of NLT 10 Capsules to a suitable container, and extract the contents in acetonitrile by mixing for about 30 min to obtain a quantitative solution equivalent to about 5 mg/mL of efavirenz. [Note—Store protected from light.]

Sample solution: Filter a portion of the Sample stock solution, and dilute the filtrate with Diluent to obtain a solution of about 250 μg/mL of efavirenz. [Note—Store protected from light. For the HPLC analysis, it is recommended to use polypropylene vials, because degradation has been noted with certain brands made of glass.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 250 nm

Column: 4.6-mm × 15-cm; packing L10

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection size: 35 μL

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 1.2 between efavirenz related compound B and efavirenz

Relative standard deviation: NMT 2.0% for efavirenz

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of efavirenz (C₁₄H₉ClF₃NO₂) in the portion of Capsules taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of efavirenz from the Sample solution

r_S = peak response of efavirenz from the Standard solution

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

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

Acceptance criteria: 92.0%–108.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: 1.0% (w/v) sodium lauryl sulfate in water; 900 mL. [Note—Do not deaerate.]

Apparatus 2: 50 rpm, with helix sinker

Time: 45 min

Standard solution: (L/900) mg/mL of USP Efavirenz RS in Medium, where L is the Capsule label claim in mg. A small volume of methanol, NMT 10% of the final volume, could be used to solubilize efavirenz. Dilute this solution with Medium to obtain a final concentration of about 0.01 mg/mL for Capsules labeled to contain 50 mg, or about 0.02 mg/mL for Capsules labeled to contain 100 mg or 200 mg.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size, and dilute with Medium to obtain a theoretical concentration similar to the Standard solution, assuming complete dissolution of the Capsule label claim.

Analytical wavelength: UV 247 nm

Cell: 1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of efavirenz dissolved:

Result = (A_U/A_S) × (C_S/L) × D × V × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

L = label claim (mg/Capsule)

D = dilution factor of the Sample solution

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of efavirenz is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

Procedure for content uniformity

Standard solution: 10 μg/mL of USP Efavirenz RS in acetonitrile

Sample solution: Transfer the contents of 1 Capsule into a suitable container, and dissolve in 40.0 mL of acetonitrile. Shake for about 30 min and pass through a suitable nylon or PVDF membrane filter. Dilute a portion of the filtrate to an efavirenz concentration of about 10 μg/mL.

Spectrometric conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV absorption spectroscopy

Analytical wavelength: UV 246 nm

Cell: 1 cm

Blank: Acetonitrile

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of efavirenz (C₁₄H₉ClF₃NO₂) in the portion of Capsules taken:

Result = (A_U/A_S) × (C_S/L) × V × D × 100

A_U = absorbance of efavirenz from the Sample solution

A_S = absorbance of efavirenz from the Standard solution

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

L = label claim (mg/Capsule)

V = volume of the Sample solution

D = dilution factor of the Sample solution

5 IMPURITIES

Organic Impurities

Procedure

Diluent, Solution A, Solution B, Sample solution, and Chromatographic system: Prepare as directed in the Assay.

System suitability solution: Use the Standard solution prepared as directed in the Assay.

Standard solution: 1.25 μg/mL of USP Efavirenz RS and 0.005 μg/mL of USP Efavirenz Related Compound B RS in Diluent from the System suitability solution

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.2 between efavirenz related compound B and efavirenz, System suitability solution

Relative standard deviation: NMT 5.0% for efavirenz, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response of any individual impurity (degradation product) from the Sample solution

r_S = peak response of efavirenz from the Standard solution

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

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

F = relative response factor (see Impurity Table 1)

Acceptance criteria

Individual impurities: See Impurity Table 1. [Note—Disregard any peak less than 0.05%.]

Total impurities: NMT 0.50%. [Note—Include only the degradation products in the calculation of the total impurities.]

Impurity Table 1

* For information purposes only. These are process impurities monitored in the drug substance and are not included in the total impurities.

^a (S)-2-(2-Amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-triuorobut-3-yn-2-ol.

^b (S,E)-6-Chloro-4-(2-cyclopropylvinyl)-4-(triuoromethyl)-2H-3,1-benzoxazin-2-one.

^c (S,E)-6-Chloro-4-(pent-3-en-1-ynyl)-4-(triuoromethyl)-2H-3,1-benzoxazin-2-one.

^d (S,Z)-6-Chloro-4-(pent-3-en-1-ynyl)-4-(triuoromethyl)-2H-3,1-benzoxazin-2-one.

^e (S)-6-Chloro-4-(3-methylbut-3-en-1-ynyl)-4-(triuoromethyl)-2H-3,1-benzoxazin-2-one.

^f (S)-6-Chloro-4-(pent-1-ynyl)-4-(triuoromethyl)-2H-3,1-benzoxazin-2-one.

^g (S)-6-Chloro-4-{[(2RS,2RS)-2-methylcyclopropyl]ethynyl}-4-(triuoromethyl)-2H-3,1-benzoxazin-2-one.

^h (S)-Methyl 4-chloro-2-(4-cyclopropyl-1,1,1-triuoro-2-hydroxybut-3-yn-2-yl)phenylcarbamate.

ⁱ (S)-6-Chloro-4-(cyclopropylethynyl)-1-(4-methoxybenzyl)-4-(triuoromethyl)-2H-3,1-benzoxazin-2-one.

^j (S)-N-[4-Chloro-2-(4-cyclopropyl-1,1,1-triuoro-2-hydroxybut-3-yn-2-yl)phenyl]-4-methoxybenzamide.

^k 6-Chloro-2-cyclopropyl-4-(triuoromethyl)quinoline.

^l (S)-Ethyl 4-chloro-2-(4-cyclopropyl-1,1,1-triuoro-2-hydroxybut-3-yn-2-yl)phenylcarbamate.

^m (S)-Ethyl 4-chloro-2-[4-cyclopropyl-2-(ethoxycarbonyloxy)-1,1,1-triuorobut-3-yn-2-yl]phenylcarbamate.

ⁿ Ethyl 5-chloro-2-cyclobutenyl-3-(triuoromethyl)-1H-indole-1-carboxylate.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Store in well-closed containers at controlled room temperature.

USP Reference Standards 〈11〉

USP Efavirenz RS

USP Efavirenz Related Compound B RS

(S,E)-6-Chloro-4-(2-cyclopropylvinyl)-4-(triuoromethyl)-2H-3,1-benzoxazin-2-one.

C₁₄H₁₁ClF₃NO₂ 317.69