Efavirenz Tablets

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

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

Sample solution: Completely remove the coating film from a Tablet using a mortar and pestle to crack the Tablet, grind the contents into fine powder, and place the powder into a suitable container. Dissolve the contents in about 5 mL of acetonitrile by mixing on a vortex mixer.

Allow to settle, remove about 3 mL of the solution, and centrifuge for about 5 min using a suitable container. 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.

Acceptance criteria: Meet the requirements

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

Diluent: Acetonitrile and water (500:500)

Solution A: Methanol, trifluoroacetic acid, and water (100:0.5:900)

Solution B: Methanol, trifluoroacetic acid, and water (900:0.5:100)

Mobile phase: See Table 1.

Table 1

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

Standard stock solution 2: 5 mg/mL of USP Efavirenz RS in Diluent. 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 stock 2 and Standard stock solution 1, respectively. Store protected from light. For the HPLC analysis, it is recommended to use polypropylene vials, because degradation may occur with glass containers.

Sample stock solution: Nominally, 12 mg/mL of efavirenz in Diluent prepared as follows. Transfer NLT 10 Tablets to a suitable container, and extract the contents in Diluent by mixing for about 90 min. Store protected from light.

Sample solution: Nominally, 240 μg/mL of efavirenz in Diluent prepared as follows. Filter a portion of the Sample stock solution, and dilute the filtrate with Diluent. Store protected from light. For the HPLC analysis, it is recommended to use polypropylene vials, because degradation may occur with glass containers.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 250 nm

Column: 4.6-mm × 15-cm; 5-μm packing L10

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 35 μL

System suitability

Sample: Standard solution

[Note—The typical retention times for efavirenz related compound B and efavirenz are 0.9 and 1.0, respectively.]

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 the labeled amount of efavirenz (C₁₄H₉ClF₃NO₂) in the portion of Tablets 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: 2.0% (w/v) sodium lauryl sulfate in water; 1000 mL. Do not deaerate.

Apparatus 2: 50 rpm, with helix sinker. In addition, paddle and shaft must be composed of stainless steel and not coated with Teflon or other material. Also, all sampling devices and dissolution vessels must be washed with methanol or Ethanol followed by a water wash.

Time: 30 min

Standard solution: (L/1000) mg/mL of USP Efavirenz RS in Medium, where L is the Tablet label claim in mg. A small volume of methanol, NMT 1% of the final volume, could be used to solubilize efavirenz. Dilute this solution with Medium to obtain a final concentration of about 0.012 mg/mL.

Sample solution: Pass a portion of the solution under test through a suitable polyethylene filter, and dilute with Medium to obtain a concentration similar to the Standard solution, assuming complete dissolution of the Tablet label claim.

Instrumental conditions

Analytical wavelength: UV 247 nm

Cell: 1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of efavirenz (C₁₄H₉ClF₃NO₂) dissolved:

Result = (A_U/A_S) × C_S × V × D × (1/L) × 100 

A_U= absorbance of the Sample solution

A_S= absorbance of the Standard solution

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

V = volume of Medium, 1000 mL

D = dilution for the Sample solution

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of efavirenz (C₁₄H₉ClF₃NO₂) is dissolved.

Change to read:

Uniformity of Dosage Units 〈905〉:Meet the requirements (CN 1-Aug-2023)

Procedure for content uniformity

Diluent: Acetonitrile and water (50:50)

Standard solution: 12 μg/mL of USP Efavirenz RS in Diluent

Sample solution: Transfer NLT 10 Tablets into separate and suitable containers, and dissolve in 250 mL of Diluent. Stir for about 90 min, and centrifuge a portion of each solution for 10 min. Pass about 10 mL through a suitable nylon or PVDF membrane filter. Immediately dilute a portion of the filtrate to an efavirenz concentration of about 12 μg/mL.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: UV 246 nm

Cell: 1 cm

Blank: Diluent

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of efavirenz (C₁₄H₉ClF₃NO₂) in each Tablet 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/Tablet)

V = volume of the Sample solution (mL)

D = dilution factor of the Sample solution

 (CN 1-Aug-2023)

5 IMPURITIES

Organic Impurities

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 degradation product in the Tablet 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 Table 2)

Acceptance criteria: See Table 2.

Table 2

^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 For information purposes only. These are process impurities monitored in the drug substance and are not included in the total impurities. Include only the degradation products in the calculation of the total impurities.

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

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

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

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

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

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

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

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

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

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

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

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

^p Disregard any peak less than 0.05%.

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.

C_¹⁴H_¹¹ClF_²NO_² 317.69