Atovaquone

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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Atovaquone

C₂₂H₁₉ClO₃ 366.84

1,4-Naphthalenedione, 2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-, trans-;

2-[trans-4-(p-Chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone

CAS RN®: 95233-18-4; UNII: Y883P1Z2LT.

1 DEFINITION

Atovaquone contains NLT 97.5% and NMT 101.5% of atovaquone (C₂₂H₁₉ClO₃), calculated on the anhydrous and organic solvent-free basis.

2 IDENTIFICATION

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

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

Mobile phase: Acetonitrile, methanol, water, and phosphoric acid (525:175:300:5)

Diluent: Acetonitrile and water (80:20)

System suitability solution: 0.25 mg/mL of USP Atovaquone RS and 0.02 mg/mL of USP Atovaquone Related Compound A RS in Diluent. Store in a low-actinic glass container.

Standard solution: 0.25 mg/mL of USP Atovaquone RS in Diluent

Sample solution: 0.25 mg/mL of Atovaquone in Diluent. Use a low-actinic volumetric flask.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 25-cm; packing L1

Flow rate: 3 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for atovaquone related compound A and atovaquone are about 0.85 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 4 between atovaquone related compound A and atovaquone, System suitability solution

Column efficiency: NLT 9000 theoretical plates, Standard solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 2%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of atovaquone (C₂₂H₁₉ClO₃) in the portion of Atovaquone 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 Atovaquone RS in the Standard solution (mg/mL)

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

Acceptance criteria: 97.5%–101.5% on the anhydrous and organic solvent-free basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Mobile phase, Diluent, System suitability solution, Standard solution, Sample solution, Chromatographic system and System suitability: Proceed as directed in the Assay.

Analysis

Sample: Sample solution

Calculate the percentage of atovaquone related compounds in the portion of Atovaquone taken:

Result = (r_U / r_T) × 100

r_U = peak response of each impurity from the Sample solution

r_T= sum of all the peak responses from the Sample solution

Acceptance criteria: See Table 1

ᵃ trans-2-[4-(4-Chlorophenyl)cyclohexyl]-1-oxo-1H-indene-3-carboxylic acid.

ᵇ (RS)-2-[4-(4-Chlorophenyl)cyclohex-3-enyl]-3-hydroxy-1,4-naphthoquinone.

ᶜ trans-2-[4-(4-Chlorophenyl)cyclohexyl]-3-methoxy-1,4-naphthoquinone.

5 SPECIFIC TESTS

Water Determination, Method I〈921〉: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

USP Reference Standards 〈11〉

USP Atovaquone RS

USP Atovaquone Related Compound A RS

cis-2-[4-(4-Chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone.

C₂₂H₁₉ClO₃ 366.84