Atovaquone Oral Suspension

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 Oral Suspension

1 DEFINITION

Atovaquone Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of atovaquone (C₂₂H₁₉ClO₃).

2 IDENTIFICATION

Change to read:

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

Medium: Methanol and water (1:1)

Standard solution: Dilute 5 mL of Standard solution from the Assay with Medium to 50 mL.

Sample solution: Dilute 5 mL of Sample solution from the Assay with Medium to 50 mL.

Acceptance criteria: Meets 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

Mobile phase: Acetonitrile, methanol, water, and phosphoric acid (480:160:360:5)

System suitability solution: 0.09 mg/mL of USP Atovaquone RS and 0.01 mg/mL of USP Atovaquone Related Compound A RS in 0.1 M methanolic sodium hydroxide. Store in a low-actinic glass container.

Standard stock solution: 3 mg/mL of USP Atovaquone RS in a low-actinic, appropriately sized volumetric flask. Add 20% water and 60% 0.1 M methanolic sodium hydroxide. Sonicate for 5 min or until the material has dissolved. Allow to cool, and dilute with 0.1 M methanolic sodium hydroxide to volume.

Standard solution: 0.09 mg/mL of USP Atovaquone RS from Standard stock solution. Transfer to an appropriately sized, low-actinic volumetric flask in a mixture of methanol and water (1:1). Minimize exposure of this solution to light.

Sample stock solution: Nominally 3 mg/mL from a known volume of well-mixed Oral Suspension NLT 750 mg of atovaquone prepared as follows. In an appropriately sized, low-actinic volumetric flask, add 20% volume of water, swirl for 5 min, add 60% volume of 0.1 M methanolic sodium hydroxide, and sonicate for 15 min. Allow to cool, and dilute with 0.1 M methanolic sodium hydroxide to volume. Immediately filter a 20-mL portion, discarding the first 5 mL of the filtrate.

Sample solution: 0.09 mg/mL of atovaquone from the clear filtrate of the Sample stock solution. Transfer to an appropriately sized, low-actinic volumetric flask, and dilute with a mixture of methanol and water (1:1) to volume. Minimize exposure of this solution to light.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 12.5-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 0.86 and 1.0, respectively.]

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of atovaquone (C₂₂H₁₉ClO₃) in the portion of Oral Suspension taken:

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

r_U = peak response of atovaquone from the Sample solution

r_S= peak response of atovaquone from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

Atovaquone-Oral-Suspension-ttt

4 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements for oral suspension packaged in single-unit containers

Deliverable Volume 〈698〉: Meets the requirements for oral suspension packaged in multiple-unit containers

5 IMPURITIES

Organic Impurities

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

Analysis

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

Using the chromatograms of the System suitability solution and the Sample solution, calculate the percentage of atovaquone related compounds in the portion of Oral Suspension taken:

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

r_U = individual peak response of an atovaquone related compound, if any, from the Sample solution

r_S= peak response of atovaquone from the Standard solution

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

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

F = relative response factor of an individual atovaquone related compound relative to the response of atovaquone (see Table 1)

Acceptance criteria: See Table 1.

ᵃ Disregard any peak having a relative retention time of 0.3, which is due to photodegradation during preparation of the Sample solution.

6 SPECIFIC TESTS

pH 〈791〉: 3.5–7.0

Sedimentation (for oral suspension packaged in multiple-unit containers)

Analysis: Transfer 50 mL of well-mixed Oral Suspension to a glass-stoppered graduated cylinder, and allow to stand for 16 h. Measure the volume, if any, of clear liquid observed in the cylinder.

Acceptance criteria: NMT 1 mL of clear liquid

7 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