Hydroxychloroquine Sulfate Compounded 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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1 DEFINITION

Hydroxychloroquine Sulfate Compounded Oral Suspension contains NLT 93.0% and NMT 107.0% of the labeled amount of hydroxychloroquine sulfate (C₁₈H₂₆ClN₃O . H₂SO₄).

Prepare Hydroxychloroquine Sulfate Compounded Oral Suspension 25 mg/mL as follows (see Pharmaceutical Compounding-Nonsterile Preparations 〈795〉).

Formulation using Ora-Plus and Ora-Sweet SF

ᵃ Hydroxychloroquine sulfate 200 mg tablets, Sandoz Inc., Princeton, NJ.

ᵇ Perrigo, Allegan, MI.

Place the Hydroxychloroquine Sulfate tablets or powder in a suitable container. If using tablets, add a small amount of Vehicle to cover the tablets and allow to soak for 15 min. Mix well with a sufficient amount of Vehicle to form a smooth paste. Add a sufficient amount of Vehicle to make the contents pourable. Transfer the contents stepwise and quantitatively to a calibrated container using the remainder of the Vehicle. Add a sufficient amount of Vehicle to bring to final volume. Shake to mix well.

ᵃ PCCA, Houston, TX.

Place the Hydroxychloroquine Sulfate powder, Acesulfame Potassium, and Steviol Glycoside 95% in a suitable container and mix well. Add approximately 50 mL of PCCA SuspendIt and mix to form a smooth paste. Add a sufficient amount of PCCA SuspendIt to make the contents pourable. Transfer the contents stepwise and quantitatively to a calibrated container using the PCCA SuspendIt. Add the Flavor. Add sufficient Vehicle to bring to final volume and mix well.

2 ASSAY

2.1 FORMULATION IN ORA-PLUS AND ORA-SWEET SF

Solution A: Water and phosphoric acid (400:1); adjusted with 1 N sodium hydroxide to a pH of 3.0

Mobile phase: See Table 1.

Table 1

Standard solution: 0.1 mg/mL of hydroxychloroquine sulfate prepared from USP Hydroxychloroquine Sulfate RS in water. Sonicate for 5 min.

Sample solution: Transfer 1.0 mL of the Oral Suspension into a 250-mL volumetric flask. Add approximately 200 mL of water and sonicate for 15 min. Add water to volume. Centrifuge an aliquot for 10 min, and transfer the supernatant to an HPLC vial.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 340 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Temperatures

Autosampler: 4°

Column: 40°

Flow rate: 1.2 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

[Note-The retention time of hydroxychloroquine sulfate is about 4.5 min.]

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of hydroxychloroquine sulfate (C₁₈H₂₆ClN₃O . H₂SO₄) in the portion of Oral Suspension taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of hydroxychloroquine sulfate from the Sample solution

r_S = peak response of hydroxychloroquine sulfate from the Standard solution

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

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

Acceptance criteria: 93.0%–107.0%

2.2 FORMULATION IN PCCA SUSPENDIT

Solution A: 0.1% trifluoroacetic acid in water

Solution B: 0.1% trifluoroacetic acid in acetonitrile

Mobile phase: See Table 2.

Table 2

Standard solution: 0.1 mg/mL of hydroxychloroquine sulfate from USP Hydroxychloroquine Sulfate RS in water.

Sample solution: Transfer 1.0 mL of Oral Suspension into a 50-mL centrifuge tube. Add approximately 24 mL of water and vortex for 15 min. Sonicate for 2 min and vortex for 30 s. Centrifuge for 15 min at 6000 rpm. Transfer 1 mL of supernatant to a 10-mL volumetric flask and dilute with water to final volume. Transfer the solution to a micro-centrifuge tube and centrifuge for 10 min at 14,000 rpm. Transfer the solution to an HPLC vial.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 343 nm

Column: 2.1-mm × 5-cm; 1.7-µm packing L1

Temperatures

Autosampler: 25°

Column: 65°

Flow rate: 1 mL/min

Injection volume: 1 µL

System suitability

Sample: Standard solution

[Note-The retention time of hydroxychloroquine sulfate is about 1.2 min.]

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of hydroxychloroquine sulfate (C₁₈H₂₆ClN₃O . H₂SO₄) in the portion of Oral Suspension taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of hydroxychloroquine sulfate from the Sample solution

r_S = peak response of hydroxychloroquine sulfate from the Standard solution

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

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

Acceptance criteria: 93.0%-107.0%

3 SPECIFIC TESTS

APPEARANCE: Off-white to faint beige suspension

pH (791)

Formulation in Ora-Plus and Ora-Sweet SF

Oral suspension from Hydroxychloroquine Sulfate powder: 3.6-4.6

Oral suspension from Hydroxychloroquine Sulfate tablets: 4.4-5.4

Formulation in PCCA SuspendIt: 4.7-5.7

4 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Package in tight, light-resistant, plastic containers. Store in a refrigerator or at controlled room temperature.

BEYOND-USE DATE

Oral Suspension in Ora-Plus/Ora-Sweet SF: NMT 90 days after the date on which it was compounded when stored in a refrigerator or at controlled room temperature.

Oral Suspension in PCCA SuspendIt: NMT 180 days after the date on which it was compounded when stored in a refrigerator or at controlled room temperature. This formulation meets the requirements in Antimicrobial Effectiveness Testing 〈51〉.

LABELING: Label it to indicate that it is to be well shaken before use and to state the Beyond-Use Date.

USP REFERENCE STANDARDS (11)

USP Hydroxychloroquine Sulfate RS (USP 1-Aug-2023)