Hydroxychloroquine Sulfate 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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To view the Notice from the Expert Committee that posted in conjunction with this accelerated revision, please click www.uspnf.com/rb-hydroxychloroquine-sulfate-tabs-20231117.

1 DEFINITION

Hydroxychloroquine Sulfate Tablets contain NLT 93.0% and NMT 107.0% of the labeled amount of hydroxychloroquine sulfate (C₁₈H₂₆ClN₃O . H₂SO₄).

2 IDENTIFICATION

A. IDENTIFICATION-ORGANIC NITROGENOUS BASES (181)

Sample solution: Nominally 20 mg/mL of hydroxychloroquine sulfate in water prepared as follows. Triturate a quantity of finely powdered Tablets, equivalent to about 1 g of hydroxychloroquine sulfate, with 50 mL of water, and filter (retain the remainder of the filtrate for Identification B).

Acceptance criteria: The clear filtrate meets the requirements.

B. IDENTIFICATION TESTS-GENERAL (191), Chemical Identification Tests, Sulfate: The clear filtrate obtained from Identification A meets the
requirements.

C. 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

3.1 PROCEDURE

Solution A: Acetonitrile, water, and phosphoric acid (100:900:2)

Solution B: Acetonitrile, water, and phosphoric acid (800:200:1)

Mobile phase: Solution A and Solution B (97:3)

Standard solution: 0.01 mg/mL of USP Hydroxychloroquine Sulfate RS in Solution A prepared as follows. Transfer a suitable quantity of USP Hydroxychloroquine Sulfate RS to a suitable volumetric flask, and add Solution A to about 75% of the flask volume. Sonicate for NLT 5 min or until solids are dissolved. Dilute with Solution A to volume.

Sample stock solution: Nominally 1.0 mg/mL of hydroxychloroquine sulfate in Solution A prepared as follows. Transfer a portion of finely ground powder, from NLT 20 Tablets, equivalent to about 200 mg of hydroxychloroquine sulfate to a 200-mL volumetric flask and add Solution A to about 75% of the flask volume. Sonicate for NLT 10 min or until solids are dissolved. Dilute with Solution A to volume.

Sample solution: Nominally 0.01 mg/mL of hydroxychloroquine sulfate in Solution A from Sample stock solution. Pass through a suitable filter.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 2.0-mm × 10-cm; 2-µm packing L1

Column temperature: 35°

Flow rate: 0.8 mL/min

Injection volume: 3 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of hydroxychloroquine from the Sample solution

r_S = peak response of hydroxychloroquine 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%

4 PERFORMANCE TESTS

Change to read:

4.1 DISSOLUTION (711)

Test 1

Medium: Water; 900 mL, deaerated, if necessary (RB 1-Dec-2023)

Apparatus 2: 50 rpm

Time: 60 min

Standard solution: USP Hydroxychloroquine Sulfate RS in Medium

Sample solution: Pass a portion of the solution through a suitable filter. Dilute with Medium, if necessary.

Instrumental conditions

Mode: UV

Analytical wavelength: 343 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of hydroxychloroquine sulfate (C₁₈H₂₆ClN₃O . H₂SO₄) dissolved:

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

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

D = dilution factor of the Sample solution

V = volume of the Medium, 900 mL

L = label claim (mg/Tablet)

(RB 1-Dec-2023)

Tolerances: NLT 70% (Q) of the labeled amount of hydroxychloroquine sulfate (C₁₈H₂₆ClN₃O . H₂SO₄) is dissolved.

Test 2

If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: 0.1 N hydrochloric acid; 500 mL, deaerated

Apparatus 1: 100 rpm

Time: 30 min

Standard solution: 0.013 mg/mL USP Hydroxychloroquine Sulfate RS in Medium. Sonicate to dissolve, if necessary.

Sample solution: Pass a portion of the solution through a suitable filter of 0.45-µm pore size and discard NLT 5 mL of filtrate. Dilute with Medium to a concentration similar to the Standard solution.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 343 nm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of hydroxychloroquine sulfate (C₁₈H₂₆ClN₃O . H₂SO₄) dissolved:

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

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

D = dilution factor of the Sample solution

V = volume of the Medium, 500 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of hydroxychloroquine sulfate (C₁₈H₂₆ClN₃O . H₂SO₄) is dissolved.

Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Medium: 0.1 N hydrochloric acid; 500 mL, deaerated

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: (L/500) mg/mL of USP Hydroxychloroquine Sulfate RS in Medium, where L is the label claim of hydroxychloroquine sulfate in mg/Tablet. Sonicate to dissolve.

Sample solution: Pass a portion of the solution through a suitable filter of 0.45-µm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 343 nm

Cell path length: 0.2 mm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of hydroxychloroquine sulfate (C₁₈H₂₆ClN₃O . H₂SO₄) dissolved:

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

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

V = volume of the Medium, 500 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of hydroxychloroquine sulfate (C₁₈H₂₆ClN₃O . H₂SO₄) is dissolved. (RB 1-Dec-2023)

4.2 UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

5.1 ORGANIC IMPURITIES

Solution A: Acetonitrile, water, and phosphoric acid (100:900:2)

Solution B: Acetonitrile, water, and phosphoric acid (800:200:1)

Mobile phase: See Table 1.

Table 1

Standard stock solution: Use the Standard solution from the Assay.

Standard solution: 0.001 mg/mL of USP Hydroxychloroquine Sulfate RS in Solution A from Standard stock solution.

Sample stock solution: Nominally 1.0 mg/mL of hydroxychloroquine sulfate in Solution A prepared as follows. Transfer a portion of finely ground powder, from NLT 20 Tablets, equivalent to about 200 mg of hydroxychloroquine sulfate, to a 200-mL volumetric flask and add Solution A to about 75% of the flask volume. Sonicate for NLT 10 min or until solids are dissolved. Dilute with Solution A to volume.

Sample solution: Nominally 0.1 mg/mL of hydroxychloroquine sulfate in Solution A from Sample stock solution. Pass through a suitable filter.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 2.0-mm × 10-cm; 2-µm packing L1

Column temperature: 35°

Flow rate: 0.8 mL/min

Injection volume: 2 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 5.0%

Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of hydroxychloroquine 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)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

The reporting threshold is 0.1%.

Table 2

^a 2-({4-[(7-Chloroquinolin-4-yl)amino]pentyl}amino)ethan-1-ol.

^b Process impurity monitored in the drug substance monograph.

^c 2-({4-[(7-Chloroquinolin-4-yl)amino]pentyl}ethylamino)ethyl acetate.

^d 2-({4-[(7-Chloroquinolin-4-yl)amino]pentyl}ethylamino)ethyl hydrogen sulfate.

^e 4,7-Dichloroquinoline.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers.

LABELING: The labeling states the Dissolution test used only if Test 1 is not used.

USP REFERENCE STANDARDS (11)

USP Hydroxychloroquine Sulfate RS