Hydroxychloroquine Tablets

General Notices

Action and use

Used in the treatment of rheumatoid arthritis.

Definition

Hydroxychloroquine Tablets contain Hydroxychloroquine Sulfate. They are coated.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of hydroxychloroquine sulfate, C18H26ClN3O,H2SO4

92.5 to 107.5% of the stated amount.

Identification

A. Dissolve a quantity of the powdered tablets containing 0.1 g of Hydroxychloroquine Sulfate in a mixture of 10 mL of water and 2 mL of 2m sodium hydroxide and extract with two 20 mL quantities of chloroform. Wash the chloroform extracts with water, dry with anhydrous sodium sulfate, evaporate to dryness and dissolve the residue in 2 mL of chloroform IR. The infrared absorption spectrum of the resulting solution, Appendix II A, is concordant with the reference spectrum of hydroxychloroquine (RS 182).
B. Shake a quantity of the powdered tablets containing 0.1 g of Hydroxychloroquine Sulfate with 10 mL of water and filter. To the filtrate add 1 mL of 2m hydrochloric acid and 1 mL of barium chloride solution. A white precipitate is produced.

TEST

Disintegration

Maximum time, 45 minutes, Appendix XII A1.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions of the substance being examined in mobile phase A.

(1) Shake a quantity of the powdered tablets containing 200 mg of Hydroxychloroquine Sulfate in 150 mL of mobile phase A, dilute to 200 mL with mobile phase A and filter. Dilute 1 volume of the resulting solution with 10 volumes of mobile phase A.
(2) Dilute 1 volume of solution (1) to 200 volumes.
(3) Dilute 1 volume of solution (2) to 10 volumes.
(4) 0.00005% w/v of 2-[4-[(7-chloro-4-quinolinyl)amino]pentyl] amino ethanol BPCRS.
(5) 0.0001% w/v of hydroxychloroquine sulfate BPCRS and 0.0001% w/v of 2-[4-[(7-chloro-4-quinolinyl)amino]pentyl] amino ethanol BPCRS.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5µm) (Inertsil ODS3 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use a column temperature of 35°.
(e) Use a detection wavelength of 220 nm.
(f) Inject 20 µL of each solution.
mobile phase

Mobile phase A0.2 volumes of orthophosphoric acid, 10 volumes of acetonitrile and 90 volumes of water.

Mobile phase B0.1 volumes of orthophosphoric acid, 20 volumes of water and 80 volumes of acetonitrile.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (5), the resolution between 2-[4-[(7-chloro-4-quinolinyl)amino]pentyl] amino ethanol and hydroxychloroquine is at least 1.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to 2-[4-[(7-chloro-4-quinolinyl)amino]pentyl]aminoethanol is not greater than the area of the principal peak in the chromatogram obtained with solution (4) (0.5%);

the area of any other secondary peak is not greater than the principal peak in the chromatogram obtained with solution (2) (0.5%).

the sum of the areas of any other secondary peaks is not greater than twice the principal peak in the chromatogram obtained with solution (2) (1.0%).

Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (3) (0.05%).

Assay

Carry out the method for liquid chromatography, Appendix III D, using the following solutions of the substance being examined in mobile phase A.

(1) Weigh and powder 20 tablets. Shake a quantity of the powdered tablets containing 0.20 g of Hydroxychloroquine Sulfate with 150 mL of mobile phase A, dilute to 200 mL and filter. Dilute 1 volume of the filtrate to 10 volumes with mobile phase A.
(2) 0.01% w/v hydroxychloroquine sulfate BPCRS.
(3) 0.0001% w/v of hydroxychloroquine sulfate BPCRS and 0.0001% w/v of 2-[4-[(7-chloro-4-quinolinyl)amino]pentyl] amino ethanol BPCRS.
chromatographic conditions

The chromatographic procedure may be carried out using the conditions described under the Related substances test.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between 2-[4-[(7-chloro-4-quinolinyl)amino]pentyl] amino ethanol and hydroxychloroquine is at least 1.0.

determination of content

Calculate the total content of hydroxychloroquine sulfate, C18H26ClN3O,H2SO4, in the tablets using the declared content of C18H26ClN3O,H2SO4 in hydroxychloroquine sulfate BPCRS.