Chloroquine Phosphate Tablets

General Notices

Action and use

Antiprotozoal (malaria).

Definition

Chloroquine Phosphate Tablets contain Chloroquine Phosphate.

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

Content of chloroquine phosphate, C18H26ClN3,2H3PO4

92.5 to 107.5% of the stated amount.

Identification

A. Dissolve a quantity of the powdered tablets containing 0.1 g of Chloroquine Phosphate 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 chloroquine (RS 054).
B. Extract a quantity of the powdered tablets containing 25 mg of Chloroquine Phosphate with 20 mL of water, filter and add 8 mL of picric acid solution R1 to the filtrate. The melting point of the precipitate, after washing successively with water, ethanol (96%) and ether, is about 207°, Appendix V A.
C. Extract a quantity of the powdered tablets containing 0.5 g of Chloroquine Phosphate with 25 mL of water and filter. To the filtrate add 2.5 mL of 5m sodium hydroxide and extract with three 10 mL quantities of ether. The aqueous layer, after neutralisation with 2m nitric acid, yields the reactions characteristic of phosphates, Appendix VI.

TESTS

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using as the medium 900 mL of 0.1m hydrochloric acid and rotating the basket at 100 revolutions per minute. Withdraw a sample of 10 mL of the medium. Measure the absorbance of a layer of suitable thickness of the filtered sample, suitably diluted if necessary, at the maximum at 344 nm, Appendix II B. Calculate the total content of chloroquine phosphate, C18H26ClN3,2H3PO4, in the medium taking 371 as the value of A(1%, 1 cm) at the maximum at 344 nm.

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using silica gel GF254 as the coating substance and a mixture of 50 volumes of chloroform, 40 volumes of cyclohexane and 10 volumes of diethylamine as the mobile phase. Apply separately to the plate 2 µL of each of the following solutions. For solution (1) shake a quantity of the powdered tablets containing 1 g of Chloroquine Phosphate with 20 mL of water for 30 minutes, centrifuge and use the supernatant liquid; if necessary filter through a glass fibre paper. For solution (2) dilute 1 mL of solution (1) to 100 mL with water. For solution (3) dilute 25 mL of solution (2) to 50 mL with water. After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm). Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) and not more than one such spot is more intense than the spot in the chromatogram obtained with solution (3).

Assay

Weigh and powder 20 tablets. Dissolve a quantity of the powder containing 0.5 g of Chloroquine Phosphate in 20 mL of 1m sodium hydroxide and extract with four 25-mL quantities of chloroform. Combine the chloroform extracts and evaporate to a volume of about 10 mL. Add 40 mL of anhydrous acetic acid and carry out Method I for non-aqueous titration, Appendix VIII A, determining the end point potentiometrically. Each mL of 0.1m perchloric acid VS is equivalent to 25.79 mg of C18H26ClN3,2H3PO4.

250 mg of Chloroquine Phosphate is approximately equivalent to 155 mg of chloroquine.