Hydroxychloroquine Sulfate Tablets
» Hydroxychloroquine Sulfate Tablets contain not less than 93.0 percent and not more than 107.0 percent of the labeled amount of hydroxychloroquine sulfate (C18H26ClN3O·H2SO4).
Packaging and storage— Preserve in tight, light-resistant containers.
USP Reference standards 11
USP Hydroxychloroquine Sulfate RS Click to View Structure
Identification—
A: 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 test B): the clear filtrate so obtained meets the requirements under —Identification—Organic Nitrogenous Bases 181.
B: The clear filtrate obtained from Identification test A meets the requirements of the tests for Sulfate 191.
C: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution 711
Medium: water; 900 mL.
Apparatus 2: 50 rpm.
Time: 60 minutes.
Procedure— Determine the amount of C18H26ClN3O·H2SO4 dissolved from UV absorbances at the wavelength of maximum absorbance at about 343 nm of filtered portions of the solution under test, suitably diluted with Dissolution Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Hydroxychloroquine Sulfate RS in the same medium.
Tolerances— Not less than 70% (Q) of the labeled amount of C18H26ClN3O·H2SO4 is dissolved in 60 minutes.
Uniformity of dosage units 905: meet the requirements.
Assay—
Mobile phase— To 800 mL of water, add 100 mL of methanol, 100 mL of acetonitrile, 2.0 mL of phosphoric acid, and 96 mg of sodium 1-pentanesulfonate, mix, and filter. Make adjustments if necessary (see System Suitability under Chromatography 621).
Solvent mixture— Prepare a mixture of methanol and water (1:1).
Standard preparation— Dissolve an accurately weighed quantity of USP Hydroxychloroquine Sulfate RS in Solvent mixture, dilute quantitatively with Solvent mixture, and mix to obtain Solution A having a known concentration of about 1 mg per mL. Transfer 5.0 mL of this solution to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix to obtain the Standard preparation having a known concentration of about 0.05 mg per mL.
Resolution solution— Prepare a solution of chloroquine phosphate in methanol having a concentration of 1 mg per mL. Transfer 5.0 mL of this solution to a 100-mL volumetric flask, add 5.0 mL of Solution A, dilute with Mobile phase to volume, and mix.
Assay preparation— Weigh and finely powder not less than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 200 mg of hydroxychloroquine sulfate to a 200-mL volumetric flask, add about 150 mL of Solvent mixture, and mix. Sonicate, with intermittent shaking, for about 15 minutes, and cool to room temperature. Dilute with Solvent mixture to volume, mix, and filter. Transfer 5.0 mL of this solution to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains 5- to 10-µm packing L1. The flow rate is about 1.0 mL per minute. Chromatograph about 20 µL of the Resolution solution, and record the peak responses as directed under Procedure: the resolution, R, between chloroquine and hydroxychloroquine is not less than 1.8. Chromatograph replicate injections of the Standard preparation, and record the peak responses as directed under Procedure: the relative standard deviation is not more than 1.5%.
Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of hydroxychloroquine sulfate (C18H26ClN3O·H2SO4) in the portion of Tablets taken by the formula:
4000C(rU / rS)
in which C is the concentration, in mg per mL, of USP Hydroxychloroquine Sulfate RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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Monograph Behnam Davani, Ph.D., M.B.A.
Senior Scientific Liaison
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(SM12010) Monographs - Small Molecules 1
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(GCDF2010) General Chapters - Dosage Forms
USP35–NF30 Page 3455
Pharmacopeial Forum: Volume No. 34(4) Page 940