(a mil' oh ride hye'' droe klor' ide).
Pyrazinecarboxamide, 3,5-diamino-N-(aminoiminomethyl)-6-chloro-, monohydrochloride dihydrate.
N-Amidino-3,5-diamino-6-chloropyrazinecarboxamide monohydrochloride dihydrate [17440-83-4].
» Amiloride Hydrochloride contains not less than 98.0 percent and not more than 101.0 percent of C6H8ClN7O·HCl, calculated on the dried basis.
Packaging and storage Preserve in well-closed containers.
USP Reference standards 11
Solution: 600 µg per mL of water, diluted quantitatively and stepwise with 0.1 N hydrochloric acid to a concentration of about 9.6 µg per mL.
C: It responds to the tests for Chloride 191.
Acidity Dissolve 1.0 g in 100 mL of a mixture of methanol and water (1:1), and titrate with 0.10 N sodium hydroxide, determining the endpoint potentiometrically: not more than 0.30 mL is required (0.1% as HCl).
Loss on drying (see Thermal Analysis 891) [noteThe quantity taken for the determination may be adjusted, if necessary, for instrument sensitivity. ] Determine the percentage of volatile substances by thermogravimetric analysis on an appropriately calibrated instrument, using about 10 mg of amiloride hydrochloride, accurately weighed. Heat the specimen at the rate of 10 per minute between ambient temperature and 225 in an atmosphere of nitrogen at a flow rate of 40 mL per minute. From the thermogram determine the accumulated loss in weight between ambient temperature and about 200 on the plateau: it loses not less than 11.0% and not more than 13.0% of its weight.
Residue on ignition 281: not more than 0.1%.
Heavy metals, Method II 231: 0.002%.
Standard preparations Prepare a series of solutions, A, B, C, D, E, and F, of USP Amiloride Hydrochloride RS in a mixture of methanol and chloroform (4:1) having concentrations of 4000, 40, 20, 8, 4, and 2 µg per mL, respectively.
Test preparation Prepare a solution of Amiloride Hydrochloride in a mixture of methanol and chloroform (4:1) having a concentration of 4 mg per mL.
Procedure Separately apply 5-µL portions of Standard preparations A, B, C, D, E, and F and the Test preparation to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel and previously washed with methanol. Dry the spots with a stream of nitrogen, and develop the chromatograms in a solvent system consisting of a mixture of tetrahydrofuran and 3 N ammonium hydroxide (15:2) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, allow to air-dry, and examine the plate under long-wavelength UV light: the RF value of the principal spot obtained from the Test preparation corresponds to that obtained from Standard preparation A. Estimate the levels of any additional spots observed in the chromatogram of the Test preparation by comparison with the principal spots in the chromatograms of Standard preparations B, C, D, E, and F: the sum of the intensities of any additional spots observed is not greater than that of the principal spot obtained from Standard preparation B (equivalent to 1%).
Assay Dissolve about 450 mg of Amiloride Hydrochloride, accurately weighed, in 100 mL of glacial acetic acid, add 10 mL of mercuric acetate TS and 15 mL of dioxane, and mix. Add crystal violet TS, and titrate with 0.1 N perchloric acid VS to a blue endpoint. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 26.61 mg of C6H8ClN7O·HCl.
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USP35NF30 Page 2161