Amiloride Hydrochloride
;)
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 98.0percent and not more than 101.0percent of C6H8ClN7O·HCl,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers.
Identification—
A:
Infrared Absorption á197Mñ.
Solution:
600µg per mLof water,diluted quantitatively and stepwise with 0.1Nhydrochloric acid to a concentration of about 9.6µg per mL.
C:
It responds to the tests for Chloride á191ñ.
Acidity—
Dissolve 1.0g in 100mLof a mixture of methanol and water (1:1),and titrate with 0.10Nsodium hydroxide,determining the endpoint potentiometrically:not more than 0.30mLis required (0.1%as HCl).
Loss on drying (see Thermal Analysis á891ñ)—
[NOTE—The 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 10mg of amiloride hydrochloride,accurately weighed.Heat the specimen at the rate of 10
per minute between ambient temperature and 225in an atmosphere of nitrogen at a flow rate of 40mLper minute.From the thermogram determine the accumulated loss in weight between ambient temperature and about 200on the plateau:it loses not less than 11.0%and not more than 13.0%of its weight.
per minute between ambient temperature and 225in an atmosphere of nitrogen at a flow rate of 40mLper minute.From the thermogram determine the accumulated loss in weight between ambient temperature and about 200on the plateau:it loses not less than 11.0%and not more than 13.0%of its weight.
Residue on ignition á281ñ:
not more than 0.1%.
Heavy metals,Method IIá231ñ:
0.002%.
Chromatographic purity—
Standard preparations—
Prepare a series of solutions,A,B,C,D,E,and F,of USP Amiloride Hydrochloride RSin a mixture of methanol and chloroform (4:1)having concentrations of 4000,40,20,8,4,and 2µg per mL,respectively.
Test preparation—
Prepare a solution of Amiloride Hydrochloride in a mixture of methanol and chloroform (4:1)having a concentration of 4mg per mL.
Procedure—
Separately apply 5-µLportions of Standard preparations A,B,C,D,E,and Fand the Test preparationto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)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 3Nammonium 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 UVlight:the RFvalue of the principal spot obtained from the Test preparationcorresponds to that obtained from Standard preparation A.Estimate the levels of any additional spots observed in the chromatogram of the Test preparationby 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%).
Organic volatile impurities,Method Vá467ñ:
meets the requirements.
Solvent—
Use dimethyl sulfoxide.
Assay—
Dissolve about 450mg of Amiloride Hydrochloride,accurately weighed,in 100mLof glacial acetic acid,add 10mLof mercuric acetate TSand 15mLof dioxane,and mix.Add crystal violet TS,and titrate with 0.1Nperchloric acid VSto a blue endpoint.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nperchloric acid is equivalent to 26.61mg of C6H8ClN7O·HCl.
Auxiliary Information—
Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 117
Phone Number:1-301-816-8305