Triamterene Click to View Image C12H11N7 253.26
2,4,7-Triamino-6-phenylpteridine [396-01-0]. »Triamterene contains not less than 98.0percent and not more than 102.0percent of C12H11N7,calculated on the dried basis. Packaging and storage— Preserve in tight,light-resistant containers. USP Reference standards á11ñ USP Triamterene RS. Identification— A: Infrared Absorption á197Mñ. B: Asolution in formic acid solution (1in 1000)shows an intense,bluish fluorescence. Loss on drying á731ñ Dry it in vacuum at 105for 2hours:it loses not more than 1.0%of its weight. Limit of 2,4,6-triamino-5-nitrosopyrimidine— Mobile phase— Prepare a filtered and degassed mixture of 0.01Mpotassium dihydrogen phosphate (adjusted to a pHof 3.0)and methanol (80:20).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ). Standard solution— [NOTE—Heating to 50and sonication may be used to dissolve the 2,4,6-triamino-5-nitrosopyrimidine.]Dissolve an accurately weighed quantity of 2,4,6-triamino-5-nitrosopyrimidine in methanol,and dilute quantitatively if necessary with methanol to obtain a solution having a known concentration of about 10µg per mL. Test solution— Transfer about 1g of Triamterene,accurately weighed,to a 250-mLconical flask.Add 100.0mLof methanol,and stir for 30minutes with heating to 50,cool,and filter. Chromatographic system— The liquid chromatograph is equipped with a 330-nm detector and a 3.9-mm ×30-cm column that contains 10-µm packing L10.The flow rate is about 1.5mLper minute.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.4for 2,4,6-triamino-5-nitrosopyrimidine and 1.0for triamterene;the tailing factor is not more than 1.5;and the relative standard deviation for replicate injections is not more than 2.0%. Procedure— Separately inject equal volumes (about 20µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the percentage of 2,4,6-triamino-5-nitrosopyrimidine in the portion of Triamterene taken by the formula: 10C/W(rU/rS), in which the Cis the concentration,in µg per mL,of 2,4,6-triamino-5-nitrosopyrimidine in the Standard solution;Wis the weight,in mg of triamterene taken;and rUand rSare the peak responses for 2,4,6-triamino-5-nitrosopyrimidine obtained from the Test solutionand the Standard solution,respectively:not more than 0.1%of 2,4,6-triamino-5-nitrosopyrimidine is found. Organic volatile impurities,Method IVá467ñ: meets the requirements. Ordinary impurities á466ñ Test solution— Prepare a solution of Triamterene in dimethyl sulfoxide having a concentration of about 10mg per mL.Quantitatively dilute with methanol to obtain a solution having a concentration of 0.25mg per mL. Standard solutions— Dissolve an accurately weighed quantity of USP Triamterene RSin dimethyl sulfoxide to obtain a solution having a known concentration of about 10mg per mL.Dilute this solution with methanol to obtain solutions having known concentrations of about 0.00025,0.00125,0.0025,and 0.005mg per mL. Procedure— Separately apply 50µLof each of the Standard solutionsand the Test solutionto a 0.5-mm thin-layer chromatographic plate that has been preconditioned by heating at 105for 15minutes and allowed to cool at room temperature in a closed chamber. Eluant: a mixture of ethyl acetate,15Mstronger ammonia water,and methanol (90:10:10). Visualization: 1. Assay— Transfer about 0.5g of Triamterene,accurately weighed,to a 400-mLbeaker,and dissolve in 250mLof a solvent previously prepared by mixing,in the order named and with cooling prior to use,1volume of formic acid,1volume of acetic anhydride,and 2volumes of glacial acetic acid.Titrate with 0.1Nperchloric acid VS,determining the endpoint potentiometrically.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nperchloric acid is equivalent to 25.33mg of C12H11N7. Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate Expert Committee:(PA5)Pharmaceutical Analysis 5 USP28–NF23Page 1965 Pharmacopeial Forum:Volume No.27(1)Page 1823 Phone Number:1-301-816-8305