Torsemide Click to View Image C16H20N4O3S 348.42
3-Pyridinesulfonamide,N-[[(1-methylethyl)amino]carbonyl]-4-[(3-methylphenyl)amino]-.
1-Isopropyl-3-[(4-m-toluidino-3-pyridyl)sulfonyl]urea [56211-40-6]. »Torsemide contains not less than 98.0percent and not more than 102.0percent of C16H20N4O3S,calculated on the anhydrous basis. Packaging and storage— Preserve in well-closed containers. USP Reference standards á11ñ USP Torsemide RS.USP Torsemide Related Compound A RS.USP Torsemide Related Compound B RS.USP Torsemide Related Compound C RS. Identification— A: Infrared Absorption á197Kñ. B: The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay. Water,Method Iá921ñ: not more than 0.8%. Residue on ignition á281ñ: not more than 0.1%. Heavy metals,Method IIá231ñ: 0.001%. Related compounds— 0.02M Potassium phosphate buffer and Mobile phase— Prepare as directed in the Assay. Resolution solution— Transfer about 3mg each of USP Torsemide RSand USP Torsemide Related Compound A RSto a 10-mLvolumetric flask,add 3mLof methanol,mix,and sonicate for not less than 8minutes.Add 4.5mLof 0.02M Potassium phosphate buffer,cool to room temperature,dilute with Mobile phaseto volume,and mix. Standard solution— Transfer about 8mg each of USP Torsemide Related Compound A RS,USP Torsemide Related Compound B RS,and USP Torsemide Related Compound C RS,accurately weighed,to a 100-mLvolumetric flask,add 30mLof methanol,mix,and sonicate for not less than 8minutes.Add 45mLof 0.02M Potassium phosphate buffer,cool to room temperature,dilute with Mobile phaseto volume,and mix.Quantitatively dilute a portion of this solution with Mobile phaseto obtain a solution having a known concentration of about 0.0019mg per mL. Test solution— Use the Assay preparation. Chromatographic system— Prepare as directed in the Assay.Chromatograph the Resolution solutionand the Standard solution,and record the peak responses over a period three times the retention time of torsemide as directed for Procedure:the resolution,R,between torsemide and torsemide related compound Ais not less than 1.0;the tailing factors are not more than 2.0;and the relative standard deviation for replicate injections is not more than 10.0%. Procedure— Separately inject equal volumes (about 20µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the peak areas for torsemide related compound A,torsemide related compound B,and torsemide related compound C.Calculate the percentage of each related compound,if present,in the portion of Torsemide taken by the formula: 100(CS/CU)(rU/rS), in which CSis the concentration,in mg per mL,of the relevant USP Reference Standard in the Standard solution;CUis the concentration of Torsemide,in mg per mL,in the Test solution;and rUand rSare the peak areas for the relevant torsemide related compound obtained from the Test solutionand the Standard solution,respectively:not more than 0.2%of torsemide related compound C,not more than 0.3%of torsemide related compound B,and not more than 0.5%of torsemide related compound Aare found.Calculate the percentage of any other impurity in the portion of Torsemide taken by the formula: 100(ri/rs), in which riis the peak response for each other impurity obtained from the Test solution;and rsis the sum of the responses of all the peaks obtained from the Test solution:not more than 0.1%of any other impurity is found,not more than 0.2%of total other impurities is found,and not more than 1.0%of total impurities (including torsemide related compounds A,B,and C)is found. Assay— 0.02M Potassium phosphate buffer— Dissolve 2.7g of monobasic potassium phosphate in about 900mLof water.Adjust with phosphoric acid to a pHof 3.5,dilute with water to 1000mL,and mix. Mobile phase— Prepare a filtered and degassed mixture of 0.02M Potassium phosphate bufferand methanol (3:2).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ). Standard preparation— Transfer about 19mg of USP Torsemide RS,accurately weighed,to a 50-mLvolumetric flask,add 15mLof methanol,mix,and sonicate for not less than 8minutes.Add 22.5mLof 0.02M Potassium phosphate buffer,cool to room temperature,dilute with Mobile phaseto volume,and mix. Assay preparation— Transfer about 38mg of Torsemide,accurately weighed,to a 100-mLvolumetric flask,add 30mLof methanol,mix,and sonicate for not less than 8minutes.Add 45mLof 0.02M Potassium phosphate buffer,cool to room temperature,dilute with Mobile phaseto volume,and mix. Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 288-nm detector and a 4.6-mm ×15-cm column that contains 7-µm packing L1.The flow rate is about 1.5mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the tailing factor is not more than 2.0;and the relative standard deviation for replicate injections is not more than 2.0%. Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the amount,in mg,of C16H20N4O3Sin the portion of Torsemide taken by the formula: 100C(rU/rS), in which Cis the concentration,in mg per mL,of USP Torsemide RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively. Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate Expert Committee:(PA5)Pharmaceutical Analysis 5 USP28–NF23Page 1952 Pharmacopeial Forum:Volume No.28(2)Page 382 Phone Number:1-301-816-8305