A:Infrared Absorption á197Mñ—

B:Ultraviolet Absorption á197Uñ—

C: It meets the requirements of the test for Potassium á191ñ.

Standard solution— Accurately prepare a solution having a known concentration of about 0.05mg per mLof cyclohexane and 0.05mg per mLof isopropyl alcohol in dimethylformamide.

Test solution— Transfer 500mg of Losartan Potassium to a 10-mLvolumetric flask that contains 5mLof dimethylformamide,dissolve using a vortex mixer,dilute with dimethylformamide to volume,and mix.

Chromatographic system (see Chromatography á621ñ)— The gas chromatograph is equipped with a flame-ionization detector and contains a 0.53-mm ×30-m column containing packing G27of 1.5-µm film thickness.The carrier gas is helium,flowing at a rate of about 6mLper minute.The chromatograph is programmed as follows.Initially the column is maintained at 50for 5minutes,then the temperature is increased at a rate of 30per minute to 200and maintained at 200for 5minutes.The injection port and detector block temperatures are each maintained at 220.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the retention times are about 2minutes for isopropyl alcohol and 4minutes for cyclohexane;the resolution,R,between cyclohexane and isopropyl alcohol is not less than 4.0;and the relative standard deviation for replicate injections is not more than 8.0%.

Procedure— Inject equal volumes (about 1µL)of the Test solution and the Standard solution into the gas chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the percentages of cyclohexane and isopropyl alcohol taken by the formula: in which Cis the concentration,in mg per mL,of cyclohexane or isopropyl alcohol in the Standard solution;Iis the concentration,in mg per mL,of Losartan in the Test solution;and rUand rSare the responses of cyclohexane or isopropyl alcohol in the Test solutionand the Standard solution,respectively:not more than 0.1%of cyclohexane and not more than 0.2%of isopropyl alcohol is found.

Solution A— Prepare a 0.1%solution of phosphoric acid in water.

Solution B— Use acetonitrile.

Mobile phase— Use variable mixtures of Solution Aand Solution Bas directed for Chromatographic system.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ.

System suitability solution— Dissolve an accurately weighed quantity of USP Losartan Potassium RSand triphenylmethanol in methanol,and dilute quantitatively,and stepwise if necessary,to obtain a solution having known concentrations of about 0.3mg per mLand 0.002mg per mL,respectively.

Test solution— Transfer about 30mg of Losartan Potassium,accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with methanol to volume,and mix.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 220-nm detector and a 4.0-mm ×25-cm column containing packing L1.The flow rate is about l mLper minute.The chromatograph is programmed as follows. Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the relative retention times are about 1.0for losartan and 1.9for triphenylmethanol;and the tailing factor for losartan is not more than 1.6.[NOTE—The typical retention time for triphenylmethanol is about 20minutes.]

Procedure— Inject a volume (about 10µL)of the Test solutioninto the chromatograph,record the chromatogram,and measure all the peak responses.Calculate the percentage of each impurity in the portion of Losartan Potassium taken by the formula: in whichriis the peak response for each impurity;and rsis the sum of the responses for all the peaks:not more than 0.2%of any individual impurity is found;and not more than 0.5%of total impurities is found.

Solution AandSolution B— Proceed as directed in the test for Chromatographic purity.

Mobile phase— Prepare a filtered and degassed mixture of Solution Aand Solution B(3:2).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Standard preparation— Dissolve an accurately weighed quantity of USP Losartan Potassium RSin methanol,and dilute quantitatively,and stepwise if necessary,to obtain a solution having a known concentration of about 0.25mg per mL.

Assay preparation— Transfer about 25mg of Losartan Potassium,accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with methanol to volume,and mix.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 254-nm detector and a 4.0-mm ×25-cm column that contains packing L1.The flow rate is about 1.0mLper minute.The column temperature is maintained at about 35.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency is not less than 5600theoretical plates;the tailing factor is not more than 1.4;and the relative standard deviation for replicate injections is not more than 0.5%.

Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C22H22ClKN6Oin the portion of Losartan Potassium taken by the formula: in which Cis the concentration,in mg per mL,of USP Losartan Potassium RSin the Standard preparation;andrUand rSare the peak areas for the losartan peak obtained from the Assay preparationand the Standard preparation,respectively.USP28