A: Infrared Absorption 197M—

B: Ultraviolet Absorption 197U—

C: It meets the requirements of the test for Potassium 191.

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

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

Chromatographic system (see Chromatography 621)— The gas chromatograph is equipped with a flame-ionization detector and contains a 0.53-mm × 30-m column containing packing G27 of 1.5-µm film thickness. The carrier gas is helium, flowing at a rate of about 6 mL per minute. The chromatograph is programmed as follows. Initially the column is maintained at 50 for 5 minutes, then the temperature is increased at a rate of 30 per minute to 200 and maintained at 200 for 5 minutes. 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 2 minutes for isopropyl alcohol and 4 minutes 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 1 µL) 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 C is the concentration, in mg per mL, of cyclohexane or isopropyl alcohol in the Standard solution; I is the concentration, in mg per mL, of Losartan in the Test solution; and rU and rS are the responses of cyclohexane or isopropyl alcohol in the Test solution and 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 A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621.

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

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

Chromatographic system (see Chromatography 621)— 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 mL per 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 1.0 for losartan and 1.9 for triphenylmethanol; and the tailing factor for losartan is not more than 1.6. [NOTE—The typical retention time for triphenylmethanol is about 20 minutes.]

Procedure— Inject a volume (about 10 µL) of the Test solution into 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 which ri is the peak response for each impurity; and rs is 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.

(Official January 1, 2007)

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

Mobile phase— Prepare a filtered and degassed mixture of Solution A and Solution B (3:2). Make adjustments if necessary (see System Suitability under Chromatography 621).

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

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

Chromatographic system (see Chromatography 621)— 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 1.0 mL per 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 5600 theoretical 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 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C22H22ClKN6O in the portion of Losartan Potassium taken by the formula: in which C is the concentration, in mg per mL, of USP Losartan Potassium RS in the Standard preparation; and rU and rS are the peak areas for the losartan peak obtained from the Assay preparation and the Standard preparation, respectively.