Add the following:

Change to read:

Change to read:

A:USP28 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.USP28

Add the following:

Add the following:

Mobile phase— Prepare a filtered and degassed 0.1Nsodium hydroxide solution (see System Suitability under Chromatography á621ñ).

Standard solution— Transfer about 25mg of sodium azide,accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with Mobile phaseto volume,and mix.Pipet 250µLof this solution into a 200-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.This solution contains about 0.312µg of sodium azide per mL.

Test solution— Transfer about 100mg of Irbesartan,accurately weighed,to a 5-mLvolumetric flask,dissolve in and dilute with Mobile phaseto volume,and mix.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a conductimetric detector,and a 4.0-mm ×25-cm column that contains packing L46.The flow rate is about 1.0mLper minute.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the signal to noise ratio for the azide peak is not less than 10.

Procedure— Separately inject equal volumes (about 200µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the peak area for azide peak.Calculate the amount of azide in ppm in the portion of Irbesartan taken by the formula: in which CSis the concentration,in µg per mL,of sodium azide in the Standard solution;CTis the concentration,in mg per mL,of Irbesartan in the Test solution;rUis the peak area for azide obtained from the Test solution;and rSis the peak area for azide obtained from the Standard solution:not more than 10ppm of azide is found.USP28

Delete the following:

Diluent,Triethylamine solution,Mobile phase,and Chromatographic system— Proceed as directed in the Assay.

Test solution— Use the Assay preparation.

Procedure— Inject a volume (about 20µL)of the Test solutioninto the chromatograph,record the chromatogram,and measure the peak responses.Calculate the percentage of each impurity in the portion of Irbesartan taken by the formula: in which riis the peak response for each impurity,and rsis the sum of the responses of all the peaks:not more than 0.5%of any individual impurity is found;and not more than 1.0%of total impurities is found.USP28

Add the following:

pH3.2Phosphate buffer,Mobile phase,and Dilute standard solution— Proceed as directed in the Assay.

Standard solution— Prepare as directed for the System suitability solutionin the Assay.

Chromatographic system(see Chromatography á621ñ)— Proceed as directed in the Assay.Chromatograph the Standard solutionand record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 10µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the area for irbesartan related compound Apeak.Calculate the percentage of irbesartan related compound Ain the portion of Irbesartan taken by the formula: in which CSis the concentration,in mg per mL,of USP Irbesartan Related Compound A RSin the Standard solution;CTis the concentration,in mg per mL,of Irbesartan in the Test solution;rUis the peak response for irbesartan related compound Aobtained from the Test solution;and rSis the peak response for irbesartan related compound Aobtained from the Standard solution:not more than 0.2%of irbesartan related compound Ais found,not more than 0.1%of any other impurity is found;and not more than 0.5%of total impurities is found.USP28

Delete the following:

Change to read:

pH3.2Phosphate buffer— Mix 5.5mLof phosphoric acid with about 950mLof water,and adjust pHto 3.2with triethylamine.

Mobile phase— Prepare a filtered and degassed mixture of pH3.2phosphate buffer and acetonitrile (67:33).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

System suitability solution— Dissolve accurately weighed quantities of USP Irbesartan RSand USP Irbesartan Related Compound A RSin methanol to obtain a solution having a known concentration of about 0.05mg per mLof each USP Reference Standard.

Dilute standard solution— Dissolve an accurately weighed quantity of USP Irbesartan RSin methanol to obtain a solution having a known concentration of about 1µg per mL.

Standard preparation— Dissolve an accurately weighed quantity of USP Irbesartan RSin methanol to obtain a solution having a known concentration of about 0.5mg per mL.

Assay preparation— Transfer about 50mg of Irbesartan,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 that contains packing L1.The flow rate is about 1.0mLper minute.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.8for irbesartan related compound Aand 1.0for irbesartan;the resolution,R,between irbesartan and irbesartan related compound Ais not less than 2.0.Chromatograph the Standard preparation,and record the peak response as directed for Procedure:the standard deviation for replicate injections is not more than 1.0%.

Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for all the peaks.Calculate the quantity,in mg,of C25H28N6Oin the portion of Irbesartan taken by the formula: in which Cis the concentration,in mg per mL,of USP Irbesartan RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.USP28