Irbesartan
(ir'' be sar' tan).
Click to View Image
C25H28N6O 428.53
1,3-Diazaspiro[4.4]non-1-en-4-one, 2-butyl-3-[[2¢-(1H-tetrazol-5-yl)[1,1¢-biphenyl]-4-yl]methyl]-.
2-Butyl-3-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]-1,3-diazaspiro[4.4]non-1-en-4-one [138402-11-6].
» Irbesartan contains not less than 98.0 percent and not more than 102.0 percent of C25H28N6O, calculated on the anhydrous basis.
Packaging and storage— Preserve in tight containers, and store at a temperature below 30.
USP Reference standards 11
USP Irbesartan RS Click to View Structure
USP Irbesartan Related Compound A RS
1-Pentanoylamino-cyclopentanecarboxylic acid [2¢-(1H-tetrazol-5-yl)-byphenyl-4-ylmethyl]-amide.
    C25H30N6O2     446.54
Identification—
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Water, Method I 921: not more than 0.5%.
Limit of azide—
Mobile phase— Prepare a filtered and degassed 0.1 N sodium hydroxide solution (see System Suitability under Chromatography 621).
Standard solution— Transfer about 25 mg of sodium azide, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix. Pipet 250 µL of this solution into a 200-mL volumetric flask, dilute with Mobile phase to volume, and mix. This solution contains about 0.312 µg of sodium azide per mL.
Test solution— Transfer about 100 mg of Irbesartan, accurately weighed, to a 5-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a conductimetric detector [note—A suitable background suppression unit may be used. ] and a 4.0-mm × 25-cm column that contains packing L31. The flow rate is about 1.0 mL per 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 200 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak areas for azide. Calculate the amount of azide, in ppm, in the portion of Irbesartan taken by the formula:
1000(CS / CT)(42.02/65.01)(rU / rS)
in which CS is the concentration, in µg per mL, of sodium azide in the Standard solution; CT is the concentration, in mg per mL, of Irbesartan in the Test solution; rU is the peak area for azide obtained from the Test solution; and rS is the peak area for azide obtained from the Standard solution: not more than 10 ppm of azide is found.
Related compounds—
pH 3.2 Phosphate buffer and Mobile phase —Proceed as directed in the Assay.
Standard solution— Prepare as directed for the System suitability solution in the Assay.
Test solution— Dissolve an accurately weighed quantity of Irbesartan in methanol to obtain a solution having a known concentration of about 1 mg per mL.
Chromatographic system (see Chromatography 621)— Proceed as directed in the Assay. Chromatograph the Standard solution and 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 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the area for the irbesartan related compound A peak. Calculate the percentage of irbesartan related compound A in the portion of Irbesartan taken by the formula:
100(CS / CT)(rU / rS)
in which CS is the concentration, in mg per mL, of USP Irbesartan Related Compound A RS in the Standard solution; CT is the concentration, in mg per mL, of Irbesartan in the Test solution; rU is the peak response for irbesartan related compound A obtained from the Test solution; and rS is the peak response for irbesartan related compound A obtained from the Standard solution.
Calculate the percentage of other impurities in the portion of Irbesartan taken by the formula:
100(CS / CT)(rU / rS)
in which CS is the concentration, in mg per mL, of USP Irbesartan RS in the Standard solution; CT is the concentration, in mg per mL, of Irbesartan in the Test solution; and rU and rS are the peak responses for each of the other impurities and USP Irbesartan RS obtained from the Test solution and the Standard solution, respectively: not more than 0.2% of irbesartan related compound A is found; not more than 0.1% of any other impurity is found; and not more than 0.5% of total impurities is found.
Assay—
pH 3.2 Phosphate buffer— Mix 5.5 mL of phosphoric acid with about 950 mL of water, and adjust pH to 3.2 with triethylamine.
Mobile phase— Prepare a filtered and degassed mixture of pH 3.2 phosphate buffer and acetonitrile (67:33). Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution— Dissolve accurately weighed quantities of USP Irbesartan RS and USP Irbesartan Related Compound A RS in methanol to obtain a solution having a known concentration of about 0.05 mg per mL of each USP Reference Standard.
Standard preparation— Dissolve an accurately weighed quantity of USP Irbesartan RS in methanol to obtain a solution having a known concentration of about 0.5 mg per mL.
Assay preparation— Transfer about 50 mg of Irbesartan, 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 that contains packing L1. The flow rate is about 1.0 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.8 for irbesartan related compound A and 1.0 for irbesartan; the resolution, R, between irbesartan and irbesartan related compound A is 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 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for all the peaks. Calculate the quantity, in mg, of C25H28N6O in the portion of Irbesartan taken by the formula:
100C(rU / rS)
in which C is the concentration, in mg per mL, of USP Irbesartan RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison
1-301-816-8349
(SM22010) Monographs - Small Molecules 2
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
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