Irbesartan Tablets

» Irbesartan Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of irbesartan (C25H28N6O).

Packaging and storage— Preserve in well-closed containers.

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USP Irbesartan RS

USP Irbesartan Related Compound A RS
1-Pentanoylamino-cyclopentanecarboxylic acid [2¢-(1H-tetrazol-5-yl)-byphenyl-4-ylmethyl]-amide.
C25H30N6O2 446.54

Identification—

A: Infrared Absorption

197K

—

Test specimen: Transfer 1 Tablet into a suitable vial. Add 10 mL of methanol, and sonicate for 10 minutes. Pass the solution through a glass microfiber membrane filter having a 0.45-µm or finer porosity, and evaporate to dryness, using a stream of nitrogen. Mix approximately 1 mg of the residue with approximately 250 mg of potassium bromide, and mix well to obtain a homogenous mixture. The IR absorption spectrum of a potassium bromide dispersion of the residue so obtained exhibits maxima only at the same wavelengths as that of a potassium bromide dispersion of a similar preparation using USP Irbesartan RS.

B: The relative 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.

Dissolution

711

—

Medium: 0.1 N hydrochloric acid; 1000 mL.

Apparatus 2: 50 rpm.

Time: 20 minutes.

Procedure— Determine the amount of C25H28N6O dissolved by employing UV absorption at the wavelength of maximum absorbance at about 244 nm on portions of the solution under test, passed through a 0.45-µm filter of acrylic copolymer on a nylon support,* and suitably diluted with Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Irbesartan RS in the same Medium. Calculate the amount of C25H28N6O dissolved, in percentage, by the formula:

in which AU and AS are the absorbances obtained from the solution under test and the Standard solution, respectively; CS is the concentration, in mg per mL, of the Standard solution; 1000 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and L is the label claim, in mg, of irbesartan.

Tolerances— Not less than 80% (Q) of the labeled amount of C25H28N6O is dissolved in 20 minutes.

Uniformity of dosage units

905

: meet the requirements.

Related compounds—

Buffer solution, Mobile phase, System suitability preparation, and Chromatographic system —Proceed as directed in the Assay.

Standard solution— Use the Standard preparation, prepared as directed in the Assay.

Test solution— Use the Assay preparation.

Procedure— Inject a volume of about 15 µL of the Test solution into the chromatograph, record the chromatogram, and measure the peak responses. Calculate the percentage of each impurity in the portion of Tablets taken by the formula:

100(ri / rs)

in which ri is the peak response for each impurity; and rs is the sum of the responses of all the peaks: not more than 0.2% of irbesartan related compound A is found; not more than 0.2% of any individual impurity is found; and not more than 0.5% of total impurities is found.

Assay—

Buffer solution— Dilute about 5.5 mL of phosphoric acid in approximately 950 mL of water, and add triethylamine, slowly and dropwise, to adjust to a pH of 3.0. Further dilute this solution with water to a final volume of 1 L.

Mobile phase— Prepare a filtered and degassed mixture of Buffer solution and acetonitrile (60:40). Make adjustments if necessary (see System Suitability under Chromatography

621

System suitability preparation— 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 0.1 mg per mL of each of the USP Reference Standards.

Standard preparation— Dissolve an accurately weighed quantity of USP Irbesartan RS in methanol to obtain a solution having a known concentration of about 0.15 mg per mL.

Assay preparation— Weigh and finely powder not fewer than 5 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 15 mg of irbesartan, to a 100-mL volumetric flask. Add methanol up to about three-fourths of the volume of the flask. Sonicate for 15 minutes, with stirring at 5-minute intervals. Dilute with methanol to volume, and pass a portion of this solution through a glass microfiber membrane filter having a 0.45-µm or finer porosity.

Chromatographic system (see Chromatography

621

)— The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 25-cm column that contains packing L1. The flow rate is about 1.0 mL per minute. Chromatograph the System suitability preparation, and record the peak responses as directed for Procedure: the resolution, R, between irbesartan and irbesartan related compound A is not less than 2.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for five replicate injections is not more than 1.5%.

Procedure— Separately inject equal volumes (about 15 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 irbesartan (C25H28N6O) in the portion of Tablets 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.

* A suitable filter is Acrodisc, manufactured by Gelman Sciences and distributed by Pall Corp. (www.pall.com).

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
711	Margareth R.C. Marques, Ph.D. Senior Scientific Liaison 1-301-816-8106	(GCDF2010) General Chapters - Dosage Forms

USP35–NF30 Page 3557

Pharmacopeial Forum: Volume No. 32(3) Page 799