Irbesartan

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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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 CAS RN®: 138402-11-6; UNII: J0E2756Z7N. 

1 DEFINITION 

Irbesartan contains NLT 98.0% and NMT 102.0% of irbesartan (C₂₅H₂₈N₆O), calculated on the anhydrous basis.

2 IDENTIFICATION 

Change to read: 

Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. 

3 ASSAY 

Procedure 

Buffer: Phosphoric acid and water (v/v) (5.5:950). Adjust with triethylamine to a pH of 3.2. 

Mobile phase: Acetonitrile and Buffer (330:670) 

System suitability solution: 0.05 mg/mL each of USP Irbesartan RS and USP Irbesartan Related Compound A RS in methanol Standard solution: 0.5 mg/mL of USP Irbesartan RS in methanol 

Sample solution: 0.5 mg/mL of Irbesartan in methanol 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 220 nm 

Column: 4.0-mm × 25-cm; packing L1 

Flow rate: 1 mL/min 

Injection volume: 10 µL 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—The relative retention times for irbesartan related compound A and irbesartan are 0.8 and 1.0, respectively.] Suitability requirements 

Resolution: NLT 2.0 between irbesartan and irbesartan related compound A, System suitability solution Relative standard deviation: NMT 1.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of irbesartan (C₂₅H₂₈N₆O) in the portion of Irbesartan taken: 

Result = (r_U/r_S) × (C_S/C_U) x 100 

r_U = peak response of irbesartan from the Sample solution

r_S = peak response of irbesartan from the Standard solution 

C_S = concentration of USP Irbesartan RS in the Standard solution (mg/mL)

C_U = concentration of irbesartan in the Sample solution (µg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis 

4 IMPURITIES 

Limit of Azide 

Mobile phase: 0.1 N sodium hydroxide solution 

Standard stock solution: 0.25 mg/mL of sodium azide in Mobile phase 

Standard solution: 0.312 µg/mL of sodium azide in Mobile phase, from the Standard stock solution 

Sample solution: 20 mg/mL of Irbesartan in Mobile phase 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: Conductimetric with a suitable background suppressor unit 

Column: 4.0-mm × 25-cm; L31 packing 

Flow rate: 1 mL/min 

Injection volume: 200 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Signal-to-noise ratio: NLT 10 for the azide peak 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the amount of azide, in ppm, in the portion of Irbesartan taken: 

Result = (r_U/r_S) × (C_S/C_U ) × (M_r1/M_r2) × F 

r_U = peak area of azide from the Sample solution

r_S = peak area of azide from the Standard solution 

C_S = concentration of USP sodium azide RS in the Standard solution (µg/mL) 

C_U = concentration of irbesartan in the Sample solution (µg/mL)

M_r1 = molecular weight of azide, 42.02 

M_r2 = molecular weight of sodium azide, 65.01 

F = unit conversion factor, 1000 

Acceptance criteria: NMT 10 ppm 

Organic Impurities 

Buffer and Mobile phase: Prepare as directed in the Assay. 

Standard solution: Use the System suitability solution, prepared as directed in the Assay. 

Sample solution: 1 mg/mL of Irbesartan in methanol 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 220 nm 

Column: 4.0-mm × 25-cm; packing L1 

Flow rate: 1 mL/min 

Injection volume: 10 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of irbesartan related compound A in the portion of Irbesartan taken: 

Result = (r_U/r_S) × (C_S/C_U) x 100 

r_U = peak response of irbesartan related compound A from the Sample solution

r_S = peak response of irbesartan related compound A from the Standard solution 

C_S = concentration of USP Irbesartan Related Compound A RS in the Standard solution (mg/mL)

C_U = concentration of irbesartan in the Sample solution (µg/mL)

Calculate the percentage of any other impurity in the portion of Irbesartan taken:

Result = (r_U/r_S) × (C_S/C_U) x 100 

r_U = peak response of any other impurity from the Sample solution

r_S = peak response of irbesartan from the Standard solution 

C_S = concentration of USP irbesartan RS in the Standard solution (µg/mL) 

C_U = concentration of irbesartan in the Sample solution (µg/mL)

Acceptance criteria 

Irbesartan related compound A: NMT 0.2% 

Any other impurity: NMT 0.1% 

Total impurities: NMT 0.5% 

5 SPECIFIC TESTS 

Water Determination, Method I〈921〉: NMT 0.5% 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight containers, and store at a temperature below 30°. 

USP Reference Standards 〈11〉 

USP Irbesartan RS 

USP Irbesartan Related Compound A RS 

1-Pentanoylamino-cyclopentanecarboxylic acid [2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-amide. 

C₂₅H₃₀N₆O₂ 446.54