Irbesartan
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]; UNII: J0E2756Z7N.
DEFINITION
Irbesartan contains NLT 98.0% and NMT 102.0% of irbesartan (C25H28N6O), calculated on the anhydrous basis.
IDENTIFICATION
Change to read:
• A. SPECTROSCOPIC IDENTIFICATION TESTS <197>, Infrared Spectroscopy: 197K (CN 1-MAY-2020)
• B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
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 = (ru /rs ) × (Cs /Cu) × 100
ru = peak response of Irbesartan from the Sample solution
rs = peak response of Irbesartan from the Standard solution
Cs = concentration of USP Irbesartan RS in the Standard solution (mg/mL)
Cu = concentration of Irbesartan in the Sample solution (mg/mL)
Acceptance criteria: 98.0%-102.0% on the anhydrous basis
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 = (ru /rs) × (Cs/Cu) × (Mr1 /Mr2) × F
ru = peak area of azide from the Sample solution
rs = peak area of azide from the Standard solution
Cs = concentration of sodium azide in the Standard solution (µg/mL)
Cu = concentration of Irbesartan in the Sample solution (mg/mL)
Mr1 = molecular weight of azide, 42.02
Mr2 = 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 = (ru /rs ) × (Cs /Cu ) × 100
ru = peak response of irbesartan related compound A from the Sample solution
rs = peak response of irbesartan related compound A from the Standard solution
Cs = concentration of USP Irbesartan Related Compound A RS in the Standard solution (mg/mL)
Cu = concentration of Irbesartan in the Sample solution (mg/mL)
Calculate the percentage of any other impurity in the portion of Irbesartan taken:
Result = (ru /rs ) × (Cs /Cu ) × 100
ru = peak response of any other impurity from the Sample solution
rs = peak response of Irbesartan from the Standard solution
Cs = concentration of USP Irbesartan RS in the Standard solution (mg/mL)
Cu = concentration of Irbesartan in the Sample solution (mg/mL)
Acceptance criteria
Irbesartan related compound A: NMT 0.2%
Any other impurity: NMT 0.1%
Total impurities: NMT 0.5%
SPECIFIC TESTS
• WATER DETERMINATION, Method I <921>: NMT 0.5%
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.
C25H30N6O 446.54
Contact: Dr. Alvin Huang
Mobile/Wechat/WhatsApp: +86-15601663162
E-Mail: alvin@ruifuchem.com
Post time: May-31-2024