Olmesartan Medoxomil

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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C₂₉H₃₀N₆O₆ 558.59

1H-Imidazole-5-carboxylic acid, 4-(1-hydroxy-1-methyl ethyl)-2-propyl-1-[[2′-(1H-tetrazol-5-yl) [1,1′-biphenyl]-4-yl]methyl]-, (5-methyl-2-oxo-1,3- dioxol-4-yl)methyl ester; (5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 1-{[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-4-(2-hydroxypropan-2-yl)-2-propyl-1H imidazole-5-carboxylate CAS RN®: 144689-63-4; UNII: 6M97XTV3HD. 

1 DEFINITION 

Olmesartan Medoxomil contains NLT 98.5% and NMT 101.5% of C₂₉H₃₀N₆O₆, calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION 

Change to read: 

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

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

3 ASSAY 

Procedure 

[Note—The Standard solution and Sample solution are stable for 24 h at 5°.] 

Diluted phosphoric acid: 0.2% phosphoric acid 

Buffer: 0.015 M monobasic potassium phosphate. Adjust the solution with Diluted phosphoric acid (w/v) to a pH of 3.4. Mobile phase: Acetonitrile and Buffer (17:33) 

Diluent 1: Acetonitrile and water (4:1) 

Diluent 2: Acetonitrile and water (2:3) 

Internal standard solution: 0.5 mg/mL of 4-hydroxybenzoic acid isobutyl ester in Diluent 2. [Note—This solution is stable for 1 month at room temperature.] 

Standard stock solution: 1 mg/mL of USP Olmesartan Medoxomil RS in Diluent 1 

Standard solution: 0.05 mg/mL of USP Olmesartan Medoxomil RS from the Standard stock solution and 0.025 mg/mL of p-hydroxybenzoic acid isobutyl ester from the Internal standard solution in Diluent 2 

Sample stock solution: 1 mg/mL of Olmesartan Medoxomil in Diluent 1 

Sample solution: 0.05 mg/mL of Olmesartan Medoxomil from the Sample stock solution and 0.025 mg/mL of p-hydroxybenzoic acid isobutyl ester from the Internal standard solution in Diluent 2 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 250 nm 

Column: 4.6-mm × 15-cm; 5-µm packing L1 

Column temperature: 40° 

Flow rate: 1 mL/min 

Injection size: 10 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Resolution: NLT 4 between olmesartan medoxomil and p-hydroxybenzoic acid isobutyl ester 

Relative standard deviation: NMT 0.5% for the peak ratio of olmesartan medoxomil and the internal standard Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of olmesartan medoxomil in the portion taken: 

Result = (R_U/R_S) × (C_S/C_U) × 100 

R_U = ratio of the peak areas of olmesartan medoxomil and p-hydroxybenzoic acid isobutyl ester from the Sample solution 

R_S = ratio of the peak areas of olmesartan medoxomil and p-hydroxybenzoic acid isobutyl ester from the Standard solution 

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

C_U = concentration of Olmesartan Medoxomil in the Sample solution (mg/mL)  

Acceptance criteria: 98.5%–101.5% on the anhydrous and solvent-free basis 

4 IMPURITIES

Inorganic Impurities 

Residue on Ignition 〈281〉: NMT 0.1%. [Note—The ignition temperature range is 450° to 550°.] 

Organic Impurities 

Procedure 

Buffer: Prepare as directed in the Assay. 

Solution A: Acetonitrile and Buffer (1:4) 

Solution B: Acetonitrile and Buffer (4:1) 

Mobile phase: See the gradient table below. 

System suitability solution: 0.01 mg/mL each of USP Olmesartan Medoxomil RS and USP Olmesartan Medoxomil Related Compound A RS in acetonitrile 

Standard solution: 0.01 mg/mL of USP Olmesartan Medoxomil RS in acetonitrile 

Sample solution: 1 mg/mL of Olmesartan Medoxomil in acetonitrile 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

[Note—A guard column of 4.6-mm × 5-cm of packing L7 may be used.] 

Mode: LC 

Detector: UV 250 nm 

Column: 4.6-mm × 10-cm; 3.5-µm packing L7 

Column temperature: 40° 

Flow rate: 1 mL/min 

Injection size: 10 µL 

System suitability 

Suitability requirements 

Sample: System suitability solution 

Resolution: NLT 5 between olmesartan medoxomil and olmesartan medoxomil related compound A 

Relative standard deviation: NMT 2.0% for the olmesartan medoxomil peak 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each impurity in the portion of Olmesartan Medoxomil taken: 

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100 

r_U = peak response of each impurity from the Sample solution 

r_S = peak response of olmesartan medoxomil from the Standard solution 

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

C_U = concentration of Olmesartan Medoxomil in the Sample solution (mg/mL) 

F = relative response factor (see the Impurity Table) 

Acceptance criteria 

Individual impurities: See the Impurity Table. 

Total impurities: NMT 1.3%. [Note—Disregard any peak below 0.05%.] 

Impurity Table

a 1-{[2′-(1H-Tetrazol-5-yl)biphenyl-4-yl]methyl}-4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylic acid. 

b 1-{[2′-(1H-Tetrazol-5-yl)biphenyl-4-yl]methyl}-4,4-dimethyl-2-propyl-1H-furo[3,4-d]imidazol-6(4H)-one. 

c(5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 1-((2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-4-(prop-1-en-2-yl)-2-propyl-1H-imidazole-5- carboxylate. 

d(5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-(2-hydroxypropan-2-yl)-2-propyl-1-((2′-(2-trityl-2H-tetrazol-5-yl)biphenyl-4-yl)methyl)-1H imidazole-5-carboxylate. 

5 SPECIFIC TESTS 

Limit of Acetone (if present) 

Internal standard solution: 1% solution of 1-butanol in Dimethyl sulfoxide. [Note—This solution is stable for 1 month at room temperature.] Standard solution: 0.37 µL/mL of acetone and 2 µL/mL of 1-butanol from the Internal standard solution in dimethylsulfoxide. [Note—This solution is stable for 8 h at room temperature.] 

Sample solution: 25 mg/mL of Olmesartan Medoxomil and 2 µL/mL of 1-butanol from the Internal standard solution in dimethylsulfoxide. [Note—This solution is stable for 8 h at room temperature.] 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: GC 

Detector: Flame ionization 

Column: 30-m × 0.53-mm column bonded with a 1-µm lm of phase G14 

Column temperature: See the temperature program table below. 

Injection port temperature: 200° 

Detector temperature: 200° 

Autosampler temperature: 80° 

Carrier gas: Helium 

Flow rate: 4 mL/min. [Note—Adjust the ow rate so that the retention time of acetone is 2.5 min.] 

Injection size: 1 mL 

Split ratio: 5:1 

System suitability 

Sample: Standard solution. [Note—Allow the samples to stand for 30 min in the autosampler at 80°.] 

Suitability requirements 

Resolution: NLT 60 between the acetone and 1-butanol peaks 

Relative standard deviation: NMT 5.0% for the peak area ratio of acetone and 1-butanol 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of acetone in the portion of Olmesartan Medoxomil taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of acetone from the Sample solution 

r_S = peak response of acetone from the Standard solution

C_S = concentration of acetone in the Standard solution (mg/mL) 

C_U = concentration of Olmesartan Medoxomil in the Sample solution (mg/mL) 

Acceptance criteria: NMT 0.6% 

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

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in well-closed containers, protect from moisture, and store below 25°. 

USP Reference Standards 〈11〉 

USP Olmesartan Medoxomil RS 

USP Olmesartan Medoxomil Related Compound A RS 

1-{[2′-(1H-Tetrazol-5-yl)biphenyl-4-yl]methyl}-4,4-dimethyl-2-propyl-1H-furo[3,4-d]imidazol-6(4H)-one. 

C₂₄H₂₄N₆O₂ 428.49