Omeprazole

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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1 DEFINITION

Omeprazole contains NLT 98.0% and NMT 102.0% of omeprazole (C₁₇H₁₉N₃O₃S), calculated on the dried basis.

2 IDENTIFICATION

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

Change to read:

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

3 ASSAY

Procedure

Buffer:

Dissolve 0.725 g of monobasic sodium phosphate and 4.472 g of anhydrous dibasic sodium phosphate in 1000 mL of water. Dilute 250 mL of this solution with water to 1000 mL. If necessary, adjust with phosphoric acid to a pH of 7.6.

Mobile phase:

Acetonitrile and Buffer (1:3)

Diluent:

Acetonitrile and 0.01 M sodium borate (1:3)

Standard solution:

0.2 mg/mL of USP Omeprazole RS in Diluent

System suitability solution:

0.1 mg/mL of USP Omeprazole RS in Diluent from the Standard solution

Sample solution:

0.2 mg/mL of Omeprazole in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.6-mm × 15-cm; 5-µm packing L7

Flow rate: 0.8 mL/min

Injection volume: 20 µL

System suitability

Sample: System suitability solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of omeprazole (C₁₇H₁₉N₃O₃S) in the portion of Omeprazole taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Cₛ = concentration of USP Omeprazole RS in the Standard solution (mg/mL)

Cᵤ = concentration of Omeprazole in the Sample solution (mg/mL)

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Solution A:

Dissolve 0.725 g of monobasic sodium phosphate and 4.472 g of anhydrous dibasic sodium phosphate in 1000 mL of water. Dilute 250 mL of this solution with water to 1000 mL. Adjust with phosphoric acid to a pH of 7.0.

Solution B:

Acetonitrile

Mobile phase:

See Table 1. Return to the original conditions, and re-equilibrate the system for about 10 min.

Table 1

Diluent:

Solution A and Solution B (3:1)

System suitability solution:

0.6 mg/mL of USP Omeprazole RS, 0.6 µg/mL each of USP Omeprazole Related Compound A RS, USP Omeprazole Related Compound E RS, USP Omeprazole Related Compound I RS, and 5-methoxy-1H-benzimidazol-2-thiol in Diluent.

[Note—This solution is stable for 14 h when stored at 4°.]

Standard solution:

6.0 µg/mL of USP Omeprazole RS in Diluent.

[Note—This solution is stable for 14 h when stored at 4°.]

Sample solution:

0.6 mg/mL of Omeprazole in Diluent.

[Note—Inject within 1 h of preparation.]

Sensitivity solution:

0.3 µg/mL of USP Omeprazole RS from the Standard solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 264 nm

Column: 4.6-mm × 25-cm; 5-µm packing L7

Flow rate: 0.8 mL/min

Injection volume: 40 µL

Autosampler temperature: 4°

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements

Resolution: NLT 2.0 between omeprazole and omeprazole related compound A, System suitability solution

Relative standard deviation: NMT 5%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Omeprazole taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × (1/F) × 100

rᵤ = peak response of each impurity from the Sample solution

rₛ = peak response of omeprazole from the Standard solution

Cₛ = concentration of USP Omeprazole RS in the Standard solution (mg/mL)

Cᵤ = concentration of Omeprazole in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. Disregard any peak below 0.05%.

ᵃ 2-[(RS)-[(3,5-Dimethylpyridin-2-yl)methyl]sulfinyl]-5-methoxy-1H-benzimidazole.

ᵇ 2-[(RS)-[4-Chloro-3,5-dimethylpyridin-2-yl)methyl]sulfinyl]-5-methoxy-1H-benzimidazole.

ᶜ 5-Methoxy-2-((4-methoxy-3,5-dimethylpyridin-2-yl)methylthio)-1H-benzimidazole.

ᵈ Omeprazole related compounds F and G (1,3-dimethyl-8-methoxy-12-thioxopyrido[1′,2′:3,4]imidazo[1,2-a]benzimidazol-2(12H)-one and 1,3-dimethyl-9-methoxy-12-thioxopyrido[1′,2′:3,4]imidazo[1,2-a]benzimidazol-2(12H)-one). These impurities are controlled in the test for Limit of Omeprazole Related Compounds F and G.

5 SPECIFIC TESTS

Completeness of Solution 〈641〉

Sample solution: 20 mg/mL of Omeprazole in methylene chloride

Acceptance criteria: Meets the requirements

Limit of Omeprazole Related Compounds F and G

Sample solution: 20 mg/mL of Omeprazole in methylene chloride

Instrumental conditions

Mode: Vis

Analytical wavelength: 440 nm

Cell: 1 cm

Blank: Methylene chloride

Acceptance criteria: The absorbance is NMT 0.10, corresponding to NMT 350 ppm of the sum of omeprazole related compounds F and G.

Loss on Drying 〈731〉

Analysis: Dry a sample under vacuum at 60° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store in a cold place, protected from moisture.

USP Reference Standards 〈11〉

USP Omeprazole RS

USP Omeprazole Related Compound A RS

Omeprazole sulfone;

5-Methoxy-2-[[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfonyl]-1H-benzimidazole.

C₁₇H₁₉N₃O₄S 361.42

USP Omeprazole Related Compound E RS

Omeprazole N-oxide;

4-Methoxy-2-[[(RS)-(5-methoxy-1H-benzimidazol-2-yl)sulfinyl]methyl]-3,5-dimethylpyridine 1-oxide.

C₁₇H₁₉N₃O₄S 361.42

USP Omeprazole Related Compound I RS

Omeprazole sulfone N-oxide;

4-Methoxy-2-[[(5-methoxy-1H-benzimidazol-2-yl)sulfonyl]methyl]-3,5-dimethylpyridine 1-oxide.

C₁₇H₁₉N₃O₅S 377.41