Omeprazole Magnesium

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 Magnesium contains NLT 97.5% and NMT 102.0% of omeprazole magnesium (C₁₇H₁₉MgN₃O₃S₂), calculated on the anhydrous basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

 B. The Sample solution, prepared and tested as directed in the test for Content of Magnesium, exhibits a significant absorption at the magnesium emission line at 285.2 nm.

Add the following:

▲C. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.▲ (USP 1-May-2021)

3 ASSAY

Change to read:

Procedure

Solution A:

0.181 g/L of sodium phosphate monobasic and 1.118 g/L of sodium phosphate dibasic anhydrous in water. If necessary, adjust with phosphoric acid to a pH of 7.6.

Solution B:

Mix 11 mL of 0.25 M sodium phosphate tribasic with 22 mL of 0.5 M sodium phosphate dibasic, and dilute with water to 100 mL.

Mobile phase:

Acetonitrile and Solution A (35:65)

Standard solution:

0.05 mg/mL of USP Omeprazole RS prepared as follows. Transfer 10 mg of USP Omeprazole RS to a 200-mL volumetric flask, and dissolve in 10 mL of methanol. Add 10 mL of Solution B, and dilute with water to volume.

Sample solution:

0.05 mg/mL of Omeprazole Magnesium prepared as follows. Transfer 10 mg of Omeprazole Magnesium to a 200-mL volumetric flask, and dissolve in 10 mL of methanol. Add 10 mL of Solution B, and dilute with water to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.0-mm × 12.5-cm or 4.6-mm × 15-cm; 5-µm packing L7.

[Note—Alternatively, a 3.9-mm × 15-cm column; 4-µm packing L1 may be used.]

Flow rate: 1.0 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

▲Tailing factor: NMT 1.5▲ (USP 1-May-2021)

Relative standard deviation: NMT ▲1.0%▲ (USP 1-May-2021)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of omeprazole magnesium (C₁₇H₁₉MgN₃O₃S₂) in the portion of Omeprazole Magnesium taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × [Mᵤ /(2 × Mₛ)] × 100

rᵤ = peak response of omeprazole 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 Magnesium in the Sample solution (mg/mL)

Mᵤ = molecular weight of omeprazole magnesium, 713.12

Mₛ = molecular weight of omeprazole, 345.42

Acceptance criteria: 97.5%–102.0% on the anhydrous basis

4 OTHER COMPONENTS

Content of Magnesium

Lanthanum solution:

Transfer 58.7 g of lanthanum oxide to a 1000-mL volumetric flask, wet the substance with some water, and dissolve by cautious addition of 250 mL of hydrochloric acid in 20- to 30-mL portions, cooling between the additions. Add water while stirring, cool to room temperature, and dilute with water to volume.

[Note—Store the solution in a plastic bottle.]

Standard stock solution:

1000 µg/mL of magnesium in water, from a commercially prepared atomic absorption standard solution.

[Note—Store the solution in a plastic bottle.]

Standard solution A:

Transfer 10.0 mL of Standard stock solution to a 500-mL volumetric flask, add 50 mL of 1 N hydrochloric acid, and dilute with water to volume. Transfer 20.0 mL of this solution to a 200-mL volumetric flask, and dilute with water to volume.

[Note—This solution contains 2 µg/mL of magnesium.]

Standard solution B:

Combine 5.0 mL of Standard solution A and 4.0 mL of Lanthanum solution, and dilute with water to 100.0 mL (0.1 µg/mL).

Standard solution C:

Combine 10.0 mL of Standard solution A and 4.0 mL of Lanthanum solution, and dilute with water to 100.0 mL (0.2 µg/mL).

Standard solution D:

Combine 15.0 mL of Standard solution A and 4.0 mL of Lanthanum solution, and dilute with water to 100.0 mL (0.3 µg/mL).

Standard solution E:

Combine 20.0 mL of Standard solution A and 4.0 mL of Lanthanum solution, and dilute with water to 100.0 mL (0.4 µg/mL).

Standard solution F:

Combine 25.0 mL of Standard solution A and 4.0 mL of Lanthanum solution, and dilute with water to 100.0 mL (0.5 µg/mL).

[Note—Concentrations of the Standard solutions and the Sample solution may be modified to fit the linear or working range of the instrument. When using instruments with a linear calibration graph, the number of Standard solutions can be reduced.]

Sample solution:

Transfer 250 mg of Omeprazole Magnesium to a 100-mL volumetric flask, add 20 mL of 1 N hydrochloric acid, swirl until dissolved, and dilute with water to volume. Allow to stand for 30 min. Transfer 10.0 mL of this solution to a 200-mL volumetric flask, and dilute with water to volume. Transfer 10.0 mL of the solution to another 100-mL volumetric flask, add 4.0 mL of Lanthanum solution, and dilute with water to volume.

Blank:

Transfer 4.0 mL of Lanthanum solution to a 100-mL volumetric flask, and dilute with water to volume.

Instrumental conditions

(See Atomic Absorption Spectroscopy 〈852〉.)

Mode: Atomic absorption spectrophotometry

Flame: Air–acetylene

Analytical wavelength: 285.2 nm

Analysis

Samples: Standard solution B, Standard solution C, Standard solution D, Standard solution E, Standard solution F, Sample solution, and Blank

Determine the concentration, Cᵤ, in µg/mL, of magnesium in the Sample solution using the calibration graph.

Calculate the percentage of magnesium in the portion of Omeprazole Magnesium taken:

Result = (Cᵤ / Cₛ) × [100/(100 − F)] × 100

Cᵤ = concentration of magnesium in the Sample solution as calculated above (µg/mL)

Cₛ = concentration of Omeprazole Magnesium in the Sample solution (µg/mL)

F = content of water in Omeprazole Magnesium, as determined in Specific Tests, Water Determination (%)

Acceptance criteria: 3.30%–3.55% of magnesium content on the anhydrous basis

5 IMPURITIES

Change to read:

Organic Impurities

Solution A: Prepare as directed in the Assay.

Mobile phase: Acetonitrile and Solution A (27.5:72.5) ▲

▲ (USP 1-May-2021)

[Note—To improve the resolution, the composition may be changed to 1:3, if necessary.]

System suitability solution:

0.04 mg/mL each of USP Omeprazole RS and USP Omeprazole Related Compound A RS in Mobile phase ▲

▲ (USP 1-May-2021)

Sample solution:

0.16 mg/mL of Omeprazole Magnesium in Mobile phase.

[Note—Prepare this solution fresh.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.0-mm × 12.5-cm or 4.6-mm × 15-cm; 5-µm packing L7.

[Note—Alternatively, a 3.9-mm × 15-cm column; 4-µm packing L1 may be used.]

Flow rate: 0.8–1.0 mL/min

Injection volume: 50 µL

Run time: NLT 4.5 times the retention time of omeprazole

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 3 between omeprazole related compound A and omeprazole

Analysis

Sample: Sample solution

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

Result = (rᵤ / rₜ) × 100

rᵤ = peak response of any individual impurity from the Sample solution

rₜ = sum of all the peak responses from the Sample solution

Acceptance criteria: See Table 1.

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

6 SPECIFIC TESTS

Water Determination 〈921〉, Method I: 7%–10%

Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 10 mg/mL, in methanol

Acceptance criteria: +0.5° to −0.5°, measured at 20°

Color of Solution

Analysis: Prepare a solution of Omeprazole Magnesium in methanol having a concentration of 20 mg/mL, and filter. Determine the absorbance of this solution at 440 nm, in 1-cm cells, using methanol as the blank.

Acceptance criteria: The absorbance is NMT 0.1.

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, protected from light. Store at room temperature.

USP Reference Standards 〈11〉

USP Omeprazole RS

USP Omeprazole Magnesium 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