Rabeprazole Sodium

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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C₁₈H₂₀N₃NaO₃S (anhydrous) 381.42

C₁₈H₂₀N₃NaO₃S · xH₂O (hydrated form)

1H-Benzimidazole, 2-({[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl}sulfinyl)-, sodium salt;

2-({[4-(3-Methoxypropoxy)-3-methylpyridin-2-yl]methyl}sulfinyl)benzimidazole sodium salt CAS RN^®: 117976-90-6; UNII: 3L36P16U4R.

1 DEFINITION

Rabeprazole Sodium contains NLT 98.0% and NMT 102.0% of rabeprazole sodium (C₁₈H₂₀N₃NaO₃S), calculated on the dried basis. The hydrated form contains NLT 98.0% and NMT 102.0% of rabeprazole sodium (C₁₈H₂₀N₃NaO₃S), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

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

[Note-If the spectra obtained in the solid state shows differences, dissolve the substance to be examined and the reference substance separately in methanol, evaporate to dryness, and record new spectra using the residues.]

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

C. Identification Tests-General 〈191〉, Chemical Identification Tests, Sodium: Meets the requirements

3 ASSAY

Change to read:

3.1 Procedure

[Note-Protect solutions containing rabeprazole from light.]

Buffer 1: 4.35 g/L of dibasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 7.0.

Buffer 2: Dissolve 17.4 g of dibasic potassium phosphate in 950 mL of water, adjust with 2 N potassium hydroxide to a pH of 11.3, and dilute with water to 1000 mL. Pass through a suitable filter of 0.45-µm pore size.

Solution A: Acetonitrile and Buffer 1 (5:95)

Solution B: Methanol

Solution C: Acetonitrile

Mobile phase: See Table 1.

Table 1

Return to original conditions and re-equilibrate the system for 10 min.

Diluent: Methanol and Buffer 2 (20:80)

Standard solution: 0.1 mg/mL of USP Rabeprazole Sodium RS in Diluent

Sample solution: 0.1 mg/mL of Rabeprazole Sodium in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Temperatures

Autosampler: 6°

Column: 45°

Flow rate: 1 mL/min

Injection volume: 5 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of rabeprazole sodium (C₁₈H₂₀N₃NaO₃S) in the portion of Rabeprazole Sodium taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

C_U = concentration of Rabeprazole Sodium in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the dried basis for the anhydrous form or on the anhydrous basis for the hydrated form

4 IMPURITIES

Change to read:

4.1 Organic Impurities

[Note-Protect solutions containing rabeprazole from light.]

Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 1.0 mg/mL of USP Rabeprazole Sodium RS and 0.002 mg/mL each of USP Rabeprazole Related Compound A RS, USP Rabeprazole Related Compound B RS, USP Rabeprazole Related Compound C RS, USP Rabeprazole Related Compound D RS, USP Rabeprazole Related Compound E RS, and USP Rabeprazole Related Compound F RS in Diluent

Sensitivity solution: 0.5 µg/mL of USP Rabeprazole Sodium RS in Diluent

Standard solution: 0.001 mg/mL of USP Rabeprazole Sodium RS in Diluent

Sample solution: 1.0 mg/mL of Rabeprazole Sodium in Diluent

System suitability

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

Suitability requirements

Peak-to-valley ratio: NLT 1.5 for rabeprazole related compound F and rabeprazole, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Rabeprazole Sodium taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of rabeprazole from the Standard solution

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

C_U = concentration of Rabeprazole Sodium in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

ᵃ 1H-Benzimidazol-2-ol.

ᵇ 2-{[(1H-Benzimidazol-2-yl)sulfonyl]methyl}-4-(3-methoxypropoxy)-3-methylpyridine 1-oxide.

ᶜ 2-{[(4-Methoxy-3-methylpyridin-2-yl)methyl]sulfinyl}benzimidazole.

ᵈ 2-{[(4-Methoxy-3-methylpyridin-2-yl)methyl]thio}benzimidazole.

5 SPECIFIC TESTS

5.1 Loss on Drying 〈731〉

[Note-Perform this test for the anhydrous form.]

Analysis: Dry under vacuum over phosphorus pentoxide for 24 h.

Acceptance criteria: NMT 1.0%

5.2 Water Determination 〈921〉, Method I

[Note-Perform this test where it is labeled as a hydrated form.]

[Note-Hydranal Composite 5 is a suitable titrant.]

Sample: 0.2 g

Acceptance criteria: NMT 7.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at room temperature.

Labeling: Where it is the hydrated form, the label so indicates.

Change to read:

USP Reference Standards 〈11〉

USP Rabeprazole Sodium RS

USP Rabeprazole Related Compound A RS

[Note-May be available as monosodium or disodium salt.]

Sodium 1-(1H-benzimidazol-2-yl)-3-methyl-4-oxo-1,4-dihydropyridine-2-carboxylate.

C₁₄H₁₀N₃NaO₃ 291.24

Disodium 1-(1H-benzimidazol-2-yl)-3-methyl-4-oxo-1,4-dihydropyridine-2-carboxylate.

C₁₄H₉N₃Na₂O₃ 313.22

USP Rabeprazole Related Compound B RS

2-{[(1H-Benzimidazol-2-yl)sulfinyl]methyl}-4-(3-methoxypropoxy)-3-methylpyridine 1-oxide.

C₁₈H₂₁N₃O₄S 375.44

USP Rabeprazole Related Compound C RS

1H-Benzimidazole-2-thiol.

C₇H₆N₂S 150.20

USP Rabeprazole Related Compound D RS

2-({[4-(3-Methoxypropoxy)-3-methyl-2-pyridyl]methyl}sulfonyl)benzimidazole.

C₁₈H₂₁N₃O₄S 375.44

USP Rabeprazole Related Compound E RS

2-{[4-(3-Methoxypropoxy)-3-methyl-2-pyridyl]methylthio}benzimidazole.

C₁₈H₂₁N₃O₄S 343.44

USP Rabeprazole Related Compound F RS

2-{[(4-Chloro-3-methyl-2-pyridyl)methyl]sulfinyl}benzimidazole.

C₁₄H₁₂ClN₃OS 305.78