Esomeprazole Strontium

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1H-Benzimidazole, 5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulnyl], strontium salt, hydrate (2:1:4);

(−)-5-Methoxy-2-{(S)-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulnyl}-1H-benzimidazole strontium salt tetrahydrate CAS RN®: 934714-36-0.

1 DEFINITION

Esomeprazole Strontium contains NLT 98.0% and NMT 102.0% of esomeprazole strontium (C₃₄H₃₆N₆O₆S₂Sr), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A OR 197K (CN 1-MAY-2020) O(1974).

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.

Sample solution: 1 mg/mL of Esomeprazole Strontium in 20% acetonitrile (v/v)

Acceptance criteria: The Sample solution imparts a red color to the nonluminous flame.

3 ASSAY

PROCEDURE

Buffer: Dissolve 1.12 g of dibasic sodium phosphate anhydrous and 0.18 g of monobasic sodium phosphate anhydrous in 1000 ml of water.

If necessary, adjust with phosphoric acid to a pH of 7.6.

Solution A: Acetonitrile and Buffer (10:30)

Solution B: Acetonitrile and Buffer (20:30)

Mobile phase: See Table 1

Return to the original conditions, and re-equilibrate the system for about 5 min.

System suitability solution: 0.5 mg/mL of USP Omeprazole RS and 0.5 µg/mL of USP Omeprazole Related Compound A RS in Solution A

Standard solution: 0.5 mg/mL of USP Omeprazole BS in Solution A

Sample solution: 0.5 mg/mL of Esomeprazole Strontium in Solution A

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 280 nm

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

Column temperature: 30

Flow rate: 1 mL/min

Injection volume: 5 l

System suitability

Samples: Syntem suitability solution and Standard solution

Suitability requirements

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

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of esomeprazole strontium (C₃₄H₃₆N₆O₆S₂Sr) in the portion of Esomeprazole Strontium taken

Result = (r_U/(r_S) × (C_S /C_U) x [M_r1 /(2 × M_r2 )] × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

C_U = concentration of Esomeprazole Strontium in the Sample solution (mg/mL)

M_r1 = molecular weight of esomeprazole strontium, 776.44

M_r2 = molecular weight of omeprazole 345.42

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

4 OTHER COMPONENTS

CONTENT OF STRONTIUM

Solution A: 37.2 mg/ml. of edetate sodium in water

Solution B: 249 mg/ml of cuenc sulfate in water

Solution C: Solution A and Solution B (1:1)

Buffer: Transfer 54 g of ammonium chloride to a 1000-mi, volumetric flask, add 350 ml of ammonium hydroxide, and dilute with water to volume

OFICIAL Analysis: Transfer the Sample to a suitable flask, dissolve in 30 mL of methanol, add 40 mL of Buffer, and mix. Add 0.5 mL of phi 7.0 phosphate buffer and 1 ml of Solution C, and mix. Titrate with 0.05 M edetate dipodium VS to a potentiometric endpoint (see Titrimetre (5411). Perform a blank determination. Each mL of 0.05 Medetate disodium VS is equivalent to 4.381 mg of strontium

Sample: 400 mg of Esomeprazole Strontium

Acceptance criteria: 10.8-11.8% on the dried basis

5 IMPURITIES

ORGANIC IMPURITIES

Buffer, Solution A, Solution B, Mobile phase, and Chromatographic system: Proceed as directed in the Assay

System suitability solution: 500 µg/ml, of (SP Omennazole RS and 0.5 µg/ml. of USP Omeprazole Related Compound A RS in Solution A

Standard solution: 0.5 µg/ml each of USP Omeprazole RS and USP Omeprazole Related Compound A.RS and 0.25 µg/ml of (bing in

Solution A

Sample solution: 500 µg/ml of Esomeprazole Strontium in Solution A

System suitability

Samples: Systern suitability solution and Standard solution

Not See Table 2 for relative retention times.

Suitability requiremente

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

Relative standard deviation: NMT 10% for each peak, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentages of omeprazole related compound A and (5)-binol in the portion of Esomeprazole Strontium taken:

Result = (r_U/(r_S) × (C_S /C_U) x 100

r_U = peak response of omeprazole related compound A or (S)-binol from the Sample solution

r_S = peak response of omeprazole related compound A or (S)-binol from the Standard solution

C_S = concentration of USP Omeprazole Related Compound A RS or (S)-binol in the Standard solution (μg/mL)

C_U = concentration of Esomeprazole Strontium in the Sample solution (μg/mL)

Calculate the percentage of each unspecified impurity in the portion of Esomeprazole Strontium taken:

Result = (r_U/(r_S) x 100

r_U = peak response of each unspecified impurity from the Sample solution

r_S = sum of all peak responses from the Sample solution

Acceptance criteria: See Table 2. Disregard any impurity peaks less than 0.05%

^a 1-(2-Hydroxynaphthalen-1-yl)naphthalene-2-ol.

ENANTIOVERC PURITY

Solution A: Dissolve 1.42 g of dibasic sodium phosphate anhydrous in 500 ml, of water. Adjust with phoachoric acid to a pH of 6.5 and dilute with water to 1000 ml.

Solution B: Acetonitrile

Mobile phase: See Table 3

Return to the original conditions, and re-equilibrate the system for about 5 min

Buffer: Prepare as directed in the Assay.

System suitability solution: 0.005 mg/mL of USP Omeprazole RS in Diluent

Sample solution: 0.5 mg/mL of Esomeprazole Strontium in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.0-mm × 15-cm; 5-μm packing L41

Column temperature: 30°

Flow rate: 0.8 mL/min

Injection volume: 5 μL

Run time: 4 times the retention time of esomeprazole

System suitability

[Note—The elution order is the R-enantiomer, followed by the esomeprazole peak, which is the S-enantiomer.]

Sample: System suitability solution

Suitability requirements

Resolution: NLT 5 between the esomeprazole and R-enantiomer peaks

Relative standard deviation: NMT 10% for each peak

Analysis

Sample: Sample solution

Calculate the percentage of each unspecified impurity in the portion of Esomeprazole Strontium taken:

Result = (r_U/(r_S) x 100

r_U = peak response of each unspecified impurity from the Sample solution

r_S = sum of all peak responses from the Sample solution

Acceptance criteria: NMT 0.1% of the R-enantiomer

6 SPECIFIC TESTS

Loss ON DAVING (731)

Analysis: Dry at 125° to constant weight.

Acceptance criteria: 7.5%-9.5%

COLOR OF SOLUTION

Sample solution: 20 mg/mL of Esomeprazole Strontium in acetone

Analysis: Determine the absorbance of the Sample solution at 440 and 650 nm, in 1-cm cells, using acetone as the blank.

Acceptance criteria: NMT 0.2 at 440 and 650 nm

7 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers protected from light.