Lansoprazole

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

C₁₆H₁₄F₃N₃O₂S 369.36

1H-Benzimidazole, 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-;

2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]-methyl]sulfinyl]benzimidazole CAS RN®: 103577-45-3; UNII: 0K5C5T2QPG.

1 DEFINITION

Lansoprazole contains NLT 98.0% and NMT 102.0% of C₁₆H₁₄F₃N₃O₂S.

2 IDENTIFICATION

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

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Sample solution: 10 μg/mL in methanol

Acceptance criteria: Meets the requirements

3 ASSAY

Procedure

Mobile phase: Acetonitrile, water, and triethylamine (40:60:1). Adjust with phosphoric acid to a pH of 7.0.

Diluent: Acetonitrile, water, and triethylamine (40:60:1). Adjust with phosphoric acid to a pH of 10.0.

System suitability solution: 0.1 mg/mL of USP Lansoprazole RS and 0.1 mg/mL of USP Lansoprazole Related Compound A RS in Diluent

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

Sample solution: 0.1 mg/mL of Lansoprazole in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 285 nm

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

Flow rate: 1 mL/min

Injection size: 10 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 5 between lansoprazole and lansoprazole related compound A, System suitability solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of lansoprazole (C₁₆H₁₄F₃N₃O₂S) in the portion of Lansoprazole taken:

Result = (r_U/r_S)x(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 Lansoprazole RS in the Standard solution (mg/mL)

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

Acceptance criteria: 98.0%–102.0%

4 IMPURITIES

Inorganic Impurities

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Procedure

[Note—Store and inject the lansoprazole solutions at or below 5° using a cooled autosampler. The solutions are stable for about 24 h when

stored at 5°.]

Solution A: Water

Solution B: Acetonitrile, water, and triethylamine (160:40:1). Adjust with phosphoric acid to a pH of 7.0.

Diluent: Methanol and 0.1 N sodium hydroxide (1:3)

Mobile phase: See Table 1.

Table 1

System suitability solution: Prepare a solution containing 25 μg/mL of USP Lansoprazole RS and 25 μg/mL of USP Lansoprazole Related Compound A RS in methanol. Transfer 1 mL of this solution into a 10-mL volumetric flask, and dilute with Diluent to volume.

Standard solution: Prepare a solution containing 25 μg/mL of USP Lansoprazole RS and 25 μg/mL of USP Lansoprazole Related

Compound B RS in methanol. Transfer 1 mL of this solution into a 100-mL volumetric flask, and dilute with Diluent to volume.

Sample solution: 2.5 mg/mL of Lansoprazole in methanol. Transfer 1 mL of this solution into a 10-mL volumetric flask, and dilute with Diluent to volume.

Blank: Methanol and Diluent (1:9)

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 285 nm

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

Flow rate: 0.8 mL/min

Injection size: 40 μL

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 6 between lansoprazole and lansoprazole related compound A

Relative standard deviation: NMT 3%

Analysis

Samples: Standard solution, Sample solution, and Blank

Identify the lansoprazole peak and the peaks due to the impurities listed in Table 2. Measure the areas for the major peaks, excluding

peaks obtained from the Blank.

Calculate the percentage of lansoprazole related compound B in the portion of Lansoprazole taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak response for lansoprazole related compound B from the Sample solution

r_S = peak response for lansoprazole related compound B from the Standard solution

C_S = concentration of USP Lansoprazole Related Compound B RS in the Standard solution (μg/mL)

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

Calculate the percentage of lansoprazole N-oxide, lansoprazole sulfone, and any other individual impurity in the portion of Lansoprazole taken:

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

r_U = peak response for each impurity from the Sample solution

r_S = peak response for lansoprazole from the Standard solution

C_S = concentration of USP Lansoprazole RS in the Standard solution (μg/mL)

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

F = relative response factor for each impurity (see Table 2)

Acceptance criteria

Individual impurities: See Table 2. Disregard any peak below 0.05%.

Table 2

^a [[(1H-Benzimidazole-2-yl)sulfinyl]methyl]-3-methyl-4-(2,2,2-trifluoroethoxy)-pyridine 1-oxide.

^b 2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfonyl]benzimidazole.

^c 2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-pyridin-2-yl]methyl]sulfanyl]-1H-benzimidazole.

5 SPECIFIC TESTS

Water Determination, Method Ia〈921〉

Sample: 1.0 g

[Note—Use 50 mL of a dehydrated mixture of pyridine and ethylene glycol (9:1 to 8:2) as the solvent.]

Acceptance criteria: NMT 0.1%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at room temperature, and protect from excessive heat.

Change to read:

USP Reference Standards 〈11〉

USP Lansoprazole RS

USP Lansoprazole Related Compound A RS

2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfonyl]benzimidazole.

C₁₆H₁₄F₃N₃O₃S 385.36

USP Lansoprazole Related Compound B RS

2-{[(3-Methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl)methyl]thio}benzimidazole monohydrate.

C₁₆H₁₄F₃N₃OS · H₂O 371.38 (ERR 1-Jul-2021)