Pantoprazole 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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C₁₆H₁₄F₂N₃NaO₄S · 3/2 _{(USP 1-Dec-2023)} H₂O           432.37

1H-Benzimidazole, 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulnyl]-, (USP 1-Dec-2023) sodium salt, hydrate (2:3); 5-(Diuoromethoxy)-2-[[(3,4-dimethoxy-2-pyridyl)methyl]sulnyl]benzimidazole, sodium salt, sesquihydrate   CAS RN®: 164579-32-2; UNII: 6871619Q5X. Anhydrous

C₁₆H₁₄F₂N₃NaO₄S           405.35 CAS RN®: 138786-67-1; UNII: S9363155XL.

Pantoprazole (free acid)

C₁₆H₁₅F₂N₃O₄S                383.37 CAS RN®: 102625-70-7; UNII: D8TST4O562. (USP 1-Dec-2023)

1 DEFINITION

Pantoprazole Sodium contains NLT 98.0% and NMT 102.0% of pantoprazole sodium (C₁₆H₁₄F₂N₃NaO₄S), calculated on the anhydrous basis.

2 IDENTIFICATION

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

B. 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:

C. Identification Tests—General 〈191〉, Chemical Identification Tests, Sodium: Meets the requirements  (USP 1-Dec-2023)

3 ASSAY

Change to read:

Procedure

[Note—Protect solutions containing pantoprazole sodium from light.]

Buffer: 1.32 g/L of dibasic ammonium phosphate in water, adjusted with phosphoric acid to a pH of 7.5

Solvent (USP 1-Dec-2023) mixture: Acetonitrile and methanol (70:30) (USP 1-Dec-2023)

Solution A: Solvent (USP 1-Dec-2023) mixture and Buffer (USP 1-Dec-2023) (15:85)

Solution B: Solvent (USP 1-Dec-2023) mixture

Mobile phase: See Table 1.  (USP 1-Dec-2023)

Table 1

Diluent 1: Acetonitrile and water (50:50) (USP 1-Dec-2023)

Diluent 2: (USP 1-Dec-2023) Dilute 25 mL of ammonium hydroxide with water to 500 mL.

(USP 1-Dec-2023)

Standard stock solution: 0.4 mg/mL of USP Pantoprazole Sodium RS prepared as follows. Transfer a suitable amount of USP Pantoprazole Sodium RS to a suitable volumetric flask containing 10%–20% of the final volume of Diluent 1, (USP 1-Dec-2023) and dilute with Diluent 2 (USP 1-Dec-2023) to volume.

Standard solution: 0.06 mg/mL of USP Pantoprazole Sodium RS from the Standard stock solution in Diluent 2 (USP 1-Dec-2023) Sample stock solution: 0.4 mg/mL of Pantoprazole Sodium prepared as follows. (USP 1-Dec-2023) Transfer about 20 mg of Pantoprazole Sodium to a 50-mL volumetric flask. Dissolve in Diluent 1 at 10%–20% of the nal volume, (USP 1-Dec-2023) and dilute with Diluent 2 (USP 1-Dec-2023) to volume.

Sample solution: 0.06 mg/mL of Pantoprazole Sodium from the Sample stock solution in Diluent 2 (USP 1-Dec-2023)

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 285 nm

Column: 3.9-mm × 15-cm; 4-µm packing L1

Temperatures

Autosampler: 4°

Column: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

3.2 System suitability

Sample:  (USP 1-Dec-2023) Standard solution

 (USP 1-Dec-2023)

Suitability requirements

Tailing factor: NMT 2.0 (USP 1-Dec-2023)

Relative standard deviation: NMT 0.73%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of pantoprazole sodium (C₁₆H₁₄F₂N₃NaO₄S) in the portion of Pantoprazole Sodium taken:

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

r_U = peak response of pantoprazole (USP 1-Dec-2023) from the Sample solution

r_S = peak response of pantoprazole (USP 1-Dec-2023) from the Standard solution

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

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

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

4 IMPURITIES

Change to read:

4.1 Organic Impurities

[Note—On the basis of the synthetic route, perform either Procedure 1 or Procedure 2. Procedure 2 is recommended when impurities C, D, E, and F are potential related compounds.] (USP 1-Dec-2023)

[Note—Protect solutions containing pantoprazole sodium from light.]

Procedure (USP 1-Dec-2023) 1

Buffer, (USP 1-Dec-2023) Mobile phase, Diluent 1, (USP 1-Dec-2023) Diluent 2, (USP 1-Dec-2023) Standard stock solution, Sample stock solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.0004 mg/mL of USP Pantoprazole Sodium RS from the Standard stock solution in Diluent 2 Sensitivity solution: 0.2 μg/mL of USP Pantoprazole Sodium RS from the Standard solution in Diluent 2 (USP 1-Dec-2023) Sample solution: Sample stock solution

4.1.1 System suitability

Samples:  (USP 1-Dec-2023) Standard solution and Sensitivity solution (USP 1-Dec-2023)

[Note—See Table 2 for the relative retention times.]

Suitability requirements

 (USP 1-Dec-2023)

Relative standard deviation: NMT 10.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution (USP 1-Dec-2023)

4.1.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any (USP 1-Dec-2023) impurity in the portion of Pantoprazole Sodium taken:

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

r_U = peak response of any (USP 1-Dec-2023) impurity from the Sample solution

r_S = peak response of pantoprazole from the Standard solution

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

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

Acceptance criteria: See Table 2. The reporting threshold (USP 1-Dec-2023) is 0.05%.

Table 2

4.2 Procedure (USP 1-Dec-2023) 2

Solution A: 1.74 g/L of dibasic potassium phosphate in water. (USP 1-Dec-2023) Adjust with a solution of phosphoric acid (330 g/L) to a pH of 7.0. (USP 1-Dec-2023)

Solution B: Acetonitrile

Mobile phase: See Table 3.  (USP 1-Dec-2023)

Table 3

Diluent: Acetonitrile and 0.001 N sodium hydroxide (50:50) (USP 1-Dec-2023)

System suitability solution: 0.46 mg/mL of USP Pantoprazole Sodium RS, and 1.3 µg/mL each of USP Pantoprazole Related Compound A RS, USP Pantoprazole Related Compound B RS, USP Pantoprazole Related Compound C RS, USP Pantoprazole Related Compounds D and F Mixture RS, and USP Pantoprazole Related Compound E RS in Diluent

Standard solution: 0.03 mg/mL of USP Pantoprazole Sodium RS in Diluent

Sensitivity solution: 0.2 μg/mL of USP Pantoprazole Sodium RS from the Standard solution in Diluent (USP 1-Dec-2023) Sample solution: 0.46 mg/mL of Pantoprazole Sodium in Diluent

4.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 290 and 305 nm

Column: 4.0-mm (USP 1-Dec-2023) × 12.5-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 20 µL

4.2.2 System suitability

Samples: System suitability solution, Standard solution (at 290 nm), and Sensitivity solution (at 290 nm) (USP 1-Dec-2023) [Note—See Table 4 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between pantoprazole related compound E and pantoprazole related compounds D and F, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution (USP 1-Dec-2023)

4.2.3 Analysis

[Note—Pantoprazole related compound C is monitored at 305 nm, and all other compounds are monitored at 290 nm.]

Samples: Standard solution and Sample solution

Calculate the percentage of any (USP 1-Dec-2023) impurity in the portion of Pantoprazole Sodium taken:

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

r_U = peak response of any (USP 1-Dec-2023) impurity from the Sample solution

r_S = peak response of pantoprazole  (USP 1-Dec-2023) from the Standard solution

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

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

F = relative response factor (see Table 4)

Acceptance criteria: See Table 4.  (USP 1-Dec-2023) The reporting threshold (USP 1-Dec-2023) is 0.05%.

Table 4

a At 305 nm.

b Impurities D and F are not fully resolved and should be integrated together.

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I: 4.5%–8.0%

Add the following:

Bacterial Endotoxins Test 〈85〉: Where the label states that Pantoprazole Sodium must be subjected to further processing during the preparation of injectable dosage forms, the level of bacterial endotoxins are such that the requirement under the relevant dosage form monograph(s) in which Pantoprazole Sodium is used can be met. (USP 1-Dec-2023)

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, light-resistant containers. Store at room temperature.

Change to read:

Labeling: If a test for Organic Impurities other than Procedure (USP 1-Dec-2023) 1 is used, then the labeling states the test with which the article complies. Where it is intended for use in preparing injectable dosage forms, the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms. (USP 1-Dec-2023)

Change to read:

USP Reference Standards 〈11〉

USP Pantoprazole Sodium RS

USP Pantoprazole Related Compound A RS

5-(Diuoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfonyl]-1H-benzimidazole. (USP 1-Dec-2023)

C₁₆H₁₅F₂N₃O₅S           399.37

USP Pantoprazole Related Compound B RS

5-(Diuoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylthio]-1H-benzimidazole. (USP 1-Dec-2023)

C₁₆H₁₅F₂N₃O₃S           367.37

USP Pantoprazole Related Compound C RS

5-(Diuoromethoxy)-1H-benzimidazole-2-thiol.

C₈H₆F₂N₂OS              216.21

USP Pantoprazole Related Compounds D and F Mixture RS

Contains a mixture of the following two compounds:

5-(Diuoromethoxy)-2-[(RS)-[(3,4-dimethoxypyridin-2-yl)methyl]sulnyl]-1-methyl-1H-benzimidazole;

6-(Diuoromethoxy)-2-[(RS)-[(3,4-dimethoxypyridin-2-yl)methyl]sulnyl]-1-methyl-1H-benzimidazole.

C₁₇H₁₇F₂N₃O₄S     397.40

USP Pantoprazole Related Compound E RS

6,6′-Bis(diuoromethoxy)-2,2′-bis[[(3,4-dimethoxypyridin-2-yl)methyl]sulnyl]-1H,1′H-5,5′-bibenzimidazole.

C₃₂H₂₈F4N₆O₈S₂     764.72