Pantoprazole Sodium Delayed-Release Tablets

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

1 DEFINITION

Pantoprazole Sodium Delayed-Release Tablets contain an amount of Pantoprazole Sodium equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S).

2 IDENTIFICATION

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

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

3 ASSAY

3.1 PROCEDURE

Dilute ammonium hydroxide: Ammonium hydroxide and water (50:50)

Buffer: 3.85 g/L of ammonium acetate and 1.1 g/L of tetrabutylammonium hydrogen sulfate in water. Adjust with Dilute ammonium hydroxide to a pH of 7.9.

Mobile phase: Acetonitrile and Buffer (35:65)

Diluent: Acetonitrile and 0.02 N sodium hydroxide (50:50)

System suitability solution: 0.2 mg/mL of USP Pantoprazole Sodium RS and 0.0004 mg/mL each of USP Pantoprazole Related Compound A RS and USP Pantoprazole Related Compound B RS in 0.02 N sodium hydroxide. Sonicate to dissolve, if necessary.

Standard solution: 0.2 mg/mL of USP Pantoprazole Sodium RS prepared as follows. Transfer a suitable amount of USP Pantoprazole Sodium RS to a suitable volumetric flask, add 0.02 N sodium hydroxide to about 60% of the final volume and sonicate for about 5 min to dissolve. To this solution add about 2% of the final volume of acetonitrile, and dilute with 0.02 N sodium hydroxide to volume.

Sample solution: Nominally 0.2 mg/mL of pantoprazole from Tablets prepared as follows. Transfer 5 Tablets to a suitable volumetric flask. [NOTE-Use 50- or 100-mL volumetric flasks for Tablets containing 20 or 40 mg of pantoprazole per Tablet, respectively.] Add Diluent to about 60% of the final volume, shake mechanically for about 60 min, and dilute with Diluent to volume. Pass through a suitable filter, and dilute the filtrate with 0.02 N sodium hydroxide to obtain a solution having a known concentration of about 0.2 mg/mL, based on the label claim.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 290 nm. For Identification B, use a diode array detector in the range of 200-400 nm.

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

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 3 times the retention time of pantoprazole

3.3 System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 3 between pantoprazole and pantoprazole related compound A, System suitability solution

Tailing factor: NMT 2.0 for pantoprazole, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of pantoprazole (C₁₆H₁₅F₂N₃O₄S) in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x (M_r1/M_r2) x 100

r_U = peak response of pantoprazole 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 = nominal concentration of pantoprazole in the Sample solution (mg/mL)

M_r1 = molecular weight of pantoprazole, 383.37

M_r2 = molecular weight of pantoprazole sodium, 405.35

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 DISSOLUTION (711)

4.1.1 Test 1: Proceed as directed for Dissolution (711), Procedure, Apparatus 1 and Apparatus 2, Delayed-Release Dosage Forms, Method B Procedure.

Acid stage

Acid stage medium: 0.1 N hydrochloric acid; 1000 mL

Apparatus 2: 75 rpm

Time: 120 min

Mobile phase: Acetonitrile, triethylamine, and water (40:1:60). Adjust with phosphoric acid to a pH of 7.0 ± 0.05.

Diluent: pH 6.8 phosphate buffer and 0.5 N sodium hydroxide (50:50)

Standard stock solution: 0.4 mg/mL of USP Pantoprazole Sodium RS prepared as follows. Transfer about 20 mg of USP Pantoprazole Sodium RS to a 50-mL volumetric flask. Add about 30 mL of 0.02 N sodium hydroxide, and sonicate until dissolved. Add 2 mL of acetonitrile, and dilute with 0.02 N sodium hydroxide to volume.

Standard solution: 0.02 mg/mL of USP Pantoprazole Sodium RS from the Standard stock solution in Diluent

Sample solution: After 120 min pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, and immediately dilute a portion of the filtrate by a factor of 2 with 0.5 N sodium hydroxide. Transfer the Tablets to the vessels containing the Buffer stage medium.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 290 nm

Column: 4.6-mm x 7.5-cm; 3-µm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 3 times the retention time of pantoprazole

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) dissolved in the Acid stage:

Result = (r_U/r_S) x C_S x V x D x (M_r1/M_r2) x (1/L) x 100

r_U = peak response of pantoprazole 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)

V = volume of Acid stage medium, 1000 mL

D = dilution factor for the Sample solution, 2

M_r1 = molecular weight of pantoprazole, 383.37

M_r2 = molecular weight of pantoprazole sodium, 405.35

L = label claim (mg/Tablet)

Tolerances: NMT 10% of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) is dissolved.

Buffer stage

Buffer stage medium: pH 6.8 phosphate buffer; 1000 mL

Apparatus 2: 75 rpm

Time: 30 min

Standard solution: Prepared as directed in the Acid stage.

Sample solution: After 30 min, pass a portion of the sample solution under test through a suitable filter of 0.45-µm pore size and immediately dilute a portion of the filtrate by a factor of 2 with 0.5 N sodium hydroxide.

Chromatographic system: Proceed as directed in the Acid stage.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) dissolved:

Result = (r_U/r_S) x C_S x V x D x (M_r1/M_r2) x (1/L) x 100

r_U = peak response of pantoprazole 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)

V = volume of Buffer stage medium, 1000 mL

D = dilution factor for the Sample solution, 2

M_r1 = molecular weight of pantoprazole, 383.37

M_r2 = molecular weight of pantoprazole sodium, 405.35

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) is dissolved.

4.1.2 Test 2: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2. Proceed as directed for Dissolution (711), Procedure, Apparatus 1 and Apparatus 2, Delayed-Release Dosage Forms, Method B Procedure.

Acid stage

Acid stage medium: 0.1 N hydrochloric acid: 1000 mL

Apparatus 2: 100 rpm

Time: 2 h

Standard stock solution: 0.46 mg/mL of USP Pantoprazole Sodium RS prepared as follows. Transfer a quantity of USP Pantoprazole Sodium RS to a suitable volumetric flask. Dissolve first in 0.1 N sodium hydroxide, using 10% of the final volume, then dilute with pH 6.8 phosphate buffer to volume. Mix well until a clear solution is obtained.

Acid stage standard solution: (L/10000) (ERR 1-Dec-2023) mg/mL of USP Pantoprazole Sodium RS from the Standard stock solution in Acid stage medium, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter of 10-µm pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: UV 305 nm

Path length: 4 cm

Blank: Acid stage medium

Analysis

Samples: Acid stage standard solution and Sample solution

Calculate the percentage of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) dissolved in the Acid stage:

Result = (A_U/A_S) x C_S x V x (M_r1/M_r2) x (1/L) x 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Acid stage standard solution

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

V = volume of Acid stage medium, 1000 mL

M_r1 = molecular weight of pantoprazole, 383.37

M_r2 = molecular weight of pantoprazole sodium, 405.35

L = label claim (mg/Tablet)

Tolerances: NMT 10% of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) is dissolved.

Buffer stage

Buffer stage medium: pH 6.8 phosphate buffer; 1000 mL

Apparatus 2: 100 rpm

Time: 45 min

Standard stock solution: Prepare as directed in the Acid stage.

Buffer stage standard solution: (L/1000) mg/mL (ERR 1-Dec-2023) of USP Pantoprazole Sodium RS from the Standard stock solution in Buffer stage medium, (ERR 1-Dec-2023) where L is the label claim in mg/Tablet

Sample solution: After 2 h in Acid stage medium, continue with Buffer stage medium as follows. Completely drain the vessel of Acid stage medium carefully and add Buffer stage medium. After 45 min, pass a portion of the solution under test through a suitable filter of 10-µm pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: UV 288 nm

Path length: 0.5 cm

Blank: Buffer stage medium

Analysis

Samples: Buffer stage standard solution and Sample solution

Calculate the percentage of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) dissolved:

Result = (A_U/A_S) x C_S x V x (M_r1/M_r2) x (1/L) x 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Buffer stage standard solution

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

V = volume of the Buffer stage medium, 1000 mL

M_r1 = molecular weight of pantoprazole, 383.37

M_r2 = molecular weight of pantoprazole sodium, 405.35

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) is dissolved.

4.1.3 Test 3: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 3. Proceed as directed for Dissolution (711), Procedure, Apparatus 1 and Apparatus 2. Delayed-Release Dosage Forms, Method B Procedure.

Acid stage

Acid stage medium: 0.1 N hydrochloric acid; 1000 mL

Apparatus 2: 100 rpm

Time: 2 h

Dilute ammonia solution: Transfer 40 mL of strong ammonia solution to a 100-mL volumetric flask, and dilute with water to volume.

Buffer: 1.5 g/L of ammonium acetate in water. Adjust with Dilute ammonia solution to a pH of 7.0.

Mobile phase: Methanol and Buffer (40:60)

Acid stage standard solution: 0.4 mg/mL of USP Pantoprazole Sodium RS prepared as follows. Transfer a suitable quantity of USP Pantoprazole Sodium RS to a suitable volumetric flask, add 10% of the final volume of methanol, sonicate, and dilute with Mobile phase to volume.

Sample solution: 0.4 mg/mL of pantoprazole prepared as follows. After 2 h in the Acid stage medium, completely drain the vessel of Acid stage medium carefully, remove the Tablet from the vessel, and dry it with tissue paper. Transfer the Tablet to a suitable volumetric flask, add 20% of the final volume of methanol, and sonicate for about 20 min. Dilute with Mobile phase to volume. Mix well, centrifuge, and use the supernatant.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 290 nm

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

Autosampler temperature: 4°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Sample: Acid stage standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation : NMT 2.0%

Analysis

Samples: Acid stage standard solution and Sample solution

Calculate the percentage of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) dissolved in the Acid stage:

Result = A - [(r_U/r_S) x C_S x (M_r1/M_r2) x (1/L) x 100]

A = percentage of pantoprazole as determined in the Assay

r_U = peak response of pantoprazole from the Sample solution

r_S = peak response of pantoprazole from the Acid stage standard solution

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

M_r1 = molecular weight of pantoprazole, 383.37

M_r2 = molecular weight of pantoprazole sodium, 405.35

L = label claim (mg/Tablet)

Tolerances: NMT 10% of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) is dissolved.

Buffer stage

Buffer stage medium: pH 6.8 phosphate buffer; 1000 mL

Apparatus 2: 100 rpm

Time: 45 min

Buffer stage standard solution: (L/1000) mg/mL of USP Pantoprazole Sodium RS from the Acid stage standard solution in Buffer stage medium, where L is the label claim in mg/Tablet

Sample solution: Proceed as directed in the Acid stage with a new set of Tablets. After 2 h, proceed with Buffer stage medium as follows. Completely drain the vessel of Acid stage medium carefully and add the Buffer stage medium. After 45 min, withdraw 10 mL of the solution under test, and pass it through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 290 nm

Column: 4.6-mm x 25-cm; 5-µm packing 11

Autosampler temperature: 4°

Flow rate: 1 mL/min

Injection volume: 50 µL

Analysis

Samples: Buffer stage standard solution and Sample solution

Calculate the percentage of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) dissolved:

Result = (r_U/r_S) x C_S x V x (M_r1/M_r2) x (1/L) x 100

r_U = peak response of pantoprazole from the Sample solution

r_S = peak response of pantoprazole from the Buffer stage standard solution s

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

V = volume of Buffer stage medium, 1000 mL

M_r1 = molecular weight of pantoprazole, 383.37

M_r2 = molecular weight of pantoprazole sodium, 405.35

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) is dissolved.

4.1.4 Test 4: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 4. Proceed as directed for Dissolution (711), Procedure, Apparatus 1 and Apparatus 2, Delayed-Release Dosage Forms, Method B Procedure.

Acid stage

Acid stage medium: 0.1 N hydrochloric acid: 1000 mL, degassed

Apparatus 2: 100 rpm, with sinkers

Time: 2 h

Buffer

0.77 g/L of ammonium acetate in water. Adjust with acetic acid or ammonium hydroxide to a pH of 8.5 ± 0.1.

Solution A: Acetonitrile and Buffer (30:70)

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water and (30:70)

System suitability solution: 0.23 mg/mL of USP Pantoprazole Sodium RS and 6.8 µg/mL of USP Pantoprazole Related Compound A RS in

Diluent

Acid stage standard solution: 0.23 mg/mL of USP Pantoprazole Sodium RS in Diluent

Sample solution: Nominally 0.2 mg/mL of pantoprazole prepared as follows. After 2 h in the Acid stage medium, carefully remove the Tablet from the vessel and transfer to a suitable volumetric flask. Add 50% of the final volume of Diluent, and sonicate for about 20 min, but NMT about 60 min, swirling the flask every few minutes. Dilute with Diluent to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 290 nm

Column: 3.9-mm x 15-cm; 5-µm packing L1

Temperatures

Autosampler: 4°

Column: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Acid stage standard solution

Suitability requirements

Resolution: NLT 1.5 between pantoprazole related compound A and pantoprazole, System suitability solution

Relative standard deviation: NMT 2.0%, Acid stage standard solution

Analysis

Samples: Acid stage standard solution and Sample solution

Calculate the percentage of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) dissolved in the Acid stage:

Result = A - [(r_U/r_S) x C_S x (1/L) x (M_r1/M_r2) x 100]

A = percentage of pantoprazole as determined in the Assay

r_U = peak response of pantoprazole from the Sample solution

r_S = peak response of pantoprazole from the Acid stage standard solution

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

L = label claim (mg/Tablet)

M_r1 = molecular weight of pantoprazole, 383.37

M_r2 = molecular weight of pantoprazole sodium, 405.35

Tolerances: NMT 10% (Q) of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) is dissolved.

Buffer stage

Buffer stage medium: 76.0 g/L of tribasic sodium phosphate dodecahydrate in water. Add 250 mL of this solution to 750 mL of Acid stage medium, adjust with hydrochloric acid or sodium hydroxide to a pH of 6.80 ± 0.05; 1000 mL, degassed.

Apparatus 2: 100 rpm, with sinkers

Time: 45 min

Buffer stage standard stock solution: 1.6 mg/mL of USP Pantoprazole Sodium RS in methanol

Buffer stage standard solution: L/1000 mg/mL of USP Pantoprazole Sodium RS RS from the Buffer stage standard stock solution in Buffer stage medium, where L is the label claim in mg/Tablet

Sample solution: Transfer a Tablet with the sinker to the vessel containing Acid stage medium, and proceed as directed for the Acid stage. After 2 h, continue with Buffer stage medium as follows. Completely drain the Acid stage medium carefully and add the Buffer stage medium. After 45 min, withdraw 10 mL of the solution under test, and pass it through a suitable filter of 0.45-µm pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: UV 289 nm

Blank: Buffer stage medium

Analysis

Samples: Buffer stage standard solution and Sample solution

Calculate the percentage of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) dissolved:

Result = (A_U/A_S) x C_S x V x (M_r1/M_r2) × (1/L) x 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Buffer stage standard solution

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

V = volume of Buffer stage medium, 1000 mL

M_r1 = molecular weight of pantoprazole, 383.37

M_r2 = molecular weight of pantoprazole sodium, 405.35

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) is dissolved.

4.1.5 Test 5: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 5. Proceed as directed for Dissolution (711), Procedure, Apparatus 1 and Apparatus 2. Delayed-Release Dosage Forms, Method B Procedure.

Acid stage

Acid stage medium: 0.1 N hydrochloric acid; 900 mL, degassed

Apparatus 1: 100 rpm

Time: 2 h

Buffer: 8.77 g/L of dibasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 8.0.

Diluent: Acetonitrile and 0.01 N sodium hydroxide (50:50)

Mobile phase: Acetonitrile and Buffer (35:65)

Acid stage standard solution: 0.22 mg/mL of USP Pantoprazole Sodium RS in Diluent

Acid stage sample solution: Nominally 0.2 mg/mL of pantoprazole prepared as follows. After 2 h in the Acid stage medium, drain and remove the Tablet from the basket and transfer to a suitable volumetric flask. Add 80% of the final volume of Diluent and swirl until the Tablet disintegrates completely. Sonicate for about 25 min, shaking the flask every few minutes. Dilute with Diluent to volume. Centrifuge an aliquot, then pass a portion of the supernatant through a suitable filter.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 290 nm

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

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: NLT 2 times the retention time of pantoprazole

System suitability

Sample: Acid stage standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Acid stage standard solution and Acid stage sample solution

Calculate the percentage of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) dissolved in the Acid stage:

Result = A - (r_U/r_S) x C_S x (M_r1/M_r2) x (1/L) x 100

A = percentage of pantoprazole as determined in the Assay

r_U = peak response of pantoprazole from the Acid stage sample solution

r_S = peak response of pantoprazole from the Acid stage standard solution

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

M_r1 = molecular weight of pantoprazole, 383.37

M_r2 = molecular weight of pantoprazole sodium, 405.35

L = label claim (mg/Tablet)

Tolerances: NMT 10% of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) is dissolved.

Buffer stage

Buffer stage medium: pH 6.8 phosphate buffer; 900 mL, degassed

Apparatus 1: 100 rpm

Time: 45 min

Buffer and Mobile phase: Prepare as directed in the Acid Stage.

Buffer stage standard solution: (L/900) mg/mL of USP Pantoprazole Sodium RS from the Acid stage standard solution in Buffer stage medium, where L is the label claim in mg/Tablet. Immediately mix 5 mL of the solution with 1 mL of 0.1 N sodium hydroxide.

Buffer stage sample solution: After 2 h in the Acid stage medium continue with Buffer stage medium as follows. Completely drain the Acid stage medium carefully leaving the Tablet in the basket and add the Buffer stage medium. After 45 min, withdraw 10 mL of the solution under test, and pass it through a suitable filter of 0.45-µm pore size. Mix 5 mL of the test solution with 1 mL of 0.1 N sodium hydroxide.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 290 nm

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

Flow rate: 1.5 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention time of pantoprazole

System suitability

Sample: Buffer stage standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Buffer stage standard solution and Buffer stage sample solution

Calculate the percentage of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) dissolved:

Result = (r_U/r_S) x C_S x V x (M_r1/M_r2) x (1/L) x 100

r_U = peak response of pantoprazole from the Buffer stage sample solution

r_S = peak response of pantoprazole from the Buffer stage standard solution

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

V = volume of Buffer stage medium, 900 mL

M_r1 = molecular weight of pantoprazole, 383.37

M_r2 = molecular weight of pantoprazole sodium, 405.35

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of pantoprazole (C₁₆H₁₅F₂N₃O₄S) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Mobile phase, System suitability solution, Standard solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Diluted standard solution: 0.0004 mg/mL of USP Pantoprazole Sodium RS from Standard solution in 0.02 N sodium hydroxide

Sensitivity solution: 0.2 µg/mL of USP Pantoprazole Sodium RS from Diluted standard solution in 0.02 N sodium hydroxide

System suitability

Samples: System suitability solution, Diluted standard solution, and Sensitivity solution

[NOTE-See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 3 between pantoprazole and pantoprazole related compound A, System suitability solution

Tailing factor: NMT 2.0 for pantoprazole, System suitability solution

Relative standard deviation: NMT 10.0%, Diluted standard solution

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

Analysis

Samples: Diluted standard solution and Sample solution

Calculate the percentage of any impurity in the portion of Tablets taken:

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

r_U = peak response of any impurity from the Sample solution

r_S = peak response of pantoprazole from the Diluted standard solution

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

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

M_r1 = molecular weight of pantoprazole, 383.37

M_r2 = molecular weight of pantoprazole sodium, 405.35

Acceptance criteria: See Table 2. The reporting threshold is 0.1%.

Table 2

^a 5-Difluoromethoxy-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1-methyl-1H-benzimidazole.

^b 6-Difluoromethoxy-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1-methyl-1H-benzimidazole.

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

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed containers. Store at controlled room temperature.

6.2 LABELING

Label Tablets to indicate that they must not be split, chewed, or crushed before administration. When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.

6.3 USP REFERENCE STANDARDS (11)

USP Pantoprazole Sodium RS

USP Pantoprazole Related Compound A RS

5-(Difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfonyl]-1H-benzimidazole.

C₁₆H₁₅F₂N₃O₅S 399.37

USP Pantoprazole Related Compound B RS

5-(Difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylthio]-1H-benzimidazole.

C₁₆H₁₅F₂N₃O₃S 367.37