Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Proton pump inhibitor; treatment of peptic ulcer disease.
DEFINITION
Pantoprazole for Injection is a sterile material consisting of Pantoprazole Sodium Sesquihydrate with or without excipients. It is supplied in a sealed container.
The contents of the sealed container comply with the requirements for Powders for Injections or Infusions stated under Parenteral Preparations and with the following requirements.
Content of pantoprazole, C16H15F2N3O4S
93.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the powder containing the equivalent of 40 mg of pantoprazole with 10 mL of acetone, filter (Whatman GF/C is suitable) and evaporate to dryness. Dry the residue at 60° for 30 minutes. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of pantoprazole sodium (RS 488).
TESTS
Alkalinity
pH of a solution containing the equivalent of 0.4% w/v of pantoprazole, 9.0 to 11.5, Appendix V L.
Clarity and colour of solution
A solution containing the equivalent of 0.4% w/v of pantoprazole is clear, Appendix IV A, and not more intensely coloured than reference solution B5 or BY5, Appendix IV B, Method II.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
Prepare a solution containing equal volumes of acetonitrile and 0.001M sodium hydroxide (solution A).
(1) Shake a quantity of the powder for injection containing the equivalent of 40 mg of pantoprazole in 50 mL of solution A, dilute with sufficient solution A to produce 100 mL and filter.
(2) Dilute 1 volume of solution (1) to 20 volumes. Dilute 1 volume of this solution to 10 volumes.
(3) 0.05% w/v of pantoprazole for system suitability EPCRS in solution A.
(4) Dilute 1 volume of solution (2) to 5 volumes.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (12.5 cm × 4 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Hypersil ODS is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use a column temperature of 40°.
(e) Use an autosampler temperature of 5°.
(f) Use a detection wavelength of 290 nm.
(g) Inject 20 µL of each solution.
MOBILE PHASE
Mobile phase A 0.01M dipotassium hydrogen phosphate trihydrate, adjusted to pH 7.0 with a 20% v/v solution of orthophosphoric acid.
Mobile phase B 1 volume of water and 99 volumes of acetonitrile.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0-3 | 90 | 10 | isocratic |
| 3-3390 | 90→60 | 10→40 | linear gradient |
| 33-48 | 60→15 | 40→85 | linear gradient |
| 48-50 | 15→90 | 85→10 | linear gradient |
| 50-60 | 90 | 10 | re-equilibration |
When the chromatograms are recorded under the prescribed conditions the retention times relative to pantoprazole (retention time about 22 minutes) are: impurity C, about 0.6; impurity A, about 0.9; impurity D + F, about 1.1; impurity E, about 1.3 and impurity B, about 1.4.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity D + F and pantoprazole is greater than 3.0.
LIMITS
Identify any peak in the chromatogram obtained with solution (1) due to impurity C using the chromatogram obtained with solution (3) and multiply the area of this peak by a correction factor of 0.6.
In the chromatogram obtained with solution (1):
the area of any peak due to impurities D + F (combined peak area) is not greater than 3 times the area of the principal peak in the chromatogram obtained with solution (2) (1.5%);
the area of any peak due to impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5% of each);
the area of any other secondary peak is not greater than 0.4 times the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any secondary peaks is not greater than 4 times the area of the principal peak in the chromatogram obtained with solution (2) (2.0%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.1%).
ASSAY
Determine the weight of the contents of 10 containers as described in the test for uniformity of weight, Appendix XII C1, Powders for Parenteral Use.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
Prepare a solution containing equal volumes of acetonitrile and 0.001M sodium hydroxide (solution A).
(1) Prepare 10 injections following the manufacturer’s instructions and combine the resulting solutions. Dilute a quantity of the resulting solution with sufficient solution A to produce a solution containing the equivalent of 0.004% w/v of pantoprazole.
(2) 0.0045% w/v of pantoprazole sodium BPCRS in solution A.
(3) 0.0045% w/v of pantoprazole sodium BPCRS and 0.0005% w/v of pantoprazole impurity A BPCRS in solution A.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (12.5 cm × 4 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Hypersil ODS is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use an autosampler temperature of 5°.
(f) Use a detection wavelength of 290 nm.
(g) Inject 20 µL of each solution.
MOBILE PHASE
35 volumes of acetonitrile, and 65 volumes of 0.01M dipotassium hydrogen phosphate trihydrate, previously adjusted to pH 7.0 with a 20% v/v solution of orthophosphoric acid.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity A and pantoprazole is at least 1.5.
DETERMINATION OF CONTENT
Calculate the content of C16H15F2N3O4S in the powder for injection from the chromatograms obtained and using the declared content of C16H15F2N3O4S in pantoprazole sodium BPCRS.
STORAGE
The sealed container should be protected from light and stored at a temperature not exceeding 25°.
LABELLING
The quantity of the active ingredient is stated in terms of the equivalent amount of pantoprazole.
IMPURITIES
The impurities limited by this monograph include those listed under Pantoprazole Sodium Sesquihydrate.
