Pantoprazole-Sodium-中国药典标准翻译.doc

Pantoprazole Sodium C16H14F2N3NaO4S·H2O 423.378 Pantoprazole Sodium is 5-difluoromethoxy-2-[[(3,4-dimethoxy-2-pyridinyl)methyl] sulfinyl]-1H-benzimidazole sodium, monohydrate. It contains not less than 98.0% and not more than 102.0% of C16H14F2N3NaO4S, calculated on anhydrous basis. [Description] A white or almost white crystalline powder. Freely soluble in water or methanol; practically insoluble in chloroform or diethyl ether. [Identification] (1) Dissolve 10 mg in 20 ml of water to 2 ml of the resulting solution add 5 drops of dilute hydrochloric acid, then add 1 ml of silicotungstic acid TS dropwise, a white curdy precipitate is produced. (2) The light absorption of a solution of 15 μg per ml in ethanol exhibits a maximum at 292 nm, and minimum at 250 nm (Appendix Ⅳ A). (3) The infrared absorption spectrum is concordant with the reference spectrum of pantoprazole sodium (Appendix ⅩⅥ). (4) Yields the reaction characteristic of sodium salts (Appendix Ⅲ). [Inspection] Alkalinity An aqueous solution of 20 mg per ml, pH 9.5-11.0 (Appendix Ⅵ H). Clarity and colour of solution Dissolve 0.20 g in 10 ml of water, the solution is clear and colourless; any colour produced is not more intense than that of reference solution Y2 (Appendix Ⅸ A, method 1). Related substances Dissolve a quantity of the product in solvent [0.001 mol/L sodium hydroxide-acetonitrile (1:1)] to obtain a solution of 0.4 mg per ml as test solution. Pipet accurately 1 ml of the test solution, to a 100 ml volumetric flask, dilute to volume with above solvent, mix well as reference solution. Carry out the method for high performance liquid chromatogrphy (Appendix Ⅴ D). The column is packed with octadecyl silane bonded silica gel, mobile phase A is 0.01 mol/L dipotassium hydrogen phosphate solution (adjust the pH to 7.0 by phosphoric acid), mobile phase B is acetonitrile, gradient elution chromatography is applied as the table below; detection wavelength is 289 nm; column temperature is 40℃. The number of the theoretical plates calculated from pantoprazole peak is not less than 2500. Inject 20 μl of reference solution, adjust detection sensitivity so that the peak height of the principle peak in the chromatogram is about 20% of full scale of the chart. Inject separately 20 μl of the test solution and the reference solution and record the chromatogram. The area of individual impurity peak is not more than 0.3 times of the area (0.3%) of the principle peak in the chromatogram obtained with the reference solution., the sum of the areas of the impurity peaks is not more than 0.8 of the area (for injection) (0.8%) or not more than the area (for oral) (1.0%) of the principle peak in the chromatogram obtained with the reference solution. The area of any peak in the chromatogram of the test solution less than 0.05 times of principle peak area obtained with the reference solution is negligible. Time(min) Flowing phase A (%) Flowing phase B (%) 0 90 10 30 60 40 45 15 85 Residual solvents toluene and acetone Transfer 0.2 g of the product, accurately weighted, to a headspace vial, dissolve with 2 ml of water and seal it up as test solution. Measure accurately a properquantity of tuluene and acetone, diluted quantitatively with water to obtain a mixed solution contain about 90 μg of toluene and 500 μg of acetone per ml(toluene is insoluble in water, dissolve it in DMF first and then disperse in the solvent), measure accurately 2ml of it into a headspace vial, and seal it up as reference solution. Carry out the method for Appendix Ⅷ P, method 2. The column is packed with 5% phenyl-95% polydimenthyl siloxane (or with similar polarity). Temperature program: initial temperature 40℃ for 4 minutes, then raise the temperature at a rate of 20℃ per min to 150℃ and hold for 3 minutes, the inlet temperature is 200℃, the detector temperature is 250℃; the head vial equilibration temperature is 60℃, equilibration time is 30 minutes. Inject separately the test preparation and the reference preparation and record the chromatogram. Calculate the quantity by peak area using external standard method, the content of tuluene and acetone shall meet the specification. Water According to method of moisture test (Appendix Ⅷ M Method One), the moisture should be 4.0%~6.0%. Heavy metals Transfer 0.5g of the product to a platinum crucible, then slowly Ignite the crucible until the product is the completely carbonized (about4 hours), cool the crucible in a desiccators, Moisten the sample with a small amount (usually 1.2~1.5mL) of sulfuric acid, then heat gently at a temperature as low as practicable until the steam of sulfuric acid is wiped off, add 0.5ml of nitric acid, keep heating until the fumes are no longer evolved, then ignite at 500~600℃ until the residue is completely incinerated, cool the crucible. The test is carried out according to Appendix Ⅷ H Method Two, starts from “add 2ml of hydrochloric acid”. The heavy metals s