Action and use
Histamine H2 receptor antagonist; treatment of peptic ulcer disease.
DEFINITION
Ranitidine Oral Solution is a solution of Ranitidine Hydrochloride in a suitable vehicle.
The oral solution complies with the requirements stated under Oral Liquids and with the following requirements.
Content of ranitidine, C13H22N4O3S
90.0 to 105.0% of the stated amount.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Prepare a solid phase extraction cartridge containing a C18 sorbent (Sep-Pak C18 cartridges are suitable) by passing 10 mL of methanol followed by 20 mL of 0.5M ammonia through the cartridge; attach the tip of a suitable syringe to the cartridge. Transfer a quantity of the oral solution containing the equivalent of 10 mg of ranitidine to the barrel of the syringe, add 2 mL of 0.5M ammonia to the syringe, insert the plunger and slowly force the mixture through the cartridge, discarding the eluant; repeat with two 4-mL quantities of 0.5M ammonia discarding the eluant. Pass two 5-mL quantities of a mixture of 25 volumes of 0.1M hydrochloric acid and 75 volumes of methanol through the cartridge and collect the eluant;
add 40 mL of absolute ethanol to the collected eluant, evaporate the resulting solution to dryness at a temperature not exceeding 30° under reduced pressure and dissolve the residue in 1 mL of methanol.
(2) Prepare in the same manner as solution (1) using a solution containing 1.12% w/v of ranitidine hydrochloride BPCRS in water in place of the preparation being examined.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel (Merck silica gel 60 plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 2 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air and expose to iodine vapour in a closed chamber until the spots are visible.
MOBILE PHASE
4 volumes of water, 8 volumes of 18M ammonia, 30 volumes of propan-2-ol and 50 volumes of ethyl acetate.
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).
B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is the same as that of the principal peak in the chromatogram obtained with solution (2).
TESTS
Acidity or alkalinity
pH, 6.7 to 7.5, Appendix V L.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Prepare a solid phase extraction cartridge containing a C18 sorbent (Sep-Pak C18 cartridges are suitable) by passing 10 mL of methanol followed by 20 mL of 0.5M ammonia through the cartridge; attach the tip of a suitable syringe to the cartridge. Transfer a weighed quantity of the oral solution containing the equivalent of 15 mg of ranitidine to the barrel of the syringe, add 2 mL of 0.5M ammonia to the syringe, insert the plunger and slowly force the mixture through the cartridge, discarding the eluant; repeat with two 4 mL quantities of 0.5M ammonia discarding the eluant. Pass two 5-mL quantities of a mixture of 25 volumes of 0.1M hydrochloric acid and 75 volumes of methanol through the cartridge and collect the eluant; add 40 mL of absolute ethanol to the collected eluant, evaporate the resulting solution to dryness at a temperature not exceeding 30° under reduced pressure and dissolve the residue in 2 mL of water.
(2) Dilute 1 volume of solution (1) to 50 volumes with water.
(3) Dilute 1 volume of solution (1) to 100 volumes with water.
(4) Dilute 1 volume of solution (1) to 200 volumes with water.
(5) Dilute 1 volume of solution (3) to 5 volumes with water.
(6) Dissolve the contents of a vial of ranitidine impurity J EPCRS in 1 mL of a solution containing 0.15% w/v of ranitidine hydrochloride BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (10 cm × 4.6 mm) packed with octadecylsilyl amorphous organosilica polymer (3.5 μm) (XTerra MS C18 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use a column temperature of 35°.
(e) Use a detection wavelength of 230 nm.
(f) Use an injection volume of 20 μL for each solution.
MOBILE PHASE
Buffer solution Adjust the pH of 950 mL of 0.05M potassium dihydrogen orthophosphate to 7.1 by adding strong sodium hydroxide solution and dilute to 1 litre.
Mobile phase A: 2 volumes of acetonitrile and 98 volumes of buffer solution.
Mobile phase B: 22 volumes of acetonitrile and 78 volumes of buffer solution.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0-10 | 100→0 | 0→100 | linear gradient |
| 10-15 | 0 | 100 | isocratic |
| 15-16 | 0→100 | 100→0 | linear gradient |
| 16-20 | 100 | 0 | re-equilibration |
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (6), the resolution between the two principal peaks is at least 1.5.
LIMITS
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (2%);
the area of not more than one secondary peak is greater than the area of the principal peak in the chromatogram obtained with solution (3) (1%);
the area of not more than two other secondary peaks is greater than the area of the principal peak in the chromatogram obtained with solution (4) (0.5%);
the area of not more than two further secondary peaks is greater than the principal peak in solution (5) (0.2%);
the sum of the areas of all secondary peaks is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (5%).
Disregard any peak with an area less than 0.25 times the area of the principal peak in the chromatogram obtained with solution (5) (0.05%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dilute a weighed quantity of the oral solution containing the equivalent of 10 mg of ranitidine with sufficient of the mobile phase to produce 100 mL.
(2) 0.0112% w/v of ranitidine hydrochloride BPCRS in the mobile phase.
(3) 0.0112% w/v of ranitidine hydrochloride BPCRS and 0.0002% w/v of dimethyl{5-[2-(1-methylamino-2-nitrovinylamino)ethylsulfinylmethyl]furfuryl}amine BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) A stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (10 μm) (Partisil ODS 1 is suitable).
(b) Isocratic elution using the mobile phase described below.
(c) Flow rate of 2 mL per minute.
(d) Ambient column temperature.
(e) Detection wavelength of 322 nm.
(f) Injection volume of 20 μL for each solution.
MOBILE PHASE
15 volumes of 0.1M ammonium acetate and 85 volumes of methanol.
SYSTEM SUITABILITY
The assay is not valid unless the peak due to ranitidine in the chromatogram obtained with solution (3) shows baseline separation from the peak due to dimethyl{5-[2-(1-methylamino-2-nitrovinylamino)ethylsulfinylmethyl]furfuryl}amine.
DETERMINATION OF CONTENT
Determine the weight per mL of the oral solution, Appendix V G, and calculate the content of C13H22N4O3S, weight in volume, using the declared content of C13H22N4O3S in ranitidine hydrochloride BPCRS.
STORAGE
Ranitidine Oral Solution should be protected from light.
LABELLING
The quantity of active ingredient is stated in terms of the equivalent amount of ranitidine.
