Action and use
Histamine H2 receptor antagonist; treatment of peptic ulcer disease.
DEFINITION
Ranitidine Injection is a sterile solution of Ranitidine Hydrochloride in Water for Injections.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of ranitidine, C13H22N4O3S
92.5 to 105.0% of the stated amount.
IDENTIFICATION
A. To a volume of the injection containing the equivalent of 25 mg of ranitidine add 20 mL of methanol, mix and evaporate to dryness. Add 1 mL of petroleum spirit (boiling range, 60° to 80°) to the resulting residue, scratch the side of the vessel with a glass rod to induce crystallisation, evaporate to dryness and dry the residue at 60° for 10 minutes. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of ranitidine
hydrochloride (RS 311).
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
Buffered formulations, pH 6.7 to 7.3; unbuffered formulations, pH 4.5 to 7.0, Appendix V L.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dilute, if necessary, a volume of the injection with water to contain the equivalent of 0.1% w/v of ranitidine.
(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 solution (1).
CHROMATOGRAPHIC CONDITIONS
(a) A stainless steel column (10 cm × 4.6 mm) packed with octadecylsilyl amorphous organosilica polymer (3.5 μm) (Waters XTerra MS C18 is suitable).
(b) Gradient elution using the mobile phase described below.
(c) Flow rate of 1.5 mL per minute.
(d) Column temperature of 35°.
(e) Detection wavelength of 230 nm.
(f) 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.
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%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dilute a volume of the injection with sufficient of the mobile phase to contain the equivalent of 0.01% w/v of ranitidine.
(2) 0.0112% w/v of ranitidine hydrochloride BPCRS in 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 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
Calculate the content of C13H22N4O3S in the injection using the declared content of C13H22N4O3S in ranitidine hydrochloride BPCRS.
STORAGE
Ranitidine Injection should be protected from light.
LABELLING
The label states (1) the quantity of active ingredient in terms of the equivalent amount of ranitidine; (2) where appropriate, that the injection is buffered.
