Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Organic base used in the preparation of organic acids.
DEFINITION
Meglumine Amidotrizoate Injection is a sterile solution of the Meglumine salt of Amidotrizoic Acid Dihydrate in Water for Injections.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of meglumine amidotrizoate, C11H9I3N2O4,C7H17NO5
97.0 to 103.0% of the stated amount.
CHARACTERISTICS
A colourless to pale yellow, slightly viscous liquid.
IDENTIFICATION
A. Evaporate 2 mL of the injection to dryness and heat 50 mg of the residue. Violet vapours of iodine are evolved.
B. To 20 mg of the residue obtained by evaporating the injection to dryness add 5 mL of 1M sodium hydroxide and boil gently under a reflux condenser for 10 minutes. Cool, add 5 mL of 2M hydrochloric acid and cool in ice for 5 minutes. Add 4 mL of a 1% w/v solution of sodium nitrite, cool in ice for 5 minutes, add 0.3 g of sulfamic acid, swirl gently until effervescence ceases and add 2 mL of a 0.4% w/v solution of N-(1-naphthyl)ethylenediamine dihydrochloride. An orange- red colour is produced.
C. To a quantity containing 1 g of meglumine amidotrizoate add 50 mL of water and a slight excess of 2M hydrochloric acid and filter. Evaporate the filtrate to dryness on a water bath, dissolve the residue in a small quantity of boiling ethanol (90%), filter and cool the filtrate in ice. The melting point of the dried precipitate is about 146°, Appendix V A.
TESTS
Acidity or alkalinity
pH, 6.0 to 7.0, Appendix V L.
Meglumine
22.9 to 25.3% of the stated content of meglumine amidotrizoate when determined by the following method. Measure the optical rotation of the injection, Appendix V F, using a 2-dm tube. Calculate the percentage content of meglumine using the expression 2.104R where R is the numerical value of the rotation.
Free amine
To a quantity containing 1 g of meglumine amidotrizoate in a 50 mL glass-stoppered graduated flask add sufficient water to produce 5 mL, 10 mL of 0.1M sodium hydroxide and 25 mL of dimethyl sulfoxide. Stopper the flask, mix the contents by gentle swirling and cool in ice, protected from light. After 5 minutes add slowly 2 mL of hydrochloric acid, mix and allow to stand for 5 minutes. Add 2 mL of a 2% w/v solution of sodium nitrite, mix and allow to stand for 5 minutes. Add 1 mL of an 8% w/v solution of sulfamic acid, mix and allow to stand for 5 minutes. Add 2 mL of a 0.1% w/v solution of N-(1- naphthyl)ethylenediamine dihydrochloride in a 70% v/v solution of propane-1,2-diol and mix. Remove the flask from the ice and allow to stand in water at 22° to 25° for 10 minutes, occasionally shaking gently. Add sufficient dimethyl sulfoxide to produce 50 mL and mix. Within 5 minutes of diluting to 50 mL measure the absorbance of the resulting solution at the maximum at 470 nm, Appendix II B, using in the reference cell a solution prepared by treating 5 mL of water in the same manner. The absorbance is not more than 0.40.
Inorganic iodide
Dilute a quantity containing 0.80 g of meglumine amidotrizoate to 10 mL with water, add sufficient 2M nitric acid dropwise to ensure complete precipitation of the iodinated acid and add 3 mL in excess. Filter, wash the precipitate with 5 mL of water, add to the filtrate 1 mL of hydrogen peroxide solution (100 vol) and 1 mL of chloroform and shake. Any purple colour in the chloroform layer is not more intense than that obtained by adding 2 mL of iodide standard solution (20 ppm I) to a mixture of 3 mL of 2M nitric acid and sufficient water to equal the volume of the test solution, adding 1 mL of hydrogen peroxide solution (100 vol) and 1 mL of chloroform and shaking (50 ppm).
Bacterial endotoxins
Carry out the test for bacterial endotoxins, Appendix XIV C. The endotoxin limit concentration is less than 1.0 IU per mL of Meglumine Amidotrizoate Injection.
ASSAY
Mix a quantity containing 0.5 g of meglumine amidotrizoate with 12 mL of 5M sodium hydroxide and 20 mL of water, add 1 g of zinc powder and boil under a reflux condenser for 30 minutes. Cool, rinse the condenser with 30 mL of water, filter through absorbent cotton and wash the flask and filter with two 20 mL quantities of water. To the combined filtrate and washings add 80 mL of hydrochloric acid, cool and titrate with 0.05M potassium iodate VS until the dark brown solution becomes light brown. Add 5 mL of chloroform and continue the titration, shaking well after each addition, until the chloroform becomes colourless. Each mL of 0.05M potassium iodate VS is equivalent to 26.97 mg of C11H9I3N2O4,C7H17NO5. Determine the weight per mL of the injection, Appendix V G, and calculate the percentage w/v of C11H9I3N2O4,C7H17NO5.
STORAGE
Meglumine Amidotrizoate Injection should be protected from light.
LABELLING
The strength is stated as the percentage w/v of meglumine amidotrizoate.
