Edition: BP 2025 (Ph. Eur. 11.6 update)
DEFINITION
Mannitol Infusion is a sterile solution containing Mannitol. It is supplied as a ready-to-use solution.
The infusion complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of mannitol, C6H14O6
95.0 to 105.0% of the stated amount.
CHARACTERISTICS
A colourless or almost colourless solution.
IDENTIFICATION
A. Evaporate to dryness on a water bath a volume containing 0.2 g of Mannitol. The melting point of the residue, Appendix V A, is about 167°.
B. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Dilute a volume of the infusion with water to contain 0.25% w/v of Mannitol.
(2) 0.25% w/v of mannitol EPCRS in water.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel G.
(b) Use the mobile phase as described below.
(c) Apply 2 µL of each solution.
(d) Develop the plate to 17 cm.
(e) After removal of the plate, dry in air and spray with a 0.2% w/v solution of sodium periodate. Allow the plate to dry in air for 15 minutes and spray with a 2% w/v solution of 4,4′-methylenebis-N,N-dimethylaniline in a mixture of 1 volume of glacial acetic acid and 4 volumes of acetone.
MOBILE PHASE
10 volumes of water, 20 volumes of ethyl acetate and 70 volumes of propan-1-ol.
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) is similar in position, colour and size to that in the chromatogram obtained with solution (2).
C. Add 0.3 mL of a solution containing 10% w/v of Mannitol to 3 mL of a cooled mixture prepared by adding 6 mL of sulfuric acid to 3 mL of a freshly prepared 10% w/v solution of catechol while cooling in ice. Heat gently over a naked flame for about 30 seconds. A pink colour develops.
TESTS
Acidity or alkalinity
pH, 4.5 to 7.0, Appendix V L, when determined on solutions diluted, if necessary, with water for injections to contain 10% w/v of Mannitol and to which 0.30 mL of a saturated solution of potassium chloride has been added for each 100 mL of solution.
Reducing sugars
Add 20 mL of cupri-citric solution and a few glass beads to a volume of the infusion containing 5 g of Mannitol. Heat so that boiling begins after 4 minutes and continue boiling for 3 minutes. Cool rapidly and add 100 mL of a 2.4% v/v solution of glacial acetic acid and 20 mL of 0.025M iodine VS. With continuous shaking add 25 mL of a mixture of 6 volumes of hydrochloric acid and 94 volumes of water and, when the precipitate has dissolved, titrate the excess of iodine with 0.05M sodium thiosulfate VS using 1 mL of starch solution, added towards the end of the titration, as indicator. Not less than 12.8 mL of 0.05M sodium thiosulfate VS is required.
Bacterial endotoxins
The endotoxin limit concentration is 0.5 IU per mL, Appendix XIV C. Dilute infusions containing more than 10% w/v (100 g/L) of Mannitol with water BET to contain 10% w/v.
ASSAY
Dilute a quantity containing 0.4 g of Mannitol to 100 mL with water, transfer 10 mL to a stoppered flask, add 20 mL of 0.1M sodium periodate and 2 mL of 1M sulfuric acid and heat on a water bath for 15 minutes. Cool, add 3 g of sodium hydrogen carbonate and 25 mL of 0.1M sodium arsenite VS, mix, add 5 mL of a 20% w/v solution of potassium iodide, allow to stand for 15 minutes and titrate with 0.05M iodine VS until the first trace of yellow colour appears. Repeat the operation without the substance being examined. The difference between the titrations represents the amount of iodine required. Each mL of 0.05M iodine VS is equivalent to 1.822 mg of C6H14O6.
STORAGE
Mannitol Infusion should be stored at a temperature of 20° to 30°. Exposure to lower temperatures may cause the deposition of crystals, which should be dissolved by warming before use.
