Monographs: Pharmaceutical substances: Amikacinum - Amikacin

Molecular formula. C₂₂H₄₃N₅O₁₃

Relative molecular mass. 585.6

Graphic formula.

Chemical name. O-3-Amino-3-deoxy-α-D-glucopyranosyl-(1→4)-O-[6-amino-6-deoxy-α-D-glucopyranosyl-(1→6)]-N³-(4-amino-L-2-hydroxybutyryl)-2-deoxy-L-streptamine; (S)-O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→6)-O-[6-amino-6-deoxy-α-D-glucopyranosyl-(1→4)]-N¹-(4-amino-2-hydroxyoxobutyl)-2-deoxy-D-streptamine; CAS Reg. No. 37517-28-5.

Description. A white, crystalline powder; almost odourless.

Solubility. Sparingly soluble in water.

Category. Antibacterial drug.

Storage. Amikacin should be kept in a tightly closed container.

Requirements

Definition. Amikacin contains not less than 900 μg of C₂₂H₄₃N₅O₁₃ per mg, with reference to the anhydrous substance.

Identity tests

A. Dissolve 10 mg in 1 ml of water, add 1 ml of sodium hydroxide (~80 g/l) TS and mix, then add 2 ml of cobalt(II) nitrate (10 g/l) TS; a violet colour is produced.

B. Dissolve 0.05 g in 3 ml of water and add 4 ml of anthrone TS; a bluish violet colour is produced.

Specific optical rotation. Use a 20 mg/ml solution and calculate with reference to the anhydrous substance: .

Sulfated ash. After ignition moisten the residue with 2 ml of nitric acid (~1000 g/l) TS and about 0.2 ml of sulfuric acid (~1760 g/l) TS; not more than 10 mg/g.

Water. Determine as described under 2.8 Determination of water by the Karl Fischer method, Method A, using about 0.2 g of the substance; the water content is not more than 85 mg/g.

pH value. pH of a 10 mg/ml solution in carbon-dioxide-free water R, 9.5-11.5.

Assay. Carry out the assay as described under 3.1 Microbiological assay of antibiotics, using either (a) Bacillus subtilis (ATCC 6633) as the test organism, culture medium Cm1 with a final pH of 6.5-6.7, sterile phosphate buffer pH 6.0 TS1, TS2 or TS3, an appropriate concentration of amikacin (usually 5-20 μg/ml), and an incubation temperature of 32-35 °C, or (b) Staphylococcus aureus (ATCC 29737) as the test organism, the same culture medium and phosphate buffer, an appropriate concentration of amikacin (usually 10 μg/ml), and the same incubation temperature. The precision of the assay is such that the fiducial limits of error of the estimated potency (P = 0.95) are not less than 95% and not more than 105% of the estimated potency. The upper fiducial limit of error of the estimated potency (P = 0.95) is not less than 900 μg per mg, calculated with reference to the anhydrous substance.