Monographs: Pharmaceutical substances: Amikacini sulfas - Amikacin sulfate

Amikacin sulfate (non-injectable)

Amikacin sulfate, sterile

Molecular formula. C₂₂H₄₃N₅O₁₃,2H₂SO₄

Relative molecular mass. 781.8

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 sulfate (1:2) (salt); (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-hydroxy-1-oxobutyl)-2-deoxy-D-streptamine sulfate (1:2) (salt); CAS Reg. No. 39831-55-5.

Description. A white to yellowish white, crystalline powder; almost odourless.

Solubility. Very soluble in water; practically insoluble in methanol R, acetone R or ether R.

Category. Antibacterial drug.

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

Labelling. The designation sterile Amikacin sulfate indicates that the substance complies with the additional requirements for sterile Amikacin sulfate and may be used for parenteral administration or for other sterile applications.

Requirements

Definition. Amikacin sulfate contains not less than 650 International Units 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.

C. A 20 mg/ml solution yields reaction A described under 2.1 General identification tests as characteristic of sulfates.

Specific optical rotation. Use a 10 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 50 mg/g.

pH value. pH of a 10 mg/ml solution in carbon-dioxide-free water R, 6.0-7.5.

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 IU per 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 IU per 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 650 IU per mg, calculated with reference to the anhydrous substance.

Additional Requirements for Amikacin Sulfate for sterile use

Storage. Sterile Amikacin sulfate should be kept in a hermetically closed container.

Sterility. Complies with 3.2.2 Sterility testing of antibiotics, applying the membrane filtration test procedure and using the sampling plan described under 3.2.1 Test for sterility of non-injectable preparations

Additional requirements for Amikacin sulfate for parenteral use

Complies with the monograph for "Parenteral preparations".

Bacterial endotoxins. Carry out the test as described under 3.4 Test for bacterial endotoxins; contains not more than 0.33 IU of endotoxin RS per mg of amikacin.