Amikacin Sulfate

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₂₂H₄₃N₅O₁₃ · xH₂SO₄

D-Streptamine, 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-, (S)-, sulfate (1:2 or 1:1.8 salt);

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-d-streptamine sulfate (1:2 or 1:1.8 salt);

(2S)-4-Amino-N-{(1R,2S,3S,4R,5S)-5-amino-2-[(3-amino-3-deoxy-α-d-glucopyranosyl)oxy]-4-[(6-amino-6-deoxy-α-d-glucopyranosyl)oxy]-3-hydroxycyclohexyl}-2-hydroxybutanamide sulfate (1:2 or 1:1.8 salt).

C₂₂H₄₃N₅O₁₃ · 1.8H₂SO₄ 762.15 CAS RN®: 149022-22-0.

C₂₂H₄₃N₅O₁₃ · 2H₂SO₄ 781.76 CAS RN®: 39831-55-5; UNII: N6M33094FD.

1 DEFINITION

Amikacin Sulfate having a molar ratio of amikacin to sulfuric acid (H₂SO₄) of 1:2 contains the equivalent of NLT 674 μg/mg and NMT 786 μg/mg of amikacin (C₂₂H₄₃N₅O₁₃), calculated on the dried basis. Amikacin Sulfate having a molar ratio of amikacin to sulfuric acid (H₂SO₄) of 1:1.8 contains the equivalent of NLT 691 μg/mg and NMT 806 μg/mg of amikacin (C₂₂H₄₃N₅O₁₃), calculated on the dried basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K or 197A

Acceptance criteria: The IR absorption spectrum conforms to that of USP Amikacin Sulfate RS, similarly obtained.

B. The retention time of the peak for amikacin of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

C. Identification Tests-General 〈191〉, Chemical Identification Tests, Sulfate: Meets the requirements

3 ASSAY

Change to read:

3.1 Procedure

Mobile phase: 134 mM sodium hydroxide, prepared as follows. Transfer a volume of deionized water to a suitable plastic container, sonicate, degas, and sparge with helium. While stirring, slowly add sodium hydroxide solution of a suitable concentration.

[Note-Prepare fresh daily. The Mobile phase readily absorbs carbon dioxide and produces carbonate that changes the retention time of amikacin. The use of a 50% (w/w), low-carbonate sodium hydroxide solution is recommended.]

System suitability solution: 0.02 mg/mL of USP Amikacin RS and 0.008 mg/mL of USP Kanamycin Sulfate RS in water

Standard solution: 0.02 mg/mL of USP Amikacin RS in water

Sample solution: Equivalent to 0.02 mg/mL of amikacin, from Amikacin Sulfate, in water

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Electrochemical

Mode: Integrated amperometric

Electrodes

Working: Gold

Reference: Silver-silver chloride

Detector settings: See Table 1.

Table 1

Column: 4-mm × 25-cm; 7.5-μm packing L47

[Note-A guard column of packing L47 is recommended.]

Flow rate: 0.5 mL/min

Injection volume: 20 μL

3.3 System suitability

Samples: System suitability solution and Standard solution

[Note-The relative retention times for kanamycin and amikacin are 0.8 and 1.0, respectively.]

3.4 Suitability requirements

Resolution: NLT 3 between kanamycin and amikacin, System suitability solution

Tailing factor: NMT 2, Standard solution

Relative standard deviation: NMT 3%, Standard solution

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the quantity, in μg, of amikacin (C₂₂H₄₃N₅O₁₃) in each mg of Amikacin Sulfate taken:

Result = (r_u/r_s) × (C_s/C_u) × P × F

r_u = peak response of amikacin from the Sample solution

r_s = peak response of amikacin from the Standard solution

C_s = concentration of USP Amikacin RS in the Standard solution (mg/mL)

C_u = concentration of Amikacin Sulfate (ERR 1-Dec-2023) in the Sample solution (mg/mL)

P = potency of amikacin in USP Amikacin RS (mg/mg)

F = conversion factor, 1000 μg/mg

Acceptance criteria: See Table 2.

Table 2

^a Calculated on the dried basis.

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 1.0%, the charred residue being moistened with 2 mL of nitric acid and 5 drops of sulfuric acid

5 SPECIFIC TESTS

Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 20 mg/mL in water

Acceptance criteria: +76° to +84°

Crystallinity 〈695〉: Meets the requirements

pH 〈791〉

Sample solution: 10 mg/mL in water

Acceptance criteria: See Table 3.

Table 3

Loss on Drying 〈731〉

Sample: 100 mg

Analysis: Dry the Sample under vacuum at a pressure not exceeding 5 mm of mercury at 110° for 3 h.

Acceptance criteria: NMT 13.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

Labeling: Label it to indicate whether its molar ratio of amikacin to sulfuric acid (H₂SO₄) is 1:2 or 1:1.8.

USP Reference Standards 〈11〉

USP Amikacin RS

USP Amikacin Sulfate RS

USP Kanamycin Sulfate RS