Micafungin Sodium

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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C₅₆H₇₀N₉NaO₂₃S             1292.27

Pneumocandin A0, 1-[(4R,5R)-4,5-dihydroxy-N²-[4-[5-[4-(pentyloxy)phenyl]-3-isoxazolyl benzoyl]-l-ornithine)-4-[(4S)-4-hydroxy-4-(4-hydroxy-3-(sulfooxy)phenyl]-1-threonine]-, monosodium salt;

Sodium 5-[(1S,2S)-2-((2R,6S,9S,11R,12R,14aS,15S,16S,20S,23S,25aS)-20-[(R)-3-amino-1-hydroxy-3-oxopropyl]-2,11,12,15-tetrahydroxy-6-((R)-1-hydroxyethyl]-16-methyl-5,8,14,19,22,25-hexaoxo-9-(4-(5-[4-(pentyloxy)phenyl isoxazol-3-yl)benzamido)tetracosahydro-1H-dipyrrolo [2,1-c:2',1'-l][1,4,7,10,13,16] hexaazacyclohenicosin-23-yl)-1,2-dihydroxyethyl]-2-hydroxyphenyl sulfate   CAS RN^®: 208538-73-2.

UNII: IS1UP79R56

1 DEFINITION

Micafungin Sodium contains NLT 95.0% and NMT 102.0% of micafungin sodium (C₅₆H₇₀N₉NaO₂₃S ), calculated on the anhydrous and solvent- free basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A or 197K

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

C. IDENTIFICATION TESTS GENERAL (191), Chemical Identification Tests, Sodium: Meets the requirements

3 ASSAY

PROCEDURE

Conduct the entire procedure, without exposure to direct sunlight, using a light-resistant vessel.

Buffer: 18.7 g/L of sodium phosphate, monobasic, dihydrate and 7.7 g/L of sodium perchlorate in water. Adjust with 10% phosphoric acid to a pH of 3.0.

Mobile phase: Acetonitrile and Buffer (450:700)

Diluent: Acetonitrile and water (3:7)

Standard solution: 0.5 mg/mL of USP Micafungin Sodium RS in Diluent

Sample solution: 0.5 mg/mL of Micafungin Sodium in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Column temperature: 35°

Flow rate: 1 mL/min

Injection volume: 5 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of micafungin sodium (C₅₆H₇₀N₉NaO₂₃S) in the portion of Micafungin Sodium taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of micafungin from the Sample solution

r_S = peak response of micafungin from the Standard solution 

C_S = concentration of USP Micafungin Sodium RS in the Standard solution (mg/mL) 

C_U = concentration of Micafungin Sodium in the Sample solution (mg/mL)

Acceptance criteria: 95.0%-102.0% on the anhydrous and solvent-free basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

4.8%-5.8%

4.2 ORGANIC IMPURITIES

Conduct the entire procedure, without exposure to direct sunlight, using a light-resistant vessel.

Buffer and Mobile phase: Prepare as directed in the Assay.

Solution A: 35.8 g/L of sodium phosphate, dibasic, dodecahydrate

Solution B: 13.6 g/L of potassium phosphate, monobasic

Diluent: Solution A and Solution B (2:1); pH 7.0

System suitability solution: 4 mg/mL of USP Micafungin Sodium RS in Diluent

Sensitivity solution: 0.002 mg/mL of USP Micafungin Sodium RS in Diluent

Standard solution: 0.012 mg/mL of USP Micafungin Sodium RS in Diluent

Sample solution: 4 mg/mL of Micafungin Sodium in Diluent

Chromatographic system: Proceed as directed in the Assay, except for the Injection volume.

Injection volume: 2 µL

System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

[NOTE-See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.2 between micafungin and micafungin epimer, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Sample: Sample solution

Calculate the percentage of any individual impurity in the portion of Micafungin Sodium taken:

                         Result = (r_U/r_T)

r_U = peak response of any individual impurity

r_T = sum of all the peak responses

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.

Table 1

^a Sodium 5-[(1S,2S,3S)-4-(((2S,3R)-5-amino-1-[(2S,3S,4S)-2-carbamoyl-3-hydroxy-4-methylpyrrolidin-1-yl]-3-hydroxy-1,5-dioxopentan-2-yl)amino)-3-[(2S,4R)-1-([(2S,4R)-4,5-dihydroxy-1-(4-(5-[4-(pentyloxy)phenyl]isoxazol-3-yl)benzoyl)pyrrolidine-2-carbonyl]-L-threonyl)-4-hydroxypyrrolidine-2-carboxamido]-1,2-dihydroxy-4-oxobutyl]-2-hydroxyphenyl sulfate.

^b Sodium 5-[(1S,2S)-2-((2R,6S,9S,11R,12R, 14aS,15S,20S,23S,25aS)-20-[(R)-3-amino-1-hydroxy-3-oxopropyl]-2,11,12,15-tetrahydroxy-6-[(R)-1-,14,19,22,25-hexaoxo-9-(4-(5-[4-(pentyloxy)phenyl]isoxazol-3-yl)benzamido)tetracosahydro-1H-dipyrrolo[2,1-c:2,1'-[1,4,7,10,13,16] hexaazacyclohenicosin-23-yl)-1,2-dihydroxyethyl]-2-hydroxyphenyl sulfate.

^c Sodium 5-[(1S,2S)-2-((2R,6S,9S,11R,12R,14aS, 15S,16S,20S,23S,25aS)-20-[(R)-3-amino-1-hydroxy-3-oxopropyl]-2,11,12,15-tetrahydroxy-6-(hydroxymethyl)-16-methyl-5,8,14,19,22,25-hexaoxo-9-(4-(5-[4-(pentyloxy)phenyl isoxazol-3-yl)benzamido)tetracosahydro-1H-dipyrrolo[2,1-c:2',1'-1][1,4,7,10,13,16] hexaazacyclohenicosin-23-yl)-1,2-dihydroxyethyl]-2-hydroxyphenyl sulfate.

^d Sodium 5-[(1S,2S)-2-((2R,6S,95,11R,125,14aS, 15S, 16S,20S,23S,25aS)-20-((R)-3-amino-1-hydroxy-3-oxopropyl]-2,11,12,15-tetrahydroxy-6-[(R)-1-hydroxyethyl]-16-methyl-5,8,14,19,22,25-hexaoxo-9-(4-(5-[4-(pentyloxy)phenyl isoxazol-3-yl)benzamido)tetracosahydro-1H-dipyrrolo [2,1-c:2',1'-1][1,4,7,10,13,16] hexaazacyclohenicosin-23-yl)-1,2-dihydroxyethyl]-2-hydroxyphenyl sulfate.

^e Sodium 5-[(1S,2S)-2-((2R,6S,9S,12R, 14aS, 15S, 16S,205,23S,25aS)-20-((R)-3-amino-1-hydroxy-3-oxopropyl)-2,12,15-trihydroxy-6-((R)-1-hydroxyethyl]-16-methyl-5,8,14,19,22,25-hexaoxo-9-(4-(5-[4-(pentyloxy)phenyl]isoxazol-3-yl)benzamido)tetracosahydro-1H-dipyrrolo[2,1-c:2',1'-][1,4,7,10,13,16] hexaazacyclohenicosin-23-yl)-1,2-dihydroxyethyl]-2-hydroxyphenyl sulfate.

5 SPECIFIC TESTS

5.1 OPTICAL ROTATION (781S), Procedures. Specific Rotation

Sample solution: 20 mg/mL in water

Acceptance criteria: -20° to-22°, on the anhydrous and solvent-free basis, measured at 20°

5.2 MICROBIAL ENUMERATION TESTS (61) and TESTS FOR SPECIFIED MICROORGANISMS (62)

The total aerobic microbial count does not exceed 10³ cfu/g. The total molds and yeasts count does not exceed 10² cfu/g.

5.3 BACTERIAL ENDOTOXINS TEST (85)

Meets the requirements

5.4 WATER DETERMINATION (921), Method I, Method la

Sample: 0.5 g

Analysis: Use a mixture of formamide and methanol (2:1) as the solvent.

Acceptance criteria: NMT 8.0%

5.5 PH (791)

Sample: 100 mg/mL

Acceptance criteria: 5.0-7.2

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers. Store between 2° and 8°.

USP REFERENCE STANDARDS (11)

USP Micafungin Sodium RS_{▲(USP 1-Aug-2023)}