Micafungin for Injection

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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1 DEFINITION

Micafungin for Injection contains an amount of Micafungin Sodium equivalent to NLT 95% and NMT 115% of the labeled amount of micafungin (C₅₆H₇₁N₉O₂₃S).

2 IDENTIFICATION

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

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

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: Nominally 0.5 mg/mL of micafungin from Micafungin for Injection in Diluent prepared as follows. Quantitatively transfer the contents of 1 vial of Micafungin for Injection using Diluent into a suitable volumetric flask to assure the final nominal concentration. Sonication may be needed. Dilute with Diluent to final volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm. For Identification A, use a diode array detector in the range of 200-400 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 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of micafungin (C₅₆H₇₁N₉O₂₃S) in the portion of Micafungin for Injection taken:

                         Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 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 = nominal concentration of micafungin in the Sample solution (mg/mL)

M_r1 = molecular weight of micafungin, 1270.27

M_r2 = molecular weight of micafungin sodium, 1292.27

Acceptance criteria: 95%-115%

4 IMPURITIES

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: Nominally 4 mg/mL of micafungin from Micafungin for Injection in Diluent prepared as follows. Quantitatively transfer the contents of 1 vial of Micafungin for Injection using Diluent into a suitable size volumetric flask to assure the final nominal concentration. Sonication may be needed.

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 for Injection 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-hydroxyethyl]-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.

^c Sodium 5-[(15,2S)-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-exaoxo-9-(4-(5-[4-(pentyloxy)phenyl]isoxazol-3-yl)benzamido)tetracos 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,9S,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,20S,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][1,4,7,10,13,16] hexaazacyclohenicosin-23-yl)-1,2-dihydroxyethyl]-2-hydroxyphenyl sulfate.

5 PERFORMANCE TESTS

UNIFORMITY OF DOSAGE UNITS (905): Meets the requirements

6 SPECIFIC TESTS

6.1 PH (791)

Sample: 10-20 mg/mL

Acceptance criteria: 5.0-7.0

6.2 PARTICULATE MATTER IN INJECTIONS (788), Method 1 Light Obscuration Particle Count Test

Sample: 1 container when tested as directed

Acceptance criteria: Meets the requirements

6.3 BACTERIAL ENDOTOXINS TEST (85)

Meets the requirements

6.4 STERILITY TESTS (71), Test for Sterility of the Product to Be Examined. Membrane Filtration

Meets the requirements

6.5 CONSTITUTED SOLUTION

At the time of use, it meets the requirements of Injections and Implanted Drug Products (1), Product Quality Tests Common to Parenteral Dosage Forms. Specific Tests. Completeness and Clarity of Solutions.

6.6 OTHER REQUIREMENTS

It meets the requirements for Labeling (7), Labels and Labeling for Injectable Products.

7 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve as described in Packaging and Storage Requirements (659), Injection Packaging, Packaging for Constitution. Store at controlled room temperature. Protect from light.

USP REFERENCE STANDARDS (11)

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