Mupirocin Calcium

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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C₅₂H₈₆CaO₁₈ · 2H₂O       1075.35 _{(ERR 1-May-2022)}

Nonanoic acid, 9-[[3-methyl-1-oxo-4-[tetrahydro-3,4-dihydroxy-5-[[3-(2-hydroxy-1-methylpropyl)oxiranyl]methyl]-2H-pyran-2-yl]-2-butenyl)oxy-. calcium salt (2:1), dihydrate, [2S-[2(E),3β,48,5α[2R*,3R*(1R*,2R*)]]]; (E,2S,3R,4R,5S)-5-[(2S,3S,4S,5S)-2,3-Epoxy-5-hydroxy-4-methylhexyl tetrahydro-3,4-dihydroxy-ẞ-methyl-2H-pyran-2-crotonic acid, ester with 9-hydroxynonanoic acid, calcium salt (2:1), dihydrate

CAS RN: 115074-43-6; UNII: RG3812P540.

1 DEFINITION

Mupirocin Calcium contains the equivalent of NLT 865 µg/mg and NMT 936 µg/mg of mupirocin (C₂₆H₄₄O₉).

2 IDENTIFICATION

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

Sample: Do not grind extensively.

Acceptance criteria: Meets the requirements

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. Calcium

Sample solution: Mupirocin Calcium in methanol (1:20)

Acceptance criteria: Meets the requirements

3 ASSAY

PROCEDURE

Buffer: 7.7 g/L of ammonium acetate in water. Adjust with acetic acid, glacial to a pH of 5.7 before diluting to the final volume.

Mobile phase: Tetrahydrofuran and Buffer (32:68)

Standard solution: 0.125 mg/mL of USP Mupirocin Lithium RS prepared as follows. Transfer a suitable amount of USP Mupirocin Lithium RS

to a suitable volumetric flask, dissolve in methanol using 2.5% of the final volume, and dilute with Buffer to volume.

System suitability solution: Adjust 10 mL of the Standard solution with 6 N hydrochloric acid to a pH of 2.0, allow to stand for 20 h, and adjust

with 5 N sodium hydroxide to a pH of 4.0.

Sample solution: 0.125 mg/mL of Mupirocin Calcium prepared as follows. Transfer a suitable amount of Mupirocin Calcium to a suitable volumetric flask, dissolve in 2.5% of the final volume of methanol, and dilute with Buffer to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 230 nm.

Column: 4.6-mm x 25-cm; 5-µm packing 12

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Samples: Standard solution and System suitability solution

Suitability requirements

Resolution: NLT 7.0 between the mupirocin pyranyl analog and mupirocin, System suitability solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the quantity, in µg/mg, of mupirocin (C₂₆H₄₄O₉) in the portion of Mupirocin Calcium taken:

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

r_u = peak area of mupirocin from the Sample solution

r_s = peak area of mupirocin from the Standard solution

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

C_u = concentration of Mupirocin Calcium in the Sample solution (mg/mL)

P = potency of mupirocin in USP Mupirocin Lithium RS (µg/mg)

Acceptance criteria: 865–936 µg/mg

4 IMPURITIES

CHLORIDE AND SULFATE (221), Chloride

4.1 Analysis: Dissolve 50 mg in a mixture of 1 mL of 2N nitric acid and 15 mL of methanol. Add 1 mL of silver nitrate TS.

Acceptance criteria: The turbidity does not exceed that produced by 0.70 mL of 0.020 N hydrochloric acid (0.5%).

Change to read:

4.2 ORGANIC IMPURITIES

Buffer: Prepare as directed in the Assay.

Solution A: 13.6 g/L of sodium acetate in water. Adjust with acetic acid, glacial to a pH of 4.0 before diluting to the final volume.

Mobile phase: Tetrahydrofuran and Buffer (30:70)

Diluent: Methanol and Solution A (1:1)

Standard solution: 0.125 mg/mL of USP Mupirocin Lithium RS in Diluent

System suitability solution: Adjust 10 mL of the Standard solution with 6 N hydrochloric acid to a pH of 2.0, allow to stand for 20 h, and adjust with 5 N sodium hydroxide to a pH of 4.0.

Sensitivity solution: 0.0025 mg/mL of mupirocin lithium prepared from the Standard solution.

Sample solution: 5 mg/mL of Mupirocin Calcium in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm x 25-cm; 5-µm packing L7

Autosampler temperature: 5°

Flow rate: 1 mL/min.

Injection volume: 20 µL

Run time: NLT 3 times the retention time of mupirocin

System suitability

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

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

Suitability requirements

Resolution: NLT 7.0 between the mupirocin pyranyl analog and mupirocin, System suitability solution

Tailing factor: NMT 2 for the mupirocin peak, Standard solution

Relative standard deviation: NMT 5% for the mupirocin peak, Standard solution

Signal-to-noise ratio: NLT 10 for the mupirocin peak, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Mupirocin Calcium taken:

Result = (r_u /r_s ) × (C_s /C_u ) × P × F × 100

r_u = peak area of any individual impurity from the Sample solution

r_s = peak area of mupirocin from the Standard solution

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

C_u = concentration of Mupirocin Calcium in the Sample solution (mg/mL)

P = potency of mupirocin in USP Mupirocin Lithium RS (µg/mg)

F = conversion factor, 0.001 mg/µg

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

Table 1

^a 7-{(E)-4-[(2S,3R,4R,5S)-3,4-Dihydroxy-5-({(2S,3S)-3-[(2S,3S)-3-hydroxybutan-2-yl]oxiran-2-yl}methyl)tetrahydro-2H-pyran-2-yl]-3-methylbut-2- enoyloxy}heptanoic acid.

^b 9-{(E)-4-[(2R,3aS,6S,7S)-2-{(1RS,2S,3S)-1,3-Dihydroxy-2-methylbutyl}-7-hydroxyhexahydro-2H-furo[3,2-c]pyran-6-yl]-3-methylbut-2- enoyloxy}nonanoic acid. _{(ERR 1-May-2022)}

^c 9-{(E)-4-[(2R,3RS,4aS,7S,8S,8aR)-3,8-Dihydroxy-2-{(2S,3S)-3-hydroxybutan-2-yl}octahydropyrano[3,2-c]pyran-7-yl]-3-methylbut-2- enoyloxy}nonanoic acid.

^d (E)-9-{(E)-4-[(2S,3R,4R,5S)-3,4-Dihydroxy-5-({(2S,3S)-3-[(2S,3S)-3-hydroxybutan-2-yl]oxiran-2-yl}methyl)tetrahydro-2H-pyran-2-yl]-3- methylbut-2-enoyloxy}non-4-enoic acid.

^e 9-{(E)-3-Methyl-4-[(2S,3R,4S,5R)-3,4,5-trihydroxy-5-({(2S,3S)-3-[(2S,3S)-3-hydroxybutan-2-yl]oxiran-2-yl}methyl)tetrahydro-2H-pyran-2-yl]but2-enoyloxy}nonanoic acid.

^f 9-((E)-4-{(2S,3R,4R,5S)-3,4-Dihydroxy-5-[(4R,5S,E)-5-hydroxy-4-methylhex-2-enyl]tetrahydro-2H-pyran-2-yl}-3-methylbut-2-enoyloxy)nonanoic acid.

^g 11-{(E)-4-[(2S,3R,4R,5S)-3,4-Dihydroxy-5-({(2S,3S)-3-[(2S,3S)-3-hydroxybutan-2-yl]oxiran-2-yl}methyl)tetrahydro-2H-pyran-2-yl]-3-methylbut2-enoyloxy}undecanoic acid.

5 SPECIFIC TESTS

OPTICAL ROTATION (781S), Procedures, Specific Rotation

Sample solution: 50 mg/mL in methanol

Acceptance criteria: -16° to -20°

WATER DETERMINATION (921), Method /: 3.0%-4.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers. Store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Mupirocin Calcium RS

USP Mupirocin Lithium RS

Lithium 9-((E)-4-[(2S,3R,4R,5S)-3,4-dihydroxy-5-(((2S,3S)-3-[(2S,3S)-3-hydroxybutan-2-yl)oxiran-2-yl)methyl)tetrahydro-2H-pyran-2-yl]-3-methylbut-2-enoyloxy)nonanoate.

C₂₆H₄₃LiO₉         506.56