Mycophenolate 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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C₁₇H₁₉NaO₆             342.32

4-Hexenoic acid, 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-, monosodium salt, (E)-;Sodium (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enoate

CAS RN: 37415-62-6.

1 DEFINITION

Mycophenolate Sodium contains NLT 98.0% and NMT 102.0% of mycophenolate sodium (C₁₇H₁₉NaO₆), calculated on the anhydrous basis.

2 IDENTIFICATION

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

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

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Solution A: Acetonitrile, phosphoric acid, and water (100:0.2:900)

Solution B: Acetonitrile, phosphoric acid, and water (800:0.2:200)

Mobile phase: See Table 1. Return to original conditions, and re-equilibrate the system.

Table 1

Diluent: Methanol and water (1:9)

Standard solution: 0.08 mg/mL of USP Mycophenolate Sodium RS in Diluent. Protect from light.

Sample solution: 0.08 mg/mL of Mycophenolate Sodium in Diluent. Protect from light.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 216 nm

Column: 3-mm × 25-cm; 5-µm packing L1

Column temperature: 50°

Flow rate: 0.8 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 0.73%

Tailing factor: 0.7–1.5

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of mycophenolate sodium (C₁₇H₁₉NaO₆) in the portion of Mycophenolate Sodium taken:

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

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

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

C_u = concentration of Mycophenolate Sodium in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

ORGANIC IMPURITIES

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Mobile phase, Diluent, Standard solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability stock solution 1: 0.02 mg/mL of USP Mycophenolate Mofetil Related Compound B.RS prepared as follows. Transfer USP Mycophenolate Mofetil Related Compound B RS to a suitable volumetric flask and dilute in methanol equivalent to 10% of the final volume, and then dilute with water to volume.

System suitability stock solution 2: Transfer 4.0 mL of System suitability stock solution 1 to a 100-mL volumetric flask and dilute with Diluent to volume.

System suitability solution: 0.8 µg/mL of USP Mycophenolate Mofetil Related Compound B RS and 0.08 mg/mL of USP Mycophenolate Sodium RS prepared by dissolving a suitable amount of USP Mycophenolate Sodium RS in System suitability stock solution 2

Sensitivity solution: 0.024 µg/mL of USP Mycophenolate Sodium RS in Diluent from Standard solution

System suitability

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

Suitability requirements

Resolution: NLT 1.5 between the mycophenolate mofetil related compound B and mycophenolate peaks, System suitability solution

Relative standard deviation: NMT 0.73%, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Mycophenolate Sodium taken:

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

r_u = peak response of each impurity from the Sample solution

r_s = peak response of mycophenolate from the Standard solution

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

C_u = concentration of Mycophenolate Sodium in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. Disregard any impurity peak less than 0.05%.

Table 2

^a (RS)-7-Hydroxy-5-methoxy-4-methyl-6-[2-(5-methyl-2-oxo-tetrahydrofuran-5-yl)ethyl]-3H-isobenzofuran-1-one.

5 SPECIFIC TESTS

SODIUM CONTENT

Standard stock solution: Use commercially available sodium atomic absorption spectroscopy standard solution of 1000 µg/mL of sodium in 0.5 M nitric acid.

Diluent: Transfer 3 mL of nitric acid to a 250-mL volumetric flask, and dilute with water to volume.

Standard solution A: 6.0 µg/mL of sodium in Diluent from Standard stock solution

Standard solution B: 9.0 µg/mL of sodium in Diluent from Standard stock solution

Standard solution C: 12.0 µg/mL of sodium in Diluent from Standard stock solution

Sample solution: 0.14 mg/mL of Mycophenolate Sodium prepared as follows. Weigh 30-40 mg of Mycophenolate Sodium into a digestion vessel, add 3 mL of nitric acid and digest at 150° for 5 h. Allow to cool, transfer the digestion solution to a 250-mL volumetric flask, and dilute with water to volume.

Instrumental conditions

(See Atomic Absorption Spectroscopy (852).)

Mode: Atomic absorption spectrophotometry

Analytical wavelength: 589.0 nm

Lamp: Sodium hollow-cathode

Flame: Air-acetylene

Blank: Diluent

System suitability

Sample: Standard solution B

Suitability requirements

Relative standard deviation: NMT 5% for absorbance from three readings

Analysis

Samples: Standard solutions, Sample solution, and Blank

Plot the absorbances of the Blank and Standard solutions versus their concentrations of sodium (0, 6.0, 9.0, and 12.0 µg/mL), and draw a calibration curve best fitting the four points. From the graph so obtained, determine the concentration, in µg/ml, of sodium in the Sample solution.

Calculate the percentage of sodium in the portion of Mycophenolate Sodium taken.

Result = F × (C_s /C_u ) × 100

F = conversion factor (0.001 mg/µg)

C_s = concentration of sodium in the Sample solution (µg/mL)

C_u = concentration of Mycophenolate Sodium in the Sample solution (mg/mL)

Acceptance criteria: 5.7%–7.7% on the anhydrous basis

Change to read:

X-RAY POWDER DIFFRACTION (941) (CN 1-MAY-2022): Its X-ray diffraction pattern conforms to that of USP Mycophenolate Sodium RS. similarly determined.

WATER DETERMINATION, Method la(921): NMT 1.5%

MICROBIAL ENUMERATION TESTS (61) and TESTS FOR SPECIFIED MICROORGANISMS (62): The total aerobic microbial limit does not exceed 10³ cfu/g. The total yeasts and molds count does not exceed 10² cfu/g.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers. Protect from light.

USP Reference Standards 〈11〉

USP Mycophenolate Mofetil Related Compound B RS

(RS)-7-Hydroxy-5-methoxy-4-methyl-6-[2-(5-methyl-2-oxo-tetrahydrofuran-5-yl)ethyl]-3H-isobenzofuran-1-one.

C₁₇H₂₀O₆           320.34

USP Mycophenolate Sodium RS