Mycophenolate Mofetil 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

Mycophenolate mofetil for Injection contains an amount of Mycophenolate Mofetil Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of mycophenolate mofetil (C₂₃H₃₁NO₇).

2 IDENTIFICATION

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A _{(USP 1-MAY-2019)} The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

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B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay _{(USP 1-May-2019)}

3 ASSAY

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PROCEDURE

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Buffer 1: Transfer 10 mL of triethylamine to a 1000-mL volumetric flask containing about 950 mL of water and mix. Adjust with phosphoric acid to a pH of 7.2, and dilute with water to volume.

CIAL Buffer 2: Transfer 10 mL of triethylamine to a 1000-mL volumetric flask containing about 950 ml of water and mix. Adjust with phosphoric acid to a pH of 3.0, and dilute with water to volume.

Solution A: Buffer 1 and water (4:9)

Diluent: Acetonitrile, Buffer 2, and water (7:4:9)

Mobile phase: Acetonitrile and Solution A (3:7)

Standard stock solution: 1.0 mg/mL of USP Mycophenolate Mofetil RS in Diluent prepared as follows. Transfer a known quantity of USP Mycophenolate Mofetil RS to a suitable volumetric flask, add acetonitrile equivalent to about 10% of the final volume, sonicate for about 5 min or until the solid dissolves, and dilute with Diluent to volume.

Standard solution: 0.4 mg/mL of USP Mycophenolate Mofetil RS in Diluent from Standard stock solution

Sample stock solution: Nominally equivalent to 10 mg/mL of mycophenolate mofetil prepared as follows. Constitute each of the containers of Mycophenolate Mofetil for Injection with 14 mL of 5% dextrose injection. Quantitatively transfer the contents of all vials, the combined contents of which are equivalent to about 2 g of mycophenolate mofetil, to a 200-mL volumetric flask, and dilute with water to volume.

Sample solution: Nominally equivalent to 0.4 mg/mL of mycophenolate mofetil in Diluent from Sample stock solution

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 249 nm. For Identification B, use a diode array detector in the range of 200-400 nm _{(USP 1-May-2019)}

Column: 4.6-mm x 25-cm; 5-µm packing L11

Temperatures

Autosampler: 5°

Column: 45^o

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of mycophenolate mofetil (C₂₃H₃₁NO₇) in the portion of Mycophenolate Mofetil for Injection 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 Mofetil RS in the Standard solution (mg/mL)

C_u = nominal concentration of mycophenolate mofetil in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

UNIFORMITY OF DOSAGE UNITS (905): Meets the requirements

5 IMPURITIES

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ORGANIC IMPURITIES

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

System suitability solution: 0.01 mg/mL of USP Mycophenolate Mofetil Related Compound A RS and 0.01 mg/mL of USP Mycophenolate

Mofetil Related Compound B RS in Diluent

Sensitivity solution: 0.2 µg/mL in Diluent from the Standard solution

System suitability

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

[NOTE-The relative retention times for mycophenolate mofetil related compound A and mycophenolate mofetil related compound B are 0.40. and 0.46, respectively, measured with respect to mycophenolate mofetil.]

Suitability requirements

Resolution: NLT 2.0 between mycophenolate mofetil related compound A and mycophenolate mofetil related compound B, System

suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

[NOTE-The run time for the Sample solution is NLT 1.5 times the retention time of the mycophenolate mofetil peak.]

Calculate the percentage of each impurity in the portion of Mycophenolate Mofetil for Injection taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (1/F) × 100

r_u = peak response of each individual impurity from the Sample solution

r_s = peak response of mycophenolate mofetil from the Standard solution

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

C_u = nominal concentration of mycophenolate mofetil in the Sample solution (mg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.05%. _{(USP 1-May-2019)}

Table 1

^a (E)-6-(1,3-Dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid.

6 SPECIFIC TESTS

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BACTERIAL ENDOTOXINS TEST (85): Meets the requirements _{(USP 1-May-2019)}

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STERILITY TESTS (71): Meets the requirements

_{(USP 1-May-2019)}

WATER DETERMINATION (921), Method I. Method la: NMT 1.0%

PH (791): 2.7-4.1, in a reconstituted solution

PARTICULATE MATTER IN INJECTIONS (788): Meets the requirements for small-volume injections

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

7 ADDITIONAL REQUIREMENTS

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

USP REFERENCE STANDARDS (11)

USP Mycophenolate Mofetil RS

USP Mycophenolate Mofetil Related Compound A RS

2-Morpholinoethyl (E)-6-(1,3-dihydro-4,6-dihydroxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate.

C₂₂H₂₉NO₇               419.47

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