Mycophenolate Mofetil

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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C₂₃H₃₁NO₇           433.49

4-Hexenoic acid, 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-, 2-(4-morpholinyl)ethyl ester, (E)-;2-Morpholinoethyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoate

CAS RN: 128794-94-5; UNII: 9242ECW6R0.

1 DEFINITION

Mycophenolate mofetil contains NLT 98.0% and NMT 102.0% of mycophenolate mofetil (C₂₃H₃₁NO₇), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K _{(CN 1-MAY-2020)}

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

Buffer: Triethylamine and water (1:325). Adjust with phosphoric acid to a pH of 5.3.

Mobile phase: Acetonitrile and Buffer (7:13)

Standard solution: 0.4 mg/ml of USP Mycophenolate Mofetil RS in acetonitrile

Sample solution: 0.4 mg/mL of Mycophenolate Mofetil in acetonitrile

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 250 nm

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

Column temperature: 45°

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 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of mycophenolate mofetil (C₂₃H₃₁NO₇) in the portion of Mycophenolate Mofetil 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 = concentration of Mycophenolate Mofetil in the Sample solution (mg/mL)

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

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

ORGANIC IMPURITIES

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

Sample solution: 2 mg/mL of Mycophenolate Mofetil in acetonitrile

System suitability solution: 10 µg/mL each of USP Mycophenolate Mofetil Related Compound A RS and USP Mycophenolate Mofetil Related Compound B. RS in acetonitrile

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 250 nm

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

Column temperature: 45°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 1.5 between mycophenolate mofetil related compound A and mycophenolate mofetil related compound B

Analysis

Sample: Sample solution

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

Result = (r_u /r_T ) × 100

r_u = peak response for each impurity

r_T = sum of all the peak responses

Acceptance criteria: See Table 1. Disregard any peak less than 0.03%.

Table 1

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

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

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

^d 2-Morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate N-oxide.

^e 2-Morpholinoethyl (RS)-(E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-1-(2-morpholinoethoxy)-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate.

^f 2-Morpholinoethyl (Z)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate.

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

^h Methyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate.

5 SPECIFIC TESTS

LOSS ON DRYING (731).

Analysis: Dry a sample under vacuum at 60 for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, and store at 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