1. Drug Substance General Information (ICH 3.2.S.1)

1.1. Nomenclature (ICH 3.2.S.1.1)

International non-proprietary name: Mycophenolate mofetil (Brand Name: CellCept, MMF)

Compendial name: Mycophenolate mofetil

Chemical name: 2-morpholinoethyl (E)-6-(1, 3-dihydro-4-hydroxy-6- methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate

Arasto’s code: MYC

CAS Registry Number: [128794-94-5]

Official Pharmacopoeia Monograph: USP 44

1. Drug Substance General Information (ICH 3.2.S.1)

1.2. Structure (ICH 3.2.S.1.2)

  1. Drug Substance General Information (ICH 3.2.S.1)

1.3.  General Properties (ICH 3.2.S.1.3)

Mycophenolate mofetil is a white to off-white crystalline powder. It is slightly soluble in water (43 μg/mL at pH 7.4); the solubility increases in acidic medium (4.27 mg/mL at pH 3.6). It is freely soluble in dimethyl sulfoxide, tetrahydrofuran, acetone, acetonitrile, dichloromethane, and ethyl acetate; soluble in methanol and propylene carbonate; sparingly soluble in anhydrous ethanol; slightly soluble in isopropanol and diethyl ether; and very slightly soluble in hexane. The apparent partition coefficient in 1-octanol/water (pH 7.4) buffer solution is 238. The pKa values for Mycophenolate mofetil are 5.6 for the Morpholino moiety and 8.5 for the phenolic moiety (for further information see, PMs/CellCept/CellCept_PM_E.pdf.

The impurities provided in the following table represent Secondary Reference Standards (SRS) that are prepared in-house by synthesis or by isolation. Each SRS has undergone extensive characterization (IR, UV, 1HNMR, 13CNMR. Mass Spec) and determination of its purity and assay (HPLC). For specification of the SRS of those products that have a monograph, the SRS is compared with a pharmacopoeia Primary Reference Standard (UV, HPLC retention time). For specification of those products that do not have a monograph (known as House Primary Standard), we compare their UV ε or ג /max, IR major absorptions, 1HNMR d(ppm), 13CNMR d(ppm) or HPLC retention time with values reported in the chemical literature for these compounds.

Mycophenolate mofetil USP Related Compounds

Arasto CodeUSP CodeChemical nameStructure
Mycophenolate mofetil related

compound A

Mycophenolate mofetil related

compound A

2-Morpholinoethyl (E)-6-(1,3-dihydro-



Mycophenolate mofetil related

compound B

Mycophenolate mofetil related

compound B


isobenzofuran-1-one, Mycophenolic acid lactone

5. Primary and Secondary Reference Standard (ICH 3.2.S.5)

5.1. Active Pharmaceutical Ingredient

Primary Reference Standard for Mycophenolate mofetil is available from United States Pharmacopoeia. We will use a House Primary Standard (previously referred to as Working Standard) for direct control of all batches of Mycophenolate mofetil.

As per ICH (Q7, 11.1) and ICH (Q6, 2.11, 3.2, 3.3) House Primary Standards, which include the API and its Related Compounds, must be examined for their proof of structure (characterization), assay and purity and specification (identification by comparison). Furthermore, ICH Guideline on the Preparation of Common Technical Document (Q4M) requires that the data obtained from characterization, assay and purity and specification must be included in section 3.2.S.3.2 for Related Compounds (already discussed in that section) and section 3.2.S.5 of the DMF for the API. To this end, the House Primary Standard of the API Mycophenolate mofetil has undergone extensive characterization (UV, IR, 1HNMR, 13CNMR, Mass Spec) to assure its structure, assay and purity (HPLC and/or titration) and specification.

The House Primary Standard for Mycophenolate mofetil was produced from a released batch of Mycophenolate mofetil by subjecting it to an additional crystallization from the final solvent system used in the production of the API to avoid the possibility of other polymorph formation. It was crystallized twice more to ensure high level of purity.


Product: Mycophenolate MofetilCAS No.: 128794-94-5Spec. No.: APC-QC-SPEC-386-00
Issue Date: Apr, 2023Valid up to: Apr, 2024Reference: USP44


DescriptionWhite or almost white, crystalline powder. Its melting range is between 94° and 98°.
SolubilityFreely soluble in acetone; soluble in methanol; sparingly soluble in dehydrated alcohol; slightly soluble in water.
IdentificationA) Infrared Spectroscopy

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

Loss on dryingNMT 0.5%
Residue on ignitionNMT 0.1%
Residual solventsMethanol: Max. 3000 ppm (Class II)

Acetone: Max. 5000 ppm (Class III)

Toluene: Max. 890ppm (Class II)

Organic impurities (HPLC)Mycophenolic Acid: NMT 0.50 %

Mycophenolate Mofetil related compound A: NMT 0.10 %

Mycophenolate Mofetil related compound B: NMT 0.10 %

N-Oxide analog: NMT 0.10 %

1-Morpholineoethoxy analog: NMT 0.10 %

Z- Mycophenolate Mofetil: NMT 0.10 %

O-Methyl analog: NMT 0.10 %

Methyl Mycophenolate: NMT 0.10 %

Any single unspecified impurity: NMT 0.10 %

Total impurities: NMT 0.70 %

Assay (HPLC)98.0% to 102.0% (on the dried basis)
Prepared by: M. Shahbazi, B.Sc.Chem.Checked by: A. Forghani, B.Sc.Chem.
Approved by: F. Javadizadeh, M.Sc.Chem.
Storage: Preserve in tight containers, and store at room temperature.