Mycophenolate Mofetil
(mye'' koe fen' oh late moe' fe til).
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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     [115007-34-6].
DEFINITION
Mycophenolate Mofetil contains NLT 98.0% and NMT 102.0% of C23H31NO7, calculated on the dried basis.
IDENTIFICATION
•  B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
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:  1.0 mg/mL of USP Mycophenolate Mofetil RS in acetonitrile
Sample solution:  1 mg/mL of Mycophenolate Mofetil in acetonitrile
Chromatographic system 
Mode:  LC
Detector:  UV 250 nm
Column:  4.6-mm × 15-cm; packing L7
Temperature:  45
Flow rate:  1.5 mL/min
Injection size:  10 µL
System suitability 
Sample:  Standard solution
Suitability requirements 
Column efficiency:  NLT 8000 theoretical plates
Tailing factor:  NMT 1.5
Relative standard deviation:  NMT 2.0%
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of C23H31NO7 in the portion of Mycophenolate Mofetil taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== concentration of USP Mycophenolate Mofetil RS in the Standard solution (mg/mL)
CU== concentration of Mycophenolate Mofetil in the Sample solution (mg/mL)
Acceptance criteria:  98.0%–102.0% on the dried basis
IMPURITIES
Inorganic Impurities 
•  Residue on Ignition 281: NMT 0.1%
•  Heavy Metals, Method II 231: NMT 20 ppm
Organic Impurities 
•  Procedure 1
Buffer, Mobile phase, and Sample solution:  Prepare as directed in the Assay.
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 
Mode:  LC
Detector:  UV 250 nm
Column:  4.6-mm × 25-cm; packing L7
Temperature:  45
Flow rate:  1.5 mL/min
Injection size:  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 = (rU/rT) × 100
rU== peak response for each impurity
rT== sum of all the peak responses
Acceptance criteria 
Individual impurities:  See Impurity Table 1.
Total impurities:  NMT 0.70%
Impurity Table 1
Name Relative
Retention
Time
Acceptance
Criteria,
NMT (%)
Mycophenolic acida 0.33 0.50
Mycophenolate mofetil related compound Ab 0.45 0.10
Mycophenolate mofetil related compound Bc 0.49 0.10
N-Oxide analogd 0.60 0.10
1-Morpholinoethoxy analoge 0.86 0.10
Mycophenolate mofetil 1.0
O-Methyl analogf 1.2 0.10
Methyl mycophenolateg 1.5 0.10
Any single unspecified impurity 0.10
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-isobenzofuranyl-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 (E)-6-(1,3-dihydro-4,6-dimethoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate.
g  Methyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate.
[Note—Disregard any unknown peak less than 0.03%. ]
SPECIFIC TESTS
•  Loss on Drying 731: Dry a sample in a vacuum at 60 for 3 h: it loses NMT 0.5% of its weight.
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in tight containers, and store at room temperature.
•  USP Reference Standards 11
USP Mycophenolate Mofetil RS Click to View Structure
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.
    C23H31NO7        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-isobenzofuranyl-1-one.
    C17H20O6        320.34
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USP35–NF30 Page 3967
Pharmacopeial Forum: Volume No. 35(1) Page 89