Mycophenolate Mofetil for Injection
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).
IDENTIFICATION
• 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
[Note—Protect solutions from light. ]
Buffer 1:
Transfer 10 mL of triethylamine into 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.
Buffer 2:
Transfer 10 mL of triethylamine into 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:
Transfer a known quantity of USP Mycophenolate Mofetil RS in a suitable volumetric flask, add acetonitrile equivalent to about 10% of the final volume, and sonicate for about 5 min or until the solid dissolves. Dilute with Diluent to volume to obtain a solution containing a known concentration of 1.0 mg/mL of USP Mycophenolate Mofetil RS.
Standard solution:
0.4 mg/mL of USP Mycophenolate Mofetil RS in Diluent, from Standard stock solution
Sample solution:
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. Transfer 4.0 mL of this solution to a 100-mL volumetric flask, and dilute with Diluent to volume.
Chromatographic system
Mode:
LC
Detector:
UV 249 nm
Column:
4.6-mm × 25-cm; 5-µm packing L11
Temperature
Column:
45
Autosampler:
5
Flow rate:
1.5 mL/min
Injection size:
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 C23H31NO7 in the portion of Mycophenolate Mofetil for Injection taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of mycophenolate mofetil in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of mycophenolate mofetil in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Uniformity of Dosage Units 
905
:
Meets the requirements
905:
Meets the requirements
IMPURITIES
Organic Impurities
[Note—Protect solutions from light. ]
• Procedure
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
Signal-to-noise ratio:
NLT 10, Sensitivity solution
Tailing factor:
NMT 2.0, Standard solution
Relative standard deviation:
NMT 2.0%, Standard 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 = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of each individual impurity from the Sample solution |
| rS | = | = peak response of mycophenolate mofetil from the Standard solution |
| CS | = | = concentration of mycophenolate mofetil in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of mycophenolate mofetil in the Sample solution (mg/mL) |
| F | = | = relative response factor for each individual impurity (see Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1. [Note—Disregard any impurity peak less than 0.05%. ]
Total impurities:
NMT 1.35%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Mycophenolic acida | 0.12 | 1.4 | 1.1 |
| Mycophenolate mofetil | 1.00 | — | — |
| Any unspecified impurity | — | 1.0 | 0.1 |
|
a
(E)-6-(1,3-Dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid.
|
|||
SPECIFIC TESTS
• Bacterial Endotoxins 85:
Contains NMT 0.4 USP Endotoxin Unit/mg of mycophenolate mofetil
85:
Contains NMT 0.4 USP Endotoxin Unit/mg of mycophenolate mofetil
• Sterility Tests 71:
Meets the requirements when tested as directed in Test for Sterility of the Product to be Examined, Membrane Filtration
71:
Meets the requirements when tested as directed in Test for Sterility of the Product to be Examined, Membrane Filtration
• Water Determination, Method Ia 921:
NMT 1.0%
921:
NMT 1.0%
• pH 791:
Between 2.7 and 4.1, in a reconstituted solution
791:
Between 2.7 and 4.1, in a reconstituted solution
• Particulate Matter 788:
Meets the requirements for small-volume injections
788:
Meets the requirements for small-volume injections
• Constituted Solution:
At the time of use, meets the requirements under Injections 1, Constituted Solutions
1, Constituted Solutions
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers and store at controlled room temperature.
• USP Reference Standards 11
11
USP Endotoxin RS
USP Mycophenolate Mofetil RS 
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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
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
(RS)-7-Hydroxy-5-methoxy-4-methyl-6-[2-(5-methyl-2-oxo-tetrahydrofuran-5-yl)ethyl]-3H-isobenzofuranyl-1-one.
C17H20O6 320.34
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Feiwen Mao, M.S.
Senior Scientific Liaison 1-301-816-8320 |
(SM32010) Monographs - Small Molecules 3 |
| 85 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 71 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3970
Pharmacopeial Forum: Volume No. 35(6) Page 1464