Mycophenolate Mofetil
433.494-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].» Mycophenolate Mofetil contains not less than 98.0 percent and not more than 102.0 percent of C23H31NO7, calculated on the dried basis.
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.
USP Mycophenolate Mofetil Related Compound B RS.
11—
USP Mycophenolate Mofetil RS
.
USP Mycophenolate Mofetil Related Compound A RS.
USP Mycophenolate Mofetil Related Compound B RS.
Identification—
Melting range, Class Ia 741:
between 94
and 98, but the range between beginning and end of melting does not exceed 2.5.
741:
between 94 and 98, but the range between beginning and end of melting does not exceed 2.5.
Loss on drying 731—
Dry it at 60 for 3 hours: it loses not more than 0.5% of its weight.
731—
Dry it at 60 for 3 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281:
not more than 0.1%.
281:
not more than 0.1%.
Heavy metals, Method II 231:
0.002%.
231:
0.002%.
Related compounds—
0.3% Triethylamine phosphate buffer and Mobile phase—
Prepare as described in the Assay.
System suitability solution—
Dissolve accurately weighed quantities of USP Mycophenolate Mofetil Related Compound A RS and USP Mycophenolate Mofetil Related Compound B RS in acetonitrile to obtain a solution having a known concentration of about 10 µg per mL each of USP Mycophenolate Mofetil Related Compound A RS and USP Mycophenolate Mofetil Related Compound B RS, and mix.
Test solution—
Use the Assay preparation.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 250-nm detector and a 4.6-mm × 15-cm column that contains packing L7. The flow rate is about 1.5 mL per minute. The column temperature is maintained at 45. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between mycophenolate mofetil related compound A and mycophenolate mofetil related compound B is not less than 1.5.
621)—
The liquid chromatograph is equipped with a 250-nm detector and a 4.6-mm × 15-cm column that contains packing L7. The flow rate is about 1.5 mL per minute. The column temperature is maintained at 45. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between mycophenolate mofetil related compound A and mycophenolate mofetil related compound B is not less than 1.5.
Procedure—
Inject a volume (about 10 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the peak responses. Calculate the percentage of each impurity in the portion of Mycophenolate Mofetil taken by the formula:
100(rI / rs)
in which rI is the peak response for each impurity; and rs is the sum of the responses of all peaks.
| Related Compound | Relative Retention Time |
Limit (%) |
| Mycophenolic acid1 | about 0.33 | 0.5 |
| Mycophenolate mofetil related compound A2 | about 0.45 | 0.1 |
| Mycophenolate mofetil related compound B3 | about 0.49 | 0.1 |
| N-Oxide analog4 | about 0.60 | 0.1 |
| 1-Morphololinoethoxy analog5 | about 0.86 | 0.1 |
| O-Methyl analog6 | about 1.2 | 0.1 |
| Methyl mycophenolate7 | about 1.5 | 0.1 |
| Total specified impurities | — | 0.5 |
| Individual unknown impurities | — | 0.1 |
| Total unknown impurities | — | 0.1 |
| Total impurities | — | 1.0 |
|
1
(E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoic acid.
|
||
|
2
2-Morpholinoethyl (E)-6-(1,3-dihydro-4,6-dihydroxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate.
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|
3
(RS)-7-hydroxy-5-methoxy-4-methyl-6-[2-(5-methyl-2-oxo-tetrahydrofuran-5-yl)ethyl]-3H-isobenzofuranyl-1-one.
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|
4
2-Morpholinoethyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate N-oxide.
|
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|
5
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.
|
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|
6
2-Morpholinoethyl (E)-6-(1,3-dihydro-4,6-dimethoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate.
|
||
|
7
Methyl (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate.
|
||
Assay—
0.3% Triethylamine phosphate buffer—
Add 4 mL of triethylamine to 1300 mL of water. Adjust with phosphoric acid to a pH of 5.3.
Mobile phase—
Prepare a suitable mixture of 0.3% Triethylamine phosphate buffer and acetonitrile (65:35). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard preparation—
Dissolve an accurately weighed quantity of USP Mycophenolate Mofetil RS in acetonitrile, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 1.0 mg per mL.
Assay preparation—
Transfer about 50 mg of mycophenolate mofetil, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with acetonitrile to volume, and mix.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 250-nm detector and a 4.6-mm × 15-cm column that contains packing L7. The flow rate is about 1.5 mL per minute. The column temperature is maintained at 45. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 8000 theoretical plates; the tailing factor is not more than 1.5; and the relative standard deviation for replicate injections is not more than 1.0%.
621)—
The liquid chromatograph is equipped with a 250-nm detector and a 4.6-mm × 15-cm column that contains packing L7. The flow rate is about 1.5 mL per minute. The column temperature is maintained at 45. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 8000 theoretical plates; the tailing factor is not more than 1.5; and the relative standard deviation for replicate injections is not more than 1.0%.
Procedure—
Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C23H31NO7 in the portion of Mycophenolate Mofetil taken by the formula:
50C(rU / rS)
in which C is the concentration, in mg per mL, of USP Mycophenolate Mofetil RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
Chromatographic Column—
| Topic/Question | Contact | Expert Committee |
| Monograph | Feiwen Mao, M.S.
Scientist 1-301-816-8320 |
(MDOOD05) Monograph Development-Ophthalmics Oncologics and Dermatologicals |
| Reference Standards | Lili Wang, Technical Services Scientist 1-301-816-8129 RSTech@usp.org |
USP32–NF27 Page 3015
Pharmacopeial Forum: Volume No. 33(5) Page 924
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.