Mycophenolate Mofetil for Oral Suspension
DEFINITION
Mycophenolate Mofetil for Oral Suspension is a dry mixture of mycophenolate mofetil and one or more suitable buffers, colors, diluents, and flavors. It contains NLT 90.0% and NMT 110.0% of the labeled amount of mycophenolate mofetil (C23H31NO7).
IDENTIFICATION
• The retention time of the major peak in the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
[Note—Protect solutions from light. ]
Buffer 1:
Pipet 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:
Pipet 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)
Extraction solvent:
Acetonitrile, Buffer 2, and water (13:4:9)
Diluent:
Acetonitrile, Buffer 2, and water (7:4:9)
Mobile phase:
Acetonitrile and Solution A (3:7)
Standard stock solution:
4 mg/mL of USP Mycophenolate Mofetil RS in Extraction solvent. Sonicate to aid the dissolution.
Standard solution:
0.4 mg/mL of USP Mycophenolate Mofetil RS in Diluent, from the Standard stock solution
Sample stock solution:
Constitute Mycophenolate Mofetil for Oral Suspension as directed on the label. Prepare a composite sample by mixing NLT 4 bottles of the constituted Mycophenolate Mofetil for Oral Suspension. Transfer a volume of the composite sample so obtained, equivalent to 800 mg of mycophenolate mofetil, to a 200-mL volumetric flask, and dilute with Extraction solvent to volume.
Sample solution:
Transfer 5.0 mL of the Sample stock solution to a 50-mL volumetric flask, and dilute with Diluent to volume. Pass through a filter of 45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 249 nm
Column:
4.6-mm × 25-cm; 5-µm packing L11
Column temperature:
45
Autosampler temperature:
5
Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C23H31NO7 in the portion of Mycophenolate Mofetil for Oral Suspension 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
• Dissolution 
711
711
[Note—Prepare all solutions in low-actinic glassware. ]
Medium:
0.1 N hydrochloric acid; 900 mL, deaerated
Apparatus 2:
40 rpm
Time:
20 min
Standard solution:
0.278 mg/mL of USP Mycophenolate Mofetil RS in Medium
Sample solution:
Reconstitute Mycophenolate Mofetil for Oral Suspension according to the labeling instructions. Shake well. Use a separate 3-mL syringe for each vessel. Withdraw 2 mL of suspension. Remove air bubbles from the syringe. Adjust the volume to 1.2 mL and accurately weigh the filled syringe. Operate the apparatus, holding the syringe above the surface of the medium, at a location that is halfway between the paddle shaft and the vessel wall. Carefully introduce the sample to the vessel over a 5–10 s period. Weigh the empty syringe and determine the weight of the sample (g). At the time specified, withdraw an aliquot and immediately pass through a suitable filter of 10-µm pore size, discarding the first few mL.
Spectrometric conditions
Mode:
UV
Analytical wavelength:
304 nm
Cell:
0.2 cm
Blank:
Medium
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of mycophenolate mofetil dissolved:
Result = (AU/AS) × (CS/L) × (V1/V2) × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of mycophenolate mofetil in the Standard solution (mg/mL) |
| L | = | = suspension label claim of mycophenolate mofetil (mg/mL) |
| V1 | = | = volume of Medium, 900 (mL) |
| V2 | = | = volume of sample (mL), weight (g) of the sample divided by the density of the suspension (g/mL) |
Tolerances:
NLT 80% (Q) of the labeled amount of mycophenolate mofetil is dissolved.
• Uniformity of Dosage Units 905:
Meets the requirements
905:
Meets the requirements
• Deliverable Volume 698:
Meets the requirements
698:
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. [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. ]
Sensitivity solution:
0.2 µg/mL in Diluent, from the Standard solution
System suitability
Samples:
Standard solution, System suitability solution, and Sensitivity solution
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 Oral Suspension 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 (see Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
[Note—Disregard any unspecified impurity peaks less than 0.05%. ]
Total impurities:
NMT 3.8%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Mycophenolic acida | 0.12 | 1.4 | 3.3 |
| Sorbitol ester of mycophenolic acidb | 0.24 | 0.77 | 0.2 |
| Mycophenolate mofetil | 1.00 | — | — |
| Any individual 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.
b
Sorbitol (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enoate.
|
|||
SPECIFIC TESTS
• pH 791:
Between 6.0 and 7.0, in the suspension constituted as directed in the labeling
791:
Between 6.0 and 7.0, in the suspension constituted as directed in the labeling
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers, and store at controlled room temperature.
• USP Reference Standards 11
11
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 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3971
Pharmacopeial Forum: Volume No. 35(6) Page 1466