Mycophenolate Mofetil Tablets
DEFINITION
Mycophenolate Mofetil Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of mycophenolate mofetil (C23H31NO7).
IDENTIFICATION
• A. Ultraviolet Absorption 
197U
197U
Standard solution and Sample solution:
Use the Standard solution and Sample solution as prepared in the test for Dissolution.
Acceptance criteria:
The UV absorption spectrum of the Standard solution and the Sample solution exhibit maxima and minima at the same wavelength within ±3 nm.
• B.
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
Phosphoric acid solution:
Phosphoric acid and water (3:50)
Triethylamine solution:
Transfer 3 mL of triethylamine to 1000 mL of water. Adjust with Phosphoric acid solution to a pH of 5.3.
Mobile phase:
Acetonitrile and Triethylamine solution (11:9)
Standard solution:
0.125 mg/mL of USP Mycophenolate Mofetil RS in acetonitrile
Sample solution:
Place Tablets, equivalent to 2.5 g of mycophenolate mofetil based on the label claim, into a 1000-mL volumetric flask. Add 100 mL of water, and shake mechanically for a minimum of 15 min. Add 700 mL of acetonitrile, sonicate for 15 min, and shake mechanically for 20 min. Dilute with acetonitrile to volume. Transfer 5.0 mL of this solution to a 100-mL volumetric flask, and dilute with acetonitrile to volume. Pass through a nylon filter of 0.45-µm pore size, and discard the first 5 mL of filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 250 nm
Column:
4.6-mm × 25-cm; 5-µm packing L7
Column temperature:
45
Autosampler temperature:
10 ± 5
± 5
Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of mycophenolate mofetil (C23H31NO7) in the portion of Tablets 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 | = | = nominal concentration of mycophenolate mofetil in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
711
Test 1
Medium:
0.1 N hydrochloric acid; 900 mL
Apparatus 2:
50 rpm
Times:
5 and 15 min
Standard solution:
0.55 mg/mL of USP Mycophenolate Mofetil RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Detector:
UV 304 nm
Path length:
0.1 cm
Blank:
Medium
Analysis
Samples:
Standard solution and Sample soultion
Calculate the percentage of mycophenolate mofetil (C23H31NO7) dissolved:
Result = (AU/AS) × (CS/L) × V × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 900 mL |
Correction factor = (v × P5)/V
| v | = | = volume of solution under test withdrawn (mL) |
| P5 | = | = percentage of mycophenolate dissolved at 5 min |
Correction of the percentage dissolved at 15 min:
Result = Correction factor + percentage dissolved at 15 min
Tolerances:
NLT 75% (Q) of the labeled amount of mycophenolate mofetil (C23H31NO7) is dissolved in 5 min, and NLT 85% of the labeled amount of mycophenolate mofetil (C23H31NO7) is dissolved in 15 min.
Test 2:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium:
0.1 N hydrochloric acid; 900 mL, deaerated
Apparatus 2:
50 rpm
Times:
5 and 15 min
Diluted phosphoric acid:
Transfer 5 mL of phosphoric acid to a 25-mL volumetric flask. Dilute with water to volume.
Buffer:
3.0 mL/L of triethylamine in water. Adjust with Diluted phosphoric acid to a pH tof 5.3.
Mobile phase:
Acetonitrile and Buffer (45:55)
Diluent:
Acetonitrile and Buffer (20:80)
Standard stock solution:
0.56 mg/mL of USP Mycophenolate Mofetil RS in Medium
Standard solution:
0.11 mg/mL of USP Mycophenolate Mofetil RS in Diluent, prepared from the Standard stock solution
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Transfer 5 mL of the filtrate to a 25-mL volumetric flask, and dilute with Diluent to volume.
Chromatographic system
Mode:
LC
Detector:
UV 250 nm
Column:
4.6-mm × 15-cm; 5-µm packing L7
Column temperature:
35
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%
Analysis
Samples:
Standard solution and Sample soultion
Calculate the percentage of mycophenolate mofetil (C23H31NO7) dissolved:
Result = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak area from the Sample solution |
| rS | = | = peak area from the Standard solution |
| CS | = | = concentration of the Standard solution |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 900 mL |
Correction factor = (v × P5)/V
| v | = | = volume of solution under test withdrawn (mL) |
| P5 | = | = percentage of mycophenolate dissolved at 5 min |
Correction of the percentage dissolved at 15 min:
Result = Correction factor + percentage dissolved at 15 min
Tolerances:
NLT 60% (Q) of the labeled amount of mycophenolate mofetil (C23H31NO7) is dissolved in 5 min, and NLT 80% of the labeled amount of mycophenolate mofetil (C23H31NO7) is dissolved in 15 min.
Test 3:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Medium:
0.1 N hydrochloric acid; 900 mL
Apparatus 2:
50 rpm
Times:
5 and 15 min
Standard solution:
0.011 mg/mL of USP Mycophenolate Mofetil RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Dilute 2 mL of the filtrate with Medium to 100 mL.
Detector:
UV 250 nm
Path length:
1 cm
Blank:
Medium
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of mycophenolate mofetil (C23H31NO7) dissolved:
Result = (AU/AS) × (CS/L) × V × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 900 mL |
Correction factor = (v × P5)/V
| v | = | = volume of solution under test withdrawn (mL) |
| P5 | = | = percentage of mycophenolate dissolved at 5 min |
Correction of the percentage dissolved at 15 min:
Result = Correction factor + percentage dissolved at 15 min
Tolerances:
NLT 70% (Q) of the labeled amount of mycophenolate mofetil (C23H31NO7) is dissolved in 5 min, and NLT 85% of the labeled amount of mycophenolate mofetil (C23H31NO7) is dissolved in 15 min.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
• Limit of Degradation Products
Mobile phase, Standard solution, Sample solution, and Chromatographic system:
Proceed as directed in the Assay.
Sensitivity solution:
0.0625 µg/mL of USP Mycophenolate Mofetil RS in acetonitrile
System suitability
Samples:
Standard solution and Sensitivity solution
Suitability requirements
Signal-to-noise ratio:
NLT 10, Sensitivity solution
Tailing factor:
NMT 2, Standard solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
[Note—The run time for the Sample solution is three times that of the retention time of the mycophenolate mofetil peak. ]
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets 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 USP Mycophenolate Mofetil RS 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 Table 1) |
Acceptance criteria:
See Table 1. [Note—Disregard peaks at relative retention times of 1.45 and 2.15. Disregard any peaks less than 0.05%. ]
Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Mycophenolic acida | 0.6 | 1.4 | 1.0 |
| Mycophenolate N-oxide analogb | 0.8 | 1.0 | 0.2 |
| Mycophenolate mofetil | 1.0 | — | — |
| Any single unspecified impurity |
— | 1.0 | 0.1 |
| Total degradation products | — | — | 1.5 |
|
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-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate N-oxide.
|
|||
• Limit of Z-Mycophenolate Mofetil
[Note—Z-Mycophenolate mofetil is 2-morpholinoethyl (Z)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-5-phthalanyl)-4-methyl-4-hexenoate. ]
Triethylamine solution:
Proceed as directed in the Assay.
Mobile phase:
Acetonitrile and Triethylamine solution (7:13)
Standard solution:
0.025 mg/mL of USP Mycophenolate Mofetil RS in acetonitrile
Sensitivity solution:
1.25 µg/mL of USP Mycophenolate Mofetil RS in acetonitrile
Sample solution:
Place Tablets, equivalent to 2.5 g of mycophenolate mofetil based on the label claim, into a 1000-mL volumetric flask. Add 100 mL of water, and shake mechanically for a minimum of 15 min. Add 700 mL of acetonitrile, sonicate for 15 min, and shake mechanically for 20 min. Dilute with acetonitrile to volume. Pass through a nylon filter of 0.45-µm pore size, and discard the first 2 mL of filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 215 nm
Column:
4.6-mm × 15-cm; 3.5-µm packing L7
Column temperature:
60
Flow rate:
1.5 mL/min
Run time:
1.7 times the retention time of the mycophenolate mofetil peak
Injection size:
10 µL
System suitability
Samples:
Standard solution and Sensitivity solution
[Note—The relative retention times for mycophenolate mofetil and Z-mycophenolate mofetil are 1.0 and 1.1, respectively. ]
Suitability requirements
Signal-to-noise ratio:
NLT 10, Sensitivity solution
Tailing factor:
NMT 2.0, Standard solution
Relative standard deviation:
NMT 5.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of Z-mycophenolate mofetil in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of Z-mycophenolate mofetil from the Sample solution |
| rS | = | = peak response of mycophenolate mofetil from the Standard solution |
| CS | = | = concentration of USP Mycophenolate Mofetil RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of mycophenolate mofetil in the Sample solution (mg/mL) |
Acceptance criteria:
NMT 0.10%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed, light-resistant containers, and store at controlled room temperature.
• Labeling:
When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
• USP Reference Standards 11
11
USP Mycophenolate Mofetil RS 
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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 3973
Pharmacopeial Forum: Volume No. 35(4) Page 856