Mycophenolate Mofetil Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Mycophenolate mofetil Tablets contain NLT 94.0% and NMT 105.0% of the labeled amount of mycophenolate mofetil (C₂₃H₃₁NO₇).

2 IDENTIFICATION

Change to read:

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay _{(USP 1-Aug-2023)}

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

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 (55:45)

Standard solution: 0.125 mg/mL of USP Mycophenolate Mofetil RS in acetonitrile

Sample stock solution: Nominally 2.5 mg/mL of mycophenolate mofetil prepared as follows. Transfer Tablets, equivalent to 2.5 g of mycophenolate mofetil, to 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. _{(USP 1-Aug-2023)}

Sample solution: Nominally 0.125 mg/mL of mycophenolate mofetil in acetonitrile from Sample stock solution. Pass through a nylon filter of 0.45-µm pore size and discard the first 5 mL of the filtrate _{(USP 1-Aug-2023)}

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 250 nm. For Identification A, use a diode array detector in the range of 200-400 nm. _{(USP 1-Aug-2023)}

Column: 4.6-mm x 25-cm; 5-µm packing LZ

Temperatures

Column: 45°

Autosampler: 10±5°

Flow rate: 1.5 mL/min

Injection volume: 20 µL

Run time: NLT 3 times the retention time of mycophenolate mofetil peak _{(USP 1-Aug-2023)}

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 the labeled amount of mycophenolate mofetil (C₂₃H₃₁NO₇) in the portion of Tablets taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of mycophenolate mofetil from the Sample solution

r_s = peak response of mycophenolate mofetil from the Standard solution

C_s = concentration of USP Mycophenolate Mofetil RS in the Standard solution (mg/mL)

C_u = nominal concentration of mycophenolate mofetil in the Sample solution (mg/mL)

Acceptance criteria: 94.0%–105.0%

4 PERFORMANCE TESTS

Change to read:

DISSOLUTION (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-um pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857)) _{(USP 1-Aug-2023)}

Mode: UV

Analytical wavelength: 304 nm

Path length: 0.1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of mycophenolate mofetil (C₂₃H₃₁NO₇) dissolved at each time point (i):

Result = (A_u /A_s ) × C_s

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

C_s = concentration of USP Mycophenolate Mofetil RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of mycophenolate mofetil (C₂₃H₃₁NO₇) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = {[C₂ × (V − V_s )] + (C₁ × V_s )} × (1/L) × 100

C_i = concentration of mycophenolate mofetil in the portion of sample withdrawn at the specied time (mg/mL)

V = volume of the Medium, 900 mL

L = label claim (mg/Tablet)

V_s = volume of the Sample solution withdrawn at each time point (mL)

Tolerances: See Table 1.

Table 1

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 ask. Dilute with water to volume.

Buffer: 3.0 mL/L of triethylamine in water. Adjust with Diluted phosphoric acid to a pH of 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 from the Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable lter of 0.45-µm pore size. Transfer 5 mL of the ltrate to a 25mL volumetric ask, and dilute with Diluent to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

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 volume: 20 µL

Run time: NLT 2.5 times the retention time of mycophenolate mofetil peak _{(USP 1-Aug-2023)}

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 concentration (C_i) of mycophenolate mofetil (C₂₃H₃₁NO₇) dissolved at each time point (i):

Result = (r_u /r_s ) × C_s × D

r_u = peak response of mycophenolate mofetil from the Sample solution

r_s = peak response of mycophenolate mofetil from the Standard solution

C_s = concentration of USP Mycophenolate Mofetil RS in the Standard solution (mg/mL)

D = dilution factor of the Sample solution

Calculate the percentage of the labeled amount of mycophenolate mofetil (C₂₃H₃₁NO₇) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = {[C₂ × (V − V_s )] + (C₁ × V_s )} × (1/L) × 100

C_i = concentration of mycophenolate mofetil in the portion of sample withdrawn at the specied time (mg/mL)

V = volume of the Medium, 900 mL

L = label claim (mg/Tablet)

V_s = volume of the Sample solution withdrawn at each time point (mL)

Tolerances: See Table 2.

Table 2

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 lter of 0.45-µm pore size. Dilute 2 mL of the ltrate with

Medium to 100 mL.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.) _{(USP 1-Aug-2023)}

Mode: UV

Analytical wavelength: 250 nm

Path length: 1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of mycophenolate mofetil (C₂₃H₃₁NO₇) dissolved at each time point (i):

Result = (A_u /A_s ) × C_s × D

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

C_s = concentration of USP Mycophenolate Mofetil RS in the Standard solution (mg/mL)

D = dilution factor of the Sample solution, 50

Calculate the percentage of the labeled amount of mycophenolate mofetil (C H NO ) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = {[C₂ × (V − V_s )] + (C₁ × V_s )} × (1/L) × 100

C_i = concentration of mycophenolate mofetil in the portion of sample withdrawn at the specied time (mg/mL)

V = volume of the Medium, 900 mL

L = label claim (mg/Tablet)

V_s = volume of the Sample solution withdrawn at each time point (mL)

Tolerances: See Table 3.

Table 3

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES _{(USP 1-Aug-2023)}

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 from Standard solution _{(USP 1-Aug-2023)} in acetonitrile

System suitability

Samples: Standard solution and Sensitivity solution

Suitability requirements

Tailing factor: NMT 2, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

_{(USP 1-Aug-2023)}

Samples: Standard solution and Sample solution

Calculate the percentage of any specified and unspecified degradation product _{(USP 1-Aug-2023)} in the portion of Tablets taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (1/F) × 100

r_u = peak response of each _{(USP 1-Aug-2023)} impurity from the Sample solution

r_s = peak response of mycophenolate mofetil from the Standard solution

C_s = concentration of USP Mycophenolate Mofetil RS in the Standard solution (mg/mL)

C_u = nominal concentration of mycophenolate mofetil in the Sample solution (mg/mL)

F = relative response factor  _{(USP 1-Aug-2023)} (see Table 4)

Acceptance criteria: See Table 4. The reporting threshold is 0.05%. _{(USP 1-Aug-2023)}

Table 4

^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.

Change to read:

LIMIT OF Z-MYCOPHENOLATE MOFETIL

[NOTE-Z-Mycophenolate mofetil is 2-Morpholinoethyl (Z)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-4-hexenoate. _{(USP 1-Aug-2023)}

Triethylamine solution: Proceed as directed in the Assay.

Mobile phase: Acetonitrile and Triethylamine solution (35:65)

Standard solution: 0.025 mg/mL of USP Mycophenolate Mofetil RS in acetonitrile

Sensitivity solution: 1.25 µg/mL of USP Mycophenolate Mofetil RS from Standard solution _{(USP 1-Aug-2023)} in acetonitrile

Sample solution: Nominally 2.5 mg/mL of mycophenolate mofetil prepared as follows. Transfer Tablets, equivalent to 2.5 g of mycophenolate mofetil, to 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 the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm x 15-cm; 3.5-µm packing 17

Column temperature: 60°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: 1.7 times the retention time of the mycophenolate mofetil peak

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

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of Z-mycophenolate mofetil in the portion of Tablets taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of Z-mycophenolate mofetil from the Sample solution

r_s = peak response of mycophenolate mofetil from the Standard solution

C_s = concentration of USP Mycophenolate Mofetil RS in the Standard solution (mg/mL)

C_u = nominal concentration of mycophenolate mofetil in the Sample solution (mg/mL)

Acceptance criteria: NMT 0.10%

6 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)

USP Mycophenolate Mofetil RS