Lamotrigine Tablets
711
Test 3:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
DEFINITION
Lamotrigine Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of lamotrigine (C9H7Cl2N5).
IDENTIFICATION
• A. Ultraviolet Absorption 197U
197U
Standard solution:
0.02 mg/mL of USP Lamotrigine RS in 0.01 N hydrochloric acid
Sample solution:
0.02 mg/mL of lamotrigine from crushed powdered Tablets in 0.01 N hydrochloric acid
Acceptance criteria:
The spectra of the Standard solution and Sample solution exhibit maxima and minima at the same wavelengths.
• B.
The retention time of the lamotrigine peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
Change to read:
• Procedure
Buffer:
0.8 g/L of ammonium acetate. Adjust with glacial acetic acid to a pH of 4.5.
Mobile phase:
Methanol and Buffer (60:40)
Standard solution:
0.05 mg/mL of USP Lamotrigine RS in Mobile phase
Sample solution:
Transfer an amount equivalent to 100 mg of lamotrigine from a portion of crushed Tablets (NLT 20)(RB 1-May-2011) to a suitable volumetric flask to obtain a nominal concentration of lamotrigine of 1.0 mg/mL. Dissolve in 70% of the flask volume of Mobile phase by sonicating for 20 min. Dilute with Mobile phase to volume. Centrifuge the solution. Quantitatively dilute a suitable volume of centrifugate with Mobile phase to obtain a nominal concentration of 0.05 mg/mL of lamotrigine.
an amount equivalent to 100 mg of lamotrigine from a portion of crushed Tablets (NLT 20)(RB 1-May-2011) to a suitable volumetric flask to obtain a nominal concentration of lamotrigine of 1.0 mg/mL. Dissolve in 70% of the flask volume of Mobile phase by sonicating for 20 min. Dilute with Mobile phase to volume. Centrifuge the solution. Quantitatively dilute a suitable volume of centrifugate with Mobile phase to obtain a nominal concentration of 0.05 mg/mL of lamotrigine.
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
1 mL/min
Injection size:
10 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0 for lamotrigine
Relative standard deviation:
NMT 2.0% for lamotrigine
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of lamotrigine (C9H7Cl2N5) 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 Lamotrigine RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of lamotrigine in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
Change to read:
• Dissolution 711
Test 1
Medium:
0.1 N hydrochloric acid; 900 mL
Apparatus 2:
50 rpm
Time:
30 min
Determine the amount of lamotrigine (C9H7Cl2N5) dissolved by using one of the following methods.
Spectrometric method
Standard stock solution:
0.15 mg/mL of USP Lamotrigine RS in Medium prepared as follows. Dissolve a suitable quantity in 5% of the flask volume of methanol, then dilute with Medium to volume.
Standard solution:
Dilute the Standard stock solution with Medium to obtain a final concentration of 0.028 µg/mL.USP35
Dilute the Standard stock solution with Medium to obtain a final concentration of 0.028 µg/mL.USP35
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Dilute with Medium according to Table 1.
USP35
according to Table 1.
Table 1
| Tablet Label Claim (mg) |
Volume of Sample (mL) |
Volume of Volumetric Flask |
Final Concentration (mg/mL) |
|---|---|---|---|
| 25 | — | — | 0.028 |
| 100 | 5.0 | 20 | 0.029 |
| 150 | 4.0 | 25 | 0.027 |
| 200 | 3.0 | 25 | 0.027 |
USP35
Instrumental conditions
Mode:
UV
Analytical wavelength:
267 nm
Blank:
Medium
Analysis
Calculate the percentage of the labeled amount of lamotrigine (C9H7Cl2N5) dissolved:
Result = (AU/AS) × (CS/L) × D ×USP35V × 100
D ×USP35V × 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) |
| D | = | = dilution factor of the Sample solutionUSP35 |
| V | = | = volume of Medium, 900 mL |
Chromatographic method
Buffer and Mobile phase:
Prepare as directed in the Assay.
Standard stock solution:
0.5 mg/mL of USP Lamotrigine RS in Medium, prepared as follows. Dissolve a suitable quantity in 15% of the flask volume of methanol, then dilute with Medium to volume.
Standard solution:
(L/1000) mg/mL of USP Lamotrigine RS from the Standard stock solution in Medium, where L is the label claim in mg/Tablet
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Column:
4.6-mm × 15-cm; 5-µm packing L1
Detector:
UV 310 nm
Flow rate:
1 mL/min
Injection size:
See Table 2.
Table 2
| Label Claim (mg/Tablet) |
Injection Size (µL) |
|---|---|
| 25 | 50 |
| 100, 150, 200 | 10 |
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0 for lamotrigine
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of lamotrigine (C9H7Cl2N5) dissolved:
Result = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of lamotrigine is dissolved.
Test 2:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium, Apparatus, and Time:
Proceed as directed for Test 1.
Analysis:
Determine the amount of lamotrigine dissolved using either the Spectrometric method or Chromatographic method described in Test 1.
Tolerances:
NLT 75% (Q) of the labeled amount of lamotrigine is dissolved.
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
Time:
15 min
Standard solution:
(L/900) mg/mL of USP Lamotrigine RS in Medium, where L is the Tablet label claim in mg
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Instrumental conditions
Mode:
UV
Analytical wavelength:
270 nm
Cell
For Tablets labeled to contain 100, 150, or 200 mg:
0.2-cm flow cell
For Tablets labeled to contain 25 mg:
1 cm
Blank:
Medium
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of lamotrigine (C9H7Cl2N5) 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 |
Tolerances:
NLT 80% (Q) of the labeled amount of lamotrigine is dissolved.(RB 1-May-2011)
(RB 1-May-2011)
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Change to read:
• Organic Impurities
Buffer:
Prepare as directed in the Assay.
Mobile phase:
Acetonitrile, methanol, and Buffer (10:30:60)
Diluent:
Methanol and Buffer (60:40)
System suitability solution:
1 µg/mL of Lamotrigine Related Compound B RS and 0.4 mg/mL of USP Lamotrigine RS in Diluent
Standard solution:
1.0 µg/mL of USP Lamotrigine RS in Diluent
Sample solution:
Transfer an amount equivalent to 100 mg of lamotrigine from a portion of crushed Tablets (NLT 20)(RB 1-May-2011) to a suitable volumetric flask to obtain a nominal concentration of lamotrigine of about 0.4 mg/mL. Dissolve in 70% of the flask volume of Mobile phase by sonicating and shaking intermittently for 30 min. Dilute with Diluent to volume. Pass through a membrane filter of 0.45-µm pore size.
an amount equivalent to 100 mg of lamotrigine from a portion of crushed Tablets (NLT 20)(RB 1-May-2011) to a suitable volumetric flask to obtain a nominal concentration of lamotrigine of about 0.4 mg/mL. Dissolve in 70% of the flask volume of Mobile phase by sonicating and shaking intermittently for 30 min. Dilute with Diluent to volume. Pass through a membrane filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Flow rate:
1 mL/min
Injection size:
5 µL
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 2.0 between lamotrigine related compound B and lamotrigine, System suitability solution
Tailing factor:
NMT 2.0 for lamotrigine, Standard solution
Relative standard deviation:
NMT 10.0% for lamotrigine, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of any individual 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 lamotrigine from the Standard solution |
| CS | = | = concentration of USP Lamotrigine RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of lamotrigine in the Sample solution (mg/mL) |
| F | = | = relative response factor for the corresponding impurity (see Table 3) |
Acceptance criteria:
See Table 3.
Table 3
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Lamotrigine related compound Ba | 0.67 | 0.75 | 0.2 |
| Lamotrigine | 1.0 | — | — |
| Lamotrigine related compound Cb | 1.5 | 1.0 | 0.5 |
| Any individual unspecified degradation impurity | — | 1.0 | 0.2 |
| Total impurities | — | — | 0.75 |
|
a
2,3-Dichlorobenzoic acid.
b
3-Amino-6-(2,3-dichlorophenyl)-1,2,4-triazin-5(4H)-one.
|
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ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed 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 Lamotrigine RS
USP Lamotrigine Related Compound B RS
2,3-Dichlorobenzoic acid.
C7H4Cl2O2 191.01
2,3-Dichlorobenzoic acid.
C7H4Cl2O2 191.01
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Hariram Ramanathan, M.S.
Associate Scientific Liaison 1-301-816-8313 |
(SM42010) Monographs - Small Molecules 4 |
| 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 3637
Pharmacopeial Forum: Volume No. 36(6) Page 1542