Lamotrigine Tablets
DEFINITION
Lamotrigine Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of lamotrigine (C9H7Cl2N5).
IDENTIFICATION
•  A. Ultraviolet Absorption 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.
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
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.
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
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)
•  Uniformity of Dosage Units 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.
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.
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
USP Lamotrigine RS
USP Lamotrigine Related Compound B RS
2,3-Dichlorobenzoic acid.
    C7H4Cl2O2        191.01
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USP35–NF30 Page 3637
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