Topiramate Tablets
DEFINITION
Topiramate Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of topiramate (C12H21NO8S).
IDENTIFICATION
• A. Infrared Absorption 
197F
197F
Wavenumber range:
4000–650 cm
1
1
Standard solution:
20 mg/mL of USP Topiramate RS in acetone
Sample solution:
Grind an appropriate number of Tablets to prepare a 20-mg/mL topiramate solution in acetone. Shake the solution for 30 min, and centrifuge for 10 min. Then pass an aliquot of the clear supernatant through a suitable nylon filter of 0.45-µm pore size, and use the filtrate for analysis.
Analysis:
Apply 50 µL of the Standard solution to a sodium chloride plate, allow the solution to dry, and then obtain the IR spectrum. Wash the window with acetone, and repeat the same procedure using the Sample solution.
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Buffer:
1.54 g/L of ammonium acetate in water. Adjust with glacial acetic acid to a pH of 4.0.
Diluent:
Methanol and water (1:4)
Mobile phase:
Methanol and Buffer (1:4)
Standard solution:
6 mg/mL of USP Topiramate RS in Diluent
Sample solution:
6 mg/mL of topiramate in Diluent from NLT 12 Tablets, based on the label claim. [Note—Shake vigorously for at least 30 min, and pass a portion through a chemical-resistant filter (PTFE) of 0.45-µm pore size. ]
Chromatographic system
Mode:
LC
Detector:
Refractive index
Column:
4.6-mm × 25-cm; 5-µm packing L1
Temperature
Column:
35
Detector:
35
Flow rate:
1.5 mL/min
Injection size:
100 µL
System suitability
Sample:
Standard solution
Suitability requirements
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of topiramate (C12H21NO8S) 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 Topiramate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of topiramate in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
711
Test 1
Medium:
Water; 900 mL
Apparatus 2:
50 rpm
Time:
20 min
Mobile phase:
0.1% trifluoroacetic acid in water and methanol (1:1)
Standard solution:
0.1 mg/mL of USP Topiramate RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable filter of 1-µm pore size.
Chromatographic system
Mode:
LC
Detector:
Refractive index
Guard column:
4.0-mm × 1-cm
Column:
4.6-mm × 25-cm; 5-µm packing L11
Temperature
Column:
40
Detector:
40
Flow rate:
1.2 mL/min
Injection size:
100 µL
System suitability
Sample:
Standard solution
Suitability requirements
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of topiramate (C12H21NO8S) 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 USP Topiramate RS in 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 topiramate is dissolved.
Test 2:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium:
Water; 900 mL, deaerated
Apparatus 2:
50 rpm
Time:
40 min
Standard solution:
(L/900) mg/mL of USP Topiramate RS 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, discarding the first few mL.
Mobile phase:
Water and acetonitrile (1:1)
Chromatographic system
Mode:
LC
Detector:
Refractive index
Column:
4.6-mm × 25-cm; 5-µm packing L1
Temperature
Column:
30
Detector:
50
Flow rate:
1.0 mL/min
Injection size:
100 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Column efficiency:
NLT 5000 theoretical plates
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of topiramate (C12H21NO8S) 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 USP Topiramate RS in 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 topiramate is dissolved.
Test 3:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Medium:
Water; 900 mL
Apparatus 2:
50 rpm
Time:
30 min
Diluent:
Acetonitrile and water (1:1)
Mobile phase:
Water and acetonitrile (55:45)
Standard solution:
1.1 mg/mL of USP Topiramate RS in Diluent. Dilute with Medium to obtain a final concentration of about (L/900) mg/mL, where L is the label claim in mg/Tablet.
Sample solution:
Pass a portion of the solution under test through a suitable filter, discarding the first few mL.
Chromatographic system
Mode:
LC
Detector:
Refractive index
Column:
4.6-mm × 25-cm; 5-µm packing L1
Temperature
Column:
50
Detector:
50
Flow rate:
1.2 mL/min
Injection size:
100 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 2000 theoretical plates
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of topiramate (C12H21NO8S) 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 USP Topiramate RS in 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 topiramate is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
• Related Compounds
Diluent, Mobile phase, Sample solution, and Chromatographic system:
Proceed as directed in the Assay.
Standard solution:
1.2 mg/mL of USP Topiramate RS and 0.6 mg/mL of USP Topiramate Related Compound A RS in Diluent
Peak identification solution:
0.6 mg/mL each of USP Topiramate RS and USP Topiramate Related Compound A RS in Diluent
System suitability
Samples:
Standard solution and Peak identification solution
[Note—Identify the peaks due to topiramate related compound A and topiramate using the relative retention times given in Table 1. ]
Suitability requirements
Relative standard deviation:
NMT 5.0%, Standard solution
Analysis
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 for the individual impurity from the Sample solution |
| rS | = | = peak response of topiramate from the Standard solution |
| CS | = | = concentration of USP Topiramate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of topiramate in the Sample solution (mg/mL) |
| F | = | = relative response factor (see Table 1) |
Acceptance criteria
See Table 1.
Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Topiramate related compound A | 0.66 | 1.1 | 0.5 |
| Topiramate | 1.0 | — | — |
| Individual unspecified degradation product | — | — | 0.2 |
| Total impurities | — | — | 0.7 |
SPECIFIC TESTS
• Limit of Sulfamate and Sulfate
[Note—Use water with resistivity NLT 18 megohm-cm for preparation of the Mobile phase, Standard solution, and Sample solution. ]
Buffer:
0.8 g/L of p-hydroxybenzoic acid in water
Mobile phase:
Methanol and Buffer (2.5:97.5). Adjust with sodium hydroxide solution to a pH of 9.4 ± 0.5.
Standard solution:
0.015 mg/mL each of sodium sulfate and sulfamic acid in Mobile phase from anhydrous sodium sulfate and sulfamic acid, respectively
Sample solution:
Transfer a suitable amount of ground powder from NLT 20 Tablets to a suitable volumetric flask to obtain a nominal concentration of 6 mg/mL of topiramate. Add 80% of the flask volume of Mobile phase, and shake for 30 min. Sonicate for 10 min, and dilute with Mobile phase to volume. Centrifuge, and pass through a polyethersulfone membrane filter of 0.45-µm pore size, discarding the first 3 mL of the filtrate.
Chromatographic system
Mode:
LC
Detector:
Conductivity
Column:
4.6-mm × 15-cm; 5-µm packing L47
Detector temperature:
30
Flow rate:
1.5 mL/min
[Note—A suitable background suppression unit may be used. ]
Injection size:
70 µL
System suitability
Sample:
Standard solution
[Note—The approximate relative retention time of the sulfamate ion peak is 0.44 relative to the sulfate ion peak. ]
Suitability requirements
Relative standard deviation:
NMT 15.0% for the sulfamate and sulfate peaks
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of sulfate ion in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response of sulfate ion from the Sample solution |
| rS | = | = peak response of sulfate ion from the Standard solution |
| CS | = | = concentration of sodium sulfate in the Standard solution (mg/mL) |
| CU | = | = concentration of topiramate in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of the sulfate anion, 96.04 |
| Mr2 | = | = molecular weight of anhydrous sodium sulfate, 142.04 |
Calculate the percentage of sulfamate ion in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response of sulfamate ion from the Sample solution |
| rS | = | = peak response of sulfamate ion from the Standard solution |
| CS | = | = concentration of sulfamic acid in the Standard solution (mg/mL) |
| CU | = | = concentration of topiramate in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of the sulfamate anion, 96.09 |
| Mr2 | = | = molecular weight of sulfamic acid, 97.09 |
Acceptance criteria:
NMT 0.25% of sulfate ion; NMT 0.25% of sulfamate ion
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Store in tightly closed containers at controlled room temperature, protected from moisture.
• 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 Topiramate RS 
2,3:4,5-Di-O-isopropylidene-
-d-fructopyranose sulfamate.
C12H21NO8S 339.36
') + '&img=../../images/v35300/cas-97240-79-4.gif',600,500);)
2,3:4,5-Di-O-isopropylidene-
-d-fructopyranose sulfamate.
C12H21NO8S 339.36
USP Topiramate Related Compound A RS
2,3:4,5-Bis-O-(1-methylethylidene)--d-fructopyranose.
C12H20O6 260.28
') + '&img=../../images/v35300/c11rs2140.gif',600,500);)
2,3:4,5-Bis-O-(1-methylethylidene)-
-d-fructopyranose.
C12H20O6 260.28
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 4900
Pharmacopeial Forum: Volume No. 34(5) Page 1197