Zonisamide
C8H8N2O3S 212.23
1,2-Benzisoxazole-3-methanesulfonamide
[68291-97-4].
(zoe nis' a mide).
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C8H8N2O3S 212.23
1,2-Benzisoxazole-3-methanesulfonamide
[68291-97-4].DEFINITION
Zonisamide contains NLT 98.0% and NMT 102.0% of C8H8N2O3S, calculated on the anhydrous basis.
IDENTIFICATION
• 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:
1.36 g/L of monobasic potassium phosphate in water. Adjust the pH to 3.0 ± 0.1 with 10% phosphoric acid.
Mobile phase:
Acetonitrile, methanol, and Buffer (1:1:8)
Standard solution:
0.1 mg/mL of USP Zonisamide RS in Mobile phase
Sample solution:
0.1 mg/mL of Zonisamide in Mobile phase
Chromatographic system
Mode:
LC
Detector:
UV 240 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 5000 theoretical plates
Tailing:
NMT 1.8
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C8H8N2O3S in the portion of Zonisamide taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of zonisamide from the Sample solution |
| rS | = | = peak response of zonisamide from the Standard solution |
| CS | = | = concentration of USP Zonisamide RS in the Standard solution (mg/mL) |
| CU | = | = concentration of Zonisamide in the Sample solution (mg/mL) |
Acceptance criteria:
98.0%–102.0% on the anhydrous basis
IMPURITIES
Organic Impurities
• Procedure
Mobile phase:
Prepare as directed in the Assay.
Standard solution:
1 µg/mL of USP Zonisamide RS and 1.5 µg/mL of USP Zonisamide Related Compound A RS in Mobile phase
Sample solution:
1.0 mg/mL of Zonisamide in Mobile phase
Chromatographic system:
Prepare as directed in the Assay.
Run time:
2 times the retention time of the zonisamide peak
System suitability
Sample:
Standard solution
Suitability requirements
Resolution:
NLT 10.0 between zonisamide related compound A and zonisamide
Relative standard deviation:
NMT 10.0% for both zonisamide and zonisamide related compound A peaks
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of zonisamide related compound A in the portion of Zonisamide taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response of zonisamide related compound A from the Sample solution |
| rS | = | = peak response of zonisamide related compound A from the Standard solution |
| CS | = | = concentration of USP Zonisamide Related Compound A RS in the Standard solution (mg/mL) |
| CU | = | = concentration of zonisamide related compound A in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of zonisamide related compound A (free acid), 213.23 |
| Mr2 | = | = molecular weight of USP Zonisamide Related Compound A RS (sodium salt), 235.23 |
Calculate the percentage of any unspecified impurity in the portion of Zonisamide taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of zonisamide from the Standard solution |
| CS | = | = concentration of USP Zonisamide RS in the Standard solution (mg/mL) |
| CU | = | = concentration of Zonisamide in the Sample solution (mg/mL) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 0.3%
Impurity Table 1
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|
|---|---|---|---|
| Zonisamide related compound Aa | 0.51 | 0.15 | |
| Zonisamide | 1.0 | — | |
| Any unspecified individual impurity | — | 0.10 | |
|
a
1,2-Benzisoxazole-3-methane sulfonic acid.
|
|||
SPECIFIC TESTS
• Water Determination, Method I 
921
:
NMT 0.8%
921:
NMT 0.8%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers, and store at room temperature.
• USP Reference Standards 11
11
USP Zonisamide RS 
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USP Zonisamide Related Compound A RS
1,2-Benzisoxazole-3-methanesulfonic acid sodium salt.
C8H6NNaO4S 235.19[CAS-73101-64-1].
1,2-Benzisoxazole-3-methanesulfonic acid sodium salt.
C8H6NNaO4S 235.19
[CAS-73101-64-1].
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 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 5086
Pharmacopeial Forum: Volume No. 34(6) Page 1489