Zonisamide Capsules
DEFINITION
Zonisamide Capsules contain NLT 90.0% and NMT 110.0% of zonisamide (C8H8N2O3S), based on label claim.
IDENTIFICATION
• 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
Mobile phase:
Acetonitrile, methanol, and 0.1% trifluoroacetic acid (5:4:16)
Standard stock solution:
1 mg/mL of USP Zonisamide RS in methanol
Standard solution:
0.1 mg/mL of zonisamide in Mobile phase, from the Standard stock solution
Sample stock solution:
1 mg/mL of zonisamide in methanol from the contents of NLT 10 Capsules with Capsule shell. [Note—Sonicate, and shake for 15 min. ]
Alternately, the Sample stock solution can be prepared as follows:
Place NLT 10 Capsules in a suitable volumetric flask. Fill 20% of the final volume with water. Stir, and warm slightly for 30 min. Dilute with Mobile phase to volume.
Sample solution:
0.1 mg/mL of zonisamide in Mobile phase, from the Sample stock solution
Chromatographic system
Mode:
LC
Detector:
UV 237 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Column temperature:
30
Flow rate:
1.0 mL/min
Injection size:
10 µL
Run time:
1.5 times the retention time of the zonisamide peak
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 percentage of zonisamide (C8H8N2O3S) in the portion of Capsules 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 | = | = nominal concentration of zonisamide in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Medium:
Water; 900 mL
+'&img=../../images/v35300/m89996-f1-pf346.gif&casNumber=&usp=35&nf=30&chemicalStructureImage=false&ID='+parent.myID,600,500);)
Time:
45 min
Determine the percentage of zonisamide dissolved using one of the following procedures.
Spectrophotometric procedure
Standard stock solution:
0.6 mg/mL of USP Zonisamide RS in methanol
Standard solution:
Dilute the Standard stock solution with Medium to obtain solutions with final concentrations as given in Table 1.
Table 1
| Capsule Strength (mg) |
Final Concentration (µg/mL) |
|---|---|
| 25 | 13 |
| 50 | 13 |
| 100 | 22 |
Sample solution:
10 mL of the solution under test. Dilute the filtrate with Medium as given in Table 2.
Table 2
| Capsule Strength (mg) |
Volume of Filtrate (mL) |
Final Volume (mL) |
|---|---|---|
| 25 | 5.0 | 10.0 |
| 50 | 5.0 | 25.0 |
| 100 | 5.0 | 25.0 |
Detector:
UV
Analytical wavelength:
241 nm
Cell:
1 cm
Blank:
Medium
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of zonisamide dissolved:
Result = (AU/AS) × (CS/L) × V × 100
| AU | = | = absorbance from the Sample solution |
| AS | = | = absorbance from the Standard solution |
| CS | = | = concentration of USP Zonisamide RS in the Standard solution (mg/mL) |
| L | = | = label claim (mg/Capsule) |
| V | = | = volume of Medium, 900 mL |
Chromatographic procedure
Buffer:
Dilute 52 mL of 40% tetrabutylammonium hydroxide solution with 948 mL of water. Adjust with phosphoric acid to a pH of 7.5.
Mobile phase:
Acetonitrile, methanol, and Buffer (5:1:14)
Standard stock solution:
0.4 mg/mL of USP Zonisamide RS prepared as follows:
Dissolve USP Zonisamide RS first in acetonitrile, using 20% of final volume. Dilute with Medium to volume.
Standard solution:
Dilute the Standard stock solution with Medium to obtain a final concentration of about L/1000 mg/mL, where L is the label claim in mg/Capsule.
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 238 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Flow rate:
1.0 mL/min
Injection size:
10 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 1.5
Relative standard deviation:
NMT 3.0%
Calculate the percentage of zonisamide 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 Zonisamide RS in the Standard solution (mg/mL) |
| L | = | = label claim (mg/Capsule) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 70% (Q) of the labeled amount of C8H8N2O3S is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Buffer:
Dilute 52 mL of 40% tetrabutylammonium hydroxide solution with 948 mL of water. Adjust with phosphoric acid to a pH of 7.5.
Mobile phase:
Acetonitrile, methanol, and Buffer (5:1:14)
Standard stock solution:
0.32 mg/mL of USP Zonisamide RS. Dissolve first in acetonitrile using 20% of the final volume, and then dilute with Mobile phase to volume.
Standard solution:
0.32 µg/mL of zonisamide in Mobile phase, from the Standard stock solution
System suitability stock solution:
0.4 mg/mL of zonisamide related compound C. Dissolve USP Zonisamide Related Compound C RS first in methanol using 20% of the final volume, and then dilute with Mobile phase to volume.
System suitability solution:
Equal volumes of Standard stock solution and System suitability stock solution
Sample stock solution:
Dissolve a suitable number of Capsules (NLT 10) first in water using 20% of the final volume, and then dilute with Mobile phase to volume to obtain a solution with a concentration as given in Table 3. [Note—Stir and warm slightly for 30 min to dissolve the Capsules. ]
Table 3
| Capsule Strength (mg) |
Final Concentration (mg/mL) |
|---|---|
| 25 | 2 |
| 50 | 2 |
| 100 | 4 |
Sample solution:
0.32 mg/mL of zonisamide in Mobile phase, from the Sample stock solution
Chromatographic system
Mode:
LC
Detector:
UV 238 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Flow rate:
1.0 mL/min
Injection size:
20 µL
Run time:
Six times the retention time of the zonisamide peak
System suitability
Samples:
Standard solution and System suitability solution
Suitability requirements
Resolution:
NLT 2.0 between zonisamide and zonisamide related compound C, System suitability solution
Tailing factor:
NMT 1.5 for the zonisamide peak, System suitability solution
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 Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of each individual 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 | = | = nominal concentration of zonisamide in the Sample solution (mg/mL) |
Acceptance criteria
[Note—Disregard any peak below 0.1%. ]
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 0.5%
Impurity Table 1
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|---|---|---|
| Zonisamide | 1.0 | — |
| Zonisamide related compound Ca* | 1.3 | — |
| Methyl zonisamideb | 1.6 | 0.2 |
| Zonisamide related compound Ac | 2.5 | 0.2 |
| Any individual unspecified impurity |
— | 0.2 |
|
a
N'-(Benzisoxazol-3-ylmethylsulfonyl)-N,N-dimethylformimidamide.
b
1-Benzisoxazol-3-yl-N-methylmethanesulfonamide.
c
1,2-Benzisoxazole-3-methane sulfonic acid.
*
For identification and system suitability purposes.
|
||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers and protected from light. Store at controlled room temperature.
• USP Reference Standards 11
11
USP Zonisamide RS 
') + '&img=../../images/v35300/cas-68291-97-4.gif',600,500);)
USP Zonisamide Related Compound C RS
N'-(Benzisoxazol-3-ylmethylsulfonyl)-N,N-dimethylformimidamide.
C11H13N3O3S 267.30
N'-(Benzisoxazol-3-ylmethylsulfonyl)-N,N-dimethylformimidamide.
C11H13N3O3S 267.30
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 5087
Pharmacopeial Forum: Volume No. 36(2) Page 436