Zonisamide

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₈H₈N₂O₃S 212.23

1,2-Benzisoxazole-3-methanesulfonamide CAS RN®: 68291-97-4; UNII: 459384H98V.

1 DEFINITION

Zonisamide contains NLT 98.0% and NMT 102.0% of C₈H₈N₂O₃S, calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (ERR 1-Oct-2020)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 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

(See Chromatography 〈621〉, System Suitability.)

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 = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of zonisamide from the Sample solution

r_S = peak response of zonisamide from the Standard solution

C_S = concentration of USP Zonisamide RS in the Standard solution (mg/mL)

C_U = concentration of Zonisamide in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

Inorganic Impurities

Residue on Ignition 〈281〉: NMT 0.1%

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 = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response of zonisamide related compound A from the Sample solution

r_S = peak response of zonisamide related compound A from the Standard solution

C_S = concentration of USP Zonisamide Related Compound A RS in the Standard solution (mg/mL)

C_U = concentration of zonisamide in the Sample solution (mg/mL)

M_r1 = molecular weight of zonisamide related compound A (free acid), 213.23

M_r2 = 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 = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of zonisamide from the Standard solution

C_S = concentration of USP Zonisamide RS in the Standard solution (mg/mL)

C_U = 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

^a 1,2-Benzisoxazole-3-methane sulfonic acid.

5 SPECIFIC TESTS

Water Determination, Method I 〈921〉: NMT 0.8%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and store at room temperature.

USP Reference Standards 〈11〉

USP Zonisamide RS

USP Zonisamide Related Compound A RS

1,2-Benzisoxazole-3-methanesulfonic acid sodium salt.

C₈H₆NNaO₄S 235.19 CAS RN®: CAS-73101-64-1.