Zonisamide Capsules

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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1 DEFINITION

Zonisamide Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of zonisamide (C₈H₈N₂O₃S).

2 IDENTIFICATION

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

Change to read:

B. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

Sample solution: Shake the contents of a sufficient quantity of Capsules, equivalent to about 100 mg of zonisamide, with 5 mL of methanol. Sonicate for 2 min and pass through a filter of 0.45-µm pore size or equivalent. Discard the initial 1-mL portion and evaporate the solution at 85°. Cool the residue. Use 1-2 mg of the residue.

Analysis: The IR spectrum of the Sample solution corresponds to the IR spectrum of similarly prepared USP Zonisamide RS.

3 ASSAY

3.1 PROCEDURE

Mobile phase: Acetonitrile, methanol, and 0.1% trifluoroacetic acid TS (20:16:64)

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: Nominally 1.0 mg/mL of zonisamide prepared as follows. Transfer a suitable amount of Capsule contents (NLT 10) to a suitable volumetric flask and add a suitable volume of methanol. Sonicate and shake for 15 min. Dilute with methanol to volume. Alternatively, the Sample stock solution can be prepared as follows. Transfer a suitable amount of Capsules (NLT 10) in a suitable volumetric flask, add 20% of the flask 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

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 237 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1.0 mL/min

Injection volume: 10 µL

Run time: 1.5 times the retention time of the zonisamide

3.3 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zonisamide (C₈H₈N₂O₃S) in the portion of Capsules taken:

Result = (r_U/r_S) x (C_S/C_U) x 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 = nominal concentration of zonisamide in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

Change to read:

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Medium: Water; 900 mL

Apparatus 2: 75 rpm. Use suitable sinkers, if necessary. (ERR 1-May-2018)

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

Sample solution: 10 mL of the solution under test. Dilute the filtrate with Medium as given in Table 2.

Table 2

Instrumental conditions

Mode: UV

Analytical wavelength: 241 nm

Cell: 1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of zonisamide (C₈H₈N₂O₃S) dissolved:

Result = (A_U/A_S) x (C_S/L) x V x 100

A_U = absorbance from the Sample solution

A_S = absorbance from the Standard solution

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

L = label claim (mg/Capsule)

V = volume of Medium, 900 mL

Chromatographic procedure

Solution A: 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 Solution A (25:5:70)

Standard stock solution: 0.4 mg/mL of USP Zonisamide RS prepared as follows. Transfer a suitable amount of USP Zonisamide RS to a suitable volumetric flask, and dissolve in 20% of the flask volume of acetonitrile. Dilute with Medium to volume.

Standard solution: (L/1000) mg/mL of USP Zonisamide RS in Medium, where L is the label claim in mg/Capsule from Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 238 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Flow rate: 1.0 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 3.0%

Calculate the percentage of the labeled amount of zonisamide (C₈H₈N₂O₃S) dissolved:

Result = Result = (r_U/r_S) x (C_S/L) x V x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = 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 zonisamide (C₈H₈N₂O₃S) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Solution A: 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 Solution A (25:5:70)

Standard stock solution: 0.32 mg/mL of USP Zonisamide RS. Transfer a suitable amount of USP Zonisamide RS in a suitable volumetric flask, dissolve in 20% of flask volume of acetonitrile and 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. Transfer a suitable amount of USP Zonisamide Related Compound C RS to a suitable volumetric flask, and dissolve in 20% flask volume of methanol. Dilute with Mobile phase to volume.

System suitability solution: Equal volumes of Standard stock solution and System suitability stock solution

Sample stock solution: Transfer a suitable number of Capsules (NLT 10) to a suitable volumetric flask, dissolve in 20% flask volume of water and dilute with Mobile phase to volume to obtain a solution of concentration as given in Table 3. [NOTE-Stir and warm slightly for 30 min to dissolve the Capsules.]

Table 3

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 x 25-cm; 5-µm packing L1

Flow rate: 1.0 mL/min

Injection volume: 20 µL

Run time: 6 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 degradation product in the portion of Capsules taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of each degradation product from the Sample solution

r_S = peak response of zonisamide from the Standard solution s

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

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

Acceptance criteria: See Table 4. Disregard any peak below 0.1%.

Table 4

^a Process impurity included in the table for identification and system suitability only. Process impurities are controlled in the drug substance and are not to be reported or included in the total degradation products for the drug product.

^b 1-Benzisoxazol-3-yl-N-methylmethanesulfonamide.

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

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight containers and protected from light. Store at controlled room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Zonisamide RS

USP Zonisamide Related Compound C RS

N'-(Benzisoxazol-3-ylmethylsulfonyl)-N,N-dimethylformimidamide.

C₁₁H₁₃N₃O₃S 267.30