N-Methyl Zonisamide NEW

Product Code: Z010003

English Name: N-Methyl Zonisamide

English Alias: 1-(benzo[d]isoxazol-3-yl)-N-methylmethanesulfonamide

CAS Number: 68292-02-4

Molecular Formula: C₉H₁₀N₂O₃S

Molecular Weight: 226.25

High-Purity Reference Standard: With ≥99.0% purity (HPLC normalization), its structure is confirmed by 1H/13C NMR and ESI-MS, meeting the requirements of pharmacopoeias such as USP and EP for impurity references.

Strong Stability: Stored at 2-8°C in the dark, it has a shelf life of 24 months, with <1% degradation in solution (e.g., acetonitrile) at room temperature for 7 days, suitable for long-term quality monitoring.

Precise Impurity Tracking: As an N-methylated byproduct of zonisamide, it specifically traces the residual risk of methylation reagents (e.g., methyl iodide) in synthesis, assisting process optimization.

Impurity Quantitative Analysis: Used for HPLC detection of N-Methyl Zonisamide in zonisamide API and formulations, controlling its content ≤0.3% (refer to ICH Q3A standards).

Process Optimization Validation: In methylation reactions, monitoring this impurity's content (e.g., reducing from 0.7% to 0.1% at a 1:1.1 raw material ratio) optimizes methylation reagent dosage to reduce byproduct formation.

Stability Studies: Evaluates the impurity's growth trend in formulations under accelerated stability tests (60°C/RH75%), providing data for packaging material selection (e.g., aluminum foil light-protected packaging).

Regulatory Compliance Support: Helps enterprises meet FDA, EMA, and other requirements for genotoxic impurity (GTI) screening, especially for process routes involving methylation steps.

Detection Technology: HPLC-UV uses a C18 column (4.6×250mm, 5μm) with acetonitrile-0.1% phosphoric acid solution (40:60, v/v) as the mobile phase, detecting at 225nm with a LOQ of 0.05%. LC-MS/MS further lowers the detection limit to 0.01ppm for trace screening.

Formation Mechanism: Mainly originates from excessive reaction of methylation reagents (e.g., methyl iodide, dimethyl sulfate) with intermediates, with significantly increased production at temperatures >50°C or reagent excess >1.5x. Controlled low-temperature (<=30°C) dropwise addition of methylation reagents at a molar ratio of 1:1.05 effectively inhibits impurity formation.

Safety Evaluation: Rat toxicology tests show no obvious toxicity at doses ≤100mg/kg, but long-term exposure may cause mild renal tubular damage, indicating the need for strict limits in drug standards (e.g., ≤0.15%).