Rizatriptan EP Impurity A

Details:

Rizatriptan EP Impurity A(Dihydrochloride)

Product Information

• Product Code：R047002A

• English Name：Rizatriptan EP Impurity A(Dihydrochloride)

• English Alias：2-(5-((1H-1,2,4-triazol-1-yl)methyl)-2-((3-(2-(dimethylamino)ethyl)-1H-indol-5-yl)methyl)-1H-indol-3-yl)-N,N-dimethylethanamine dihydrochloride

• CAS No.：[Not Available]

• Molecular Formula：CHN·2HCl

• Molecular Weight：542.54

Advantages

• High-Purity Reference Standard：Confirmed by HPLC (≥99.0%), NMR (1H, 13C), HRMS, and elemental analysis, compliant with EP (European Pharmacopoeia) impurity standards for Rizatriptan quality control.

• Stability Assurance：Stable for 36 months at -20℃ under light-protected, sealed storage; degradation rate <0.3% in aqueous solution (pH 4-6) within 6 months.

Applications

• Quality Control Testing：Used for HPLC and LC-MS detection of EP Impurity A in Rizatriptan API and formulations, controlling content to meet EP standards (≤0.1%).

• Process Optimization Research：Monitors impurity formation during Rizatriptan synthesis, reducing generation by >50% by adjusting condensation temperature (e.g., 80-90℃) and reaction time.

• Method Validation：Serves as an EP standard for developing impurity detection methods, verifying HPLC resolution (≥2.5) and LOD (0.01 ng/mL).

Background Description

Rizatriptan, a 5-HT receptor agonist, is used for migraine treatment. Impurity A, specified by EP, may originate from alkylation side reactions of the indole ring or triazole group introduction during synthesis. Its polyamino and indole ring system may affect drug stability and efficacy. With stricter EMA enforcement of EP standards, studying such officially designated impurities is crucial for drug registration and manufacturing.

Research Status

• Detection Technology：UPLC-MS/MS with C18 column (1.7μm) and 0.1% formic acid-acetonitrile gradient elution achieves separation within 4 minutes, with LOD of 0.003 ng/mL for EP-compliant trace analysis.

• Formation Mechanism：Formed by reaction of 3-(2-(dimethylamino)ethyl)-5-methylindole with 1,2,4-triazolylmethyl halide under alkaline conditions (e.g., potassium carbonate catalysis); optimizing catalyst dosage and solvent polarity (e.g., DMF-water system) inhibits side reactions.

• Safety Evaluation：In vitro cytotoxicity shows IC of 186.5 μM against SH-SY5Y cells (Rizatriptan IC=12.3 μM), with low toxicity but requiring ≤0.1% limit. Long-term stability testing is ongoing to monitor degradation under different pH conditions.