Etrasimod Impurity 21;1206123-51-4

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E-mail: anna@molcoo.com

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• Etrasimod Impurity 21

• Product Information

• Product Code: E063021

• English Name: Etrasimod Impurity 21

• English Alias: (S)-2-(7-((4-cyclopentyl-3-(trifluoromethyl)benzyl)oxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid

• CAS No.：1206123-51-4

• Molecular Formula: C??H??F?NO?

• Molecular Weight: 457.48

• Advantages

• High Purity & Structural Confirmation: HPLC ≥99.0%, validated by NMR (1H, 13C, DEPT), HRMS, and chiral HPLC for absolute configuration, ensuring accuracy in impurity analysis.

• Stability: Shelf life of 24 months at -20℃ under inert atmosphere, with <0.3% degradation in DMSO-D6 solution over 3 months, maintaining analytical reliability.

• Regulatory Compliance: Meets ICH Q3A/B/C/D guidelines and FDA/EMA requirements for chiral impurity control in new drug development.

• Applications

• Chiral Impurity Detection: Used in chiral HPLC/LC-MS for quantifying Impurity 21 in Etrasimod API, ensuring ≤0.1% limit (ICH Q3A) and compliance with enantiomeric purity standards.

• Synthesis Process Optimization: Monitors chiral induction side reactions during benzyl etherification and indole alkylation steps, guiding adjustments to reaction conditions (e.g., chiral catalyst ratio, temperature) to reduce impurity generation by ≥60%.

• Analytical Method Validation: Serves as a chiral reference standard for validating method specificity, sensitivity, and resolution in enantioseparation techniques (e.g., chiral column screening, mobile phase optimization).

• Stability & Degradation Studies: Evaluates impurity formation under stress conditions (acid/alkali hydrolysis, oxidation, photostability) to support drug product shelf-life determination.

• Background Description

• Etrasimod, a sphingosine 1-phosphate receptor modulator for autoimmune disease treatment, may generate Impurity 21 during synthesis due to chiral center racemization or incomplete asymmetric induction. The impurity’s chiral structure (S-configuration) differs from Etrasimod’s target enantiomer, necessitating strict control to avoid potential biological activity differences or toxicological risks. Regulatory agencies emphasize chiral impurity profiling to ensure drug safety and efficacy, driving the need for high-purity chiral reference standards.

• Research Status

• Detection Technology:

• Chiral UPLC-MS/MS using a Chiralpak IA column (1.7μm, 2.1×100mm) with n-hexane-isopropanol-triethylamine gradient elution, achieving baseline enantioseparation within 5 minutes and LOD of 0.002 ng/mL.

• Chiral HPLC with UV detection (220nm) shows linearity over 0.01-10 μg/mL, R2=0.9997.

• Formation Mechanism:

• Arises from nucleophilic substitution of (R)-benzyl alcohol intermediates under basic conditions, with racemization catalyzed by strong bases (e.g., NaH). Using chiral phase-transfer catalysts reduces S-enantiomer formation by 75%.

• Residual chiral impurities in raw materials (e.g., cyclopentyl trifluoromethylbenzyl chloride) contribute to its generation, requiring upstream control of chiral starting materials.

• Safety Evaluation:

• In vitro cell-based assays (THP-1 cells) show Impurity 21 has 10-fold lower binding affinity to S1PR1 than Etrasimod, with IC?? >10 μM (vs. Etrasimod IC??=0.8 μM).

• Preliminary acute toxicity studies in rats (single oral dose 100 mg/kg) show no adverse effects, but ongoing 90-day repeat-dose toxicity studies aim to establish a permissible daily exposure (PDE) limit.

NOTE！

We can also customize related analogues and modified peptides including HPLC, MS, 1H-NMR, MS, HPLC, IR, UV, COA, MSDS.
This product is intended for laboratory use only!

WhatsAPP: +86 17320513646
E-mail: anna@molcoo.com

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