Product Number: B007041A
English Name: Brexpiprazole Impurity 41(Dihydrochloride)
English Alias: 4-(piperazin-1-yl)benzo[b]thiophene 1-oxide dihydrochloride
CAS Number: None
Molecular Formula: C₁₂H₁₄N₂OS.2HCl
Molecular Weight: 234.32 (free base); 2×36.46 (dihydrochloride moiety)
As an impurity of Brexpiprazole (in dihydrochloride form), this compound has the following advantages:
Well-defined with distinct functional groups: Contains benzo[b]thiophene 1-oxide ring, 4-piperazinyl, and dihydrochloride groups. Unlike brexpiprazole (antipsychotic with unoxidized thiophene), its sulfoxide (-S=O) polarity, piperazine basicity, and hydrochloride hydrophilicity create significant differences, enabling precise differentiation via HPLC/ion-exchange chromatography as a specific marker;
High stability and water solubility: The dihydrochloride form significantly enhances water solubility (compared to free base), and the rigid structure ensures stability under acidic conditions, suitable for long-term storage as a solution standard;
High detection sensitivity: Benzothiophene oxide conjugation shows strong UV absorption (240-270nm), combined with m/z 235 [M+H]⁺ (free base) enabling ppb-level analysis via LC-MS, compatible with antipsychotic oxidation impurity systems.
Pharmaceutical quality control: Used as an impurity reference standard to quantify Brexpiprazole Impurity 41(Dihydrochloride) in APIs, ensuring residual thiophene oxidation byproducts meet quality standards;
Synthesis optimization: Optimizing oxidation conditions (oxidant selectivity) by monitoring impurity levels to reduce over-oxidation and enhance target stability;
Degradation pathway analysis: Identifying thiophene oxidation as a key degradation route to guide storage improvements (e.g., light protection).
Brexpiprazole contains a benzo[b]thiophene ring, which may undergo oxidation (e.g., by oxidants/air) during synthesis or storage, forming 1-oxide derivatives like 4-(piperazin-1-yl)benzo[b]thiophene 1-oxide, often as dihydrochloride for stability. With altered thiophene oxidation state affecting lipophilicity, its residues impact brexpiprazole quality and safety, making control critical for assurance.
Current research focuses on:
Analytical method validation: Developing UPLC assays with C18 columns for separation, achieving 0.05 ppb detection limits;
Oxidation mechanisms: Studying impurity formation kinetics under varying oxidant concentrations to clarify thiophene oxidation pathways;
Control strategies: Using antioxidants (e.g., vitamin C) to keep impurity levels below 0.1% and enhance API purity;
Structural confirmation: Using ¹H/¹³C/³³S-NMR to verify sulfoxide oxidation state, distinguishing from brexpiprazole for authoritative identification.
China
