Product Information：
Product Number: B075024
English Name: Belumosudil Impurity 24
English Alias: 3-(carboxymethoxy)benzoic acid
CAS Number: 1878-61-1
Molecular Formula: C₉H₈O₅
Molecular Weight: 196.16
Advantages：
High-purity standard：HPLC purity ≥99.0%, with structure confirmed by 1H NMR, 13C NMR, and HRMS, meeting the quality requirements of FDA and EMA for impurity reference standards, enabling precise qualitative and quantitative analysis.
Good stability：Stable for 24 months when stored at -20°C in the dark, with a degradation rate <1% after 7 days at room temperature in solution (e.g., methanol-water system), suitable for long-term quality monitoring and stability studies.
Clear process characteristics：As a characteristic impurity from carboxymethylation or hydrolysis side reactions in belumosudil hydrochloride synthesis, it accurately tracks process risks of excessive sodium chloroacetate or ester bond hydrolysis during phenolic hydroxyl carboxymethylation.
Applications：
Pharmaceutical quality control：Used for LC-MS/MS detection of Impurity 24 in belumosudil hydrochloride APIs and formulations, controlling its content ≤0.1% in accordance with ICH Q3A standards to ensure compliance with quality requirements for Rho kinase inhibitor drugs.
Synthesis process optimization：In carboxymethylation or hydrolysis reactions, monitoring impurity content (e.g., adjusting sodium chloroacetate dosage or reaction pH to reduce impurity from 0.8% to 0.1%) optimizes reaction conditions to minimize by-product formation.
Analytical method development：Serves as a phenolic acid impurity reference standard for establishing specific detection methods, such as ultra-performance liquid chromatography-ultraviolet detection (UPLC-UV), achieving accurate quantification using characteristic absorption of carboxylic acid groups (λ=230nm) (limit of quantitation LOQ=0.05μg/mL).
Toxicological research support：Provides samples for evaluating the potential toxicity of phenolic acid impurities, facilitating in vitro cytotoxicity tests and in vivo genotoxicity studies to meet regulatory requirements for impurity safety assessment.
Background Description：
During belumosudil hydrochloride synthesis, improper control of phenolic hydroxyl carboxymethylation reactions (such as excessive sodium chloroacetate or high reaction temperature) or intermediate ester bond hydrolysis under acidic conditions may generate 3-(carboxymethoxy)benzoic acid (Impurity 24). The impurity’s dicarboxylic acid structure may affect drug water solubility and metabolic pathways. According to ICH Q3A/B guidelines, strict limit control of such process-related impurities is required to ensure drug safety and efficacy.
Research Status：
Advances in detection technology：UPLC-MS/MS is employed using a C18 column (1.7μm, 2.1×100mm) with 0.1% formic acid aqueous solution-acetonitrile (gradient elution) as the mobile phase, achieving a detection limit (LOD) of 0.01ppm for precise analysis of trace phenolic acid impurities.
Formation mechanism research：This impurity mainly originates from excessive reagents in the nucleophilic substitution reaction of phenolic hydroxyl groups with sodium chloroacetate or ester bond hydrolysis during acidic workup. Using catalytic amounts of sodium carbonate and controlling the reaction temperature below 40℃ can reduce impurity formation by over 80%.
Safety evaluation：In vitro Ames tests showed no mutagenicity at concentrations ≤200μg/dish, but renal tubular damage was observed in high-dose groups (100mg/kg) during a 28-day repeated dosing test in rats. Based on toxicological data, a recommended limit of ≤0.08% is proposed.
WhatsAPP: +86 17320513646
E-mail: anna@molcoo.com
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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