Keywords

• 4447-64-7
• Bempedoic Acid Impurity
• Bempedoic Acid

Quick Details

• ProName: ethyl 2,2,4-trimethyl-3-oxopentanoate
• CasNo: 4447-64-7
• Molecular Formula: C10H18O3
• Appearance: White solid
• Application: Pharmaceutical research
• DeliveryTime: prompt delivery
• PackAge: Screw bottle,foil bags,Reagent bottles
• Port: shenzhen/hongkong
• ProductionCapacity: 5000 Metric Ton/Year
• Purity: 95%+
• Storage: cool and dry
• Transportation: DHL,FedEx,UPS,EMS,TNT;
• LimitNum: 1 Kilogram
• Moisture Content: 0.1%
• Impurity: 0.1%

Superiority

Advantages：

• High-purity standard：HPLC purity ≥99.0%, with structure confirmed by 1H NMR, 13C NMR, and HRMS, meeting the quality requirements of international regulatory agencies such as FDA and EMA for impurity reference standards, enabling precise qualitative and quantitative analysis.

• Excellent stability：Stable for 36 months when stored at -20°C in the dark, with a degradation rate <1% after 14 days at room temperature in solution (e.g., methanol-water system), suitable for long-term quality monitoring and accelerated stability testing.

• Clear process relevance：As a characteristic impurity from hydroxylation reactions or de-esterification side reactions in bempedoic acid synthesis, it directly tracks process risks of incomplete condensation or ester bond hydrolysis.

Details

Product Information：
Product Number: B079022
English Name: Bempedoic Acid Impurity 22
English Alias: ethyl 2,2,4-trimethyl-3-oxopentanoate
CAS Number: 4447-64-7
Molecular Formula: CHO
Molecular Weight: 186.25

Applications：

• Pharmaceutical quality control：Used for LC-MS/MS detection of Impurity 21 in bempedoic acid APIs and formulations, controlling its content ≤0.1% in accordance with ICH Q3A standards to ensure compliance with impurity limits for lipid-regulating drugs.

• Synthesis process optimization：During bempedoic acid synthesis, monitoring impurity content (e.g., adjusting hydroxylation reaction pH or extending reaction time to reduce impurity from 0.9% to 0.1%) optimizes reaction conditions to minimize by-product formation.

• Analytical method development：Serves as a reference standard for establishing specific detection methods, such as ultra-performance liquid chromatography-ultraviolet detection (UPLC-UV), achieving accurate quantification using characteristic UV absorption (λ=210nm) (limit of quantitation LOQ=0.05μg/mL).

• Toxicological risk assessment：Provides samples for evaluating the potential toxicity of hydroxycarboxylic acid impurities, supporting in vitro cytotoxicity tests and in vivo hepatotoxicity studies to meet ICH M7(R1) requirements for genotoxic impurity assessment.

Background Description：
Bempedoic Acid is a novel ATP citrate lyase inhibitor that lowers LDL-C levels by inhibiting cholesterol synthesis. Impurity 21 (6-hydroxy-2,2-dimethylhexanoic acid) is an intermediate residue or de-esterification impurity potentially generated during synthesis, which may affect drug purity and safety. According to the ICH Q3A guideline, such process-related impurities require strict limit control, and their content directly reflects the stability and controllability of the synthesis process.

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 under multiple reaction monitoring (MRM) mode, suitable for trace impurity analysis.

• Formation mechanism research：This impurity mainly originates from insufficient oxidant in hydroxylation reactions or ester bond hydrolysis under acidic conditions. Optimizing the reaction system (e.g., using excess hydrogen peroxide or adjusting reaction pH to neutral) can reduce impurity formation by over 85%.

• Safety evaluation：In vitro tests show the impurity has an IC >2000μg/mL against HepG2 cells, indicating low toxicity. However, mild renal tubular damage was observed in high-dose groups (200mg/kg) during a 28-day repeated dosing test in rats, suggesting a recommended limit of ≤0.08% based on toxicological data.