Product Number: P059052
English Name: Pomalidomide Impurity 52
English Alias: 2-((2,6-dioxopiperidin-3-yl)carbamoyl)benzoic acid
CAS Number: 6139-18-0
Molecular Formula: C₁₃H₁₂N₂O₅
Molecular Weight: 276.24
As an impurity reference standard for pomalidomide, this compound has the following advantages:
Well-defined structure and high stability, enabling analysis of side reaction mechanisms during pomalidomide synthesis, such as piperidinedione ring and benzoyl group linkage, to optimize processes and reduce amide impurity generation;
As a bicyclic reference standard containing piperidinedione and benzoyl groups, it provides a standard substance for detecting polycyclic impurities in drugs, improving the quantitative accuracy of methods like HPLC and LC-MS;
Helps study the impact of piperidinedione structures on drug stability and toxicological properties (piperidinediones may participate in in vivo amide bond hydrolysis reactions) to provide a scientific basis for impurity control strategies.
Drug Development: Used as an impurity reference standard to identify and quantify Impurity 52 in pomalidomide preparations, evaluating the purity of APIs and formulations;
Quality Control: Acting as a standard substance to validate the sensitivity and specificity of detection methods (e.g., HPLC, LC-MS), ensuring the impurity content meets pharmacopoeia and regulatory requirements during production;
Stability Studies: Investigating the degradation behavior of this impurity under light, high temperature, and high humidity conditions to evaluate its impact on pomalidomide formulation stability, assisting in determining storage conditions.
Pomalidomide is a derivative of thalidomide, clinically used for treating multiple myeloma. During its synthesis, if carbamoylation reaction conditions are out of control or intermediate product condensation is abnormal, impurities containing piperidinedione structures such as 2-((2,6-dioxopiperidin-3-yl)carbamoyl)benzoic acid are easily generated. Since such impurities may affect drug bioavailability or produce toxic metabolites, research on them is a key part of pomalidomide quality control.
Current research focuses on:
Detection Method Optimization: Establishing trace detection methods (detection limits reach ppb level) for this impurity using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology to enhance impurity separation in complex matrices;
Synthesis Process Improvement: Reducing by-product generation by optimizing the construction conditions (such as reaction temperature, solvent polarity) of piperidinedione rings, and developing high-purity impurity synthesis routes;
Toxicological Evaluation: Studying the potential mutagenicity of piperidinedione structures through in vitro Ames tests and animal models to provide data support for establishing safe limits;
Crystallization Behavior Research: Analyzing the cocrystallization characteristics of this impurity with pomalidomide to evaluate its impact on drug formulation crystal form stability and improve the quality control system.
China
