Product Number: C046002A
English Name: Chlorphenamine Impurity C
English Alias: 3-(4-chlorophenyl)-N-methyl-3-(pyridin-2-yl)propan-1-amine
CAS Number: None
Molecular Formula: C₁₅H₁₇ClN₂
Molecular Weight: 260.76
As Impurity C of Chlorphenamine, this compound has the following advantages:
Well-defined with distinct functional groups: Contains 3-(4-chlorophenyl)-3-(pyridin-2-yl)propane skeleton and N-methylamine structure. Unlike chlorphenamine (antihistamine with N,N-dimethyl tertiary amine), its secondary amine polarity, chlorine electronegativity, and pyridine aromaticity create significant differences, enabling precise differentiation via HPLC/ion-exchange chromatography as a specific marker;
High stability and traceability: Rigid benzene/pyridine rings and stability of C-N bonds ensure neutral-condition stability. As a byproduct from incomplete methylation in synthesis or demethylation in metabolism, it directly reflects methylation efficiency or metabolic pathways, improving process and metabolic tracing accuracy;
High detection sensitivity: Benzene-pyridine conjugation shows strong UV absorption (250-280nm), combined with m/z 261 [M+H]⁺ enabling ppb-level analysis via LC-MS, compatible with antihistamine amine impurity systems.
Pharmaceutical quality control: Used as an impurity reference standard to quantify Chlorphenamine Impurity C in APIs, ensuring residual monomethylated byproducts meet quality standards;
Synthesis optimization: Optimizing methylation conditions (reagent dosage) by monitoring impurity levels to enhance N,N-dimethylation specificity and reduce monomethyl byproducts;
Metabolism studies: Analyzing in vivo metabolic pathways of chlorphenamine to confirm if demethylation is a major route, supporting drug disposition and safety assessment.
Chlorphenamine contains an N,N-dimethyl tertiary amine group, synthesized via amine methylation. Incomplete methylation (e.g., insufficient methylating agent) may generate monomethyl secondary amine derivatives like Chlorphenamine Impurity C. Additionally, chlorphenamine may undergo N-demethylation via CYP450 enzymes in vivo to form this impurity. Due to amine substitution differences affecting lipophilicity and antihistaminic activity, its residues impact chlorphenamine quality and efficacy, requiring strict control.
Current research focuses on:
Analytical method validation: Developing HPLC assays with C18 columns for separation, achieving 0.1 ppb detection limits;
Methylation kinetics: Studying impurity formation under varying methylating agent concentrations to clarify mono-to-dimethylation pathways;
Control strategies: Optimizing methylation parameters (excess reagent) to keep impurity levels below 0.1% and enhance API purity;
Structural confirmation: Using ¹H/¹³C-NMR and mass spectrometry to verify secondary amine structure, distinguishing from chlorphenamine for authoritative identification
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