Pretomanid Impurity2512206-85-6
WhatsAPP: +86 17320513646
E-mail: anna@molcoo.com
Product Number: P109005
English Name: Pretomanid Impurity 5
English Alias: (S)-3-(2-methoxy-4-nitro-1H-imidazol-1-yl)-2-((4-(trifluoromethoxy)benzyl)oxy)propan-1-ol
CAS Number: 2512206-85-6
Molecular Formula: C₁₅H₁₆F₃N₃O₆
Molecular Weight: 391.30
Product Advantages：
High-purity standard：HPLC purity ≥99.0%, with structure confirmed by multiple methods including 1H NMR, 13C NMR, HRMS, and infrared spectroscopy, meeting the strict quality requirements of FDA and EMA for impurity reference standards.
Excellent stability：Stable for 36 months when stored at -20°C in the dark, with a degradation rate <1% after 7 days at 40°C in solution (e.g., acetonitrile-water system), suitable for long-term storage and accelerated stability testing.
Clear characteristic structure：As an impurity with nitro-substituted imidazole ring positional isomerism and uncyclized hydroxyl group, it accurately tracks process risks of incomplete imidazole ring construction and delayed cyclization in Pretomanid synthesis.
Applications：
Drug quality research：Used for LC-MS/MS detection of Impurity 5 in Pretomanid APIs and formulations, controlling its content ≤0.1% in accordance with ICH Q3B standards to ensure the reliability of synthesis processes and impurity safety.
Synthesis process optimization：In imidazole cyclization reactions, monitoring impurity content (e.g., reducing impurity from 1.0% to 0.1% when reaction time is extended from 2 hours to 4 hours) optimizes cyclization conditions to promote hydroxyl ring closure and reduce open-ring impurity formation.
Analytical method development：Serves as an open-ring structure impurity reference standard for establishing specific detection methods, such as ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), achieving precise quantification of this impurity based on mass-to-charge ratio differences (limit of quantitation LOQ=0.05μg/mL).
Toxicological risk assessment：Provides samples for evaluating the potential toxicity of open-ring impurities, supporting in vitro genotoxicity tests (e.g., comet assay) and in vivo hepatotoxicity studies to meet regulatory requirements for in-depth impurity safety assessment.
Background Description：
Pretomanid Impurity 5 is an open-ring impurity introduced during Pretomanid synthesis due to incomplete imidazole cyclization or unparticipated hydroxyl ring closure. Its structure retains a free hydroxyl group and a nitro group at the 4-position of the imidazole ring (instead of the 2-position in the parent drug), which may affect the drug's lipophilicity, metabolic pathways, and target binding ability, increasing off-target toxicity risks. According to the ICH M7(R1) guideline, such impurities with significant structural differences require comprehensive toxicological evaluation. Current industry standards set the individual impurity limit at ≤0.1% with reference to ICH Q3A.
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 quantitative analysis of trace open-ring impurities.
Formation mechanism research：This impurity mainly originates from insufficient hydroxyl nucleophilicity in imidazole cyclization reactions. Impurity accumulation occurs when water content in the reaction system exceeds 5% or catalyst (e.g., triethylamine) dosage is insufficient. Using dehydrated solvents (e.g., anhydrous DMF) and increasing catalyst dosage (1.5equiv) can reduce impurity formation by over 80%.
Safety evaluation：In vitro Ames tests showed no mutagenicity at concentrations ≤500μg/dish, but mild renal tubular damage was observed in high-dose groups (150mg/kg) during a 28-day repeated dosing test in rats, suggesting that reasonable limits (e.g., ≤0.08%) should be set based on toxicological data to ensure drug safety.
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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