Gadobutrol Impurity

WhatsAPP: +86 17320513646
E-mail: anna@molcoo.com

• Product Information

• Product Number: G021043

• English Name: Gadobutrol Impurity 43

• English Alias: tert-butyl 2,2-dibromoacetate

• CAS Number: 69713-21-9

• Molecular Formula: C6H10Br2O2

• Molecular Weight: 273.95

• Advantages: As a reference standard for Gadobutrol Impurity 43, it features a well-defined chemical structure with high purity (≥98%) and excellent stability under normal storage conditions (2-8℃, protected from light), ensuring batch-to-batch consistency. Its high purity and reliability make it an accurate reference for impurity detection in gadobutrol bulk drugs and formulations, supporting validation of analytical methods such as GC and HPLC, and ensuring the accuracy and standardization of drug quality control.

• Applications:

• Development of Impurity Detection Methods: Used to establish GC-MS or HPLC methods for detecting Impurity 43 in gadobutrol, determining its retention time and linear relationship between peak area and concentration to achieve quantitative analysis of trace impurities (detection limit as low as 0.05%).

• Production Process Monitoring: Monitors the content of Impurity 43 in real time during gadobutrol synthesis (e.g., in halogenation reactions), optimizing reaction conditions (e.g., temperature, brominating agent dosage) to reduce its formation and ensure the bulk drug meets ICH Q3A/B standards.

• Stability Studies: Evaluates the trend of Impurity 43 under accelerated stability tests (e.g., high temperature, high humidity) to provide data for determining drug storage conditions (e.g., sealed storage in a cool place).

• Regulatory Compliance: Meets the impurity limit requirements (usually ≤0.1%) of regulatory agencies such as FDA and EMA, assisting companies in drug registration and approval.

• Background Description: Gadobutrol is a macrocyclic MRI contrast agent used for imaging the central nervous system and abdominal regions. In its synthesis, incomplete control of halogenation reactions (e.g., bromination steps) may introduce bromoacetate impurities (such as Impurity 43). These impurities have potential cytotoxicity and may affect drug safety, making their strict control a critical part of gadobutrol's quality system.

• Research Status:

• Detection Technology: GC-MS  (gas chromatography-mass spectrometry) is primarily used, with separation achieved on an HP-5 capillary column (30m×0.25mm×0.25μm) and detection via electron impact ionization (EI source), enabling qualitative confirmation and quantitative analysis of Impurity 43 with a limit of quantification (LOQ) of 0.02% (S/N≥10).

• Formation Mechanism: Impurity 43 originates from side reactions between brominating reagents (e.g., bromine, hydrobromic acid) and tert-butyl ester intermediates during gadobutrol synthesis. Its yield is positively correlated with the dropping rate of brominating reagents and reaction time. Controlling the reaction temperature below 50℃ and adopting dropwise addition of brominating reagents can reduce Impurity 43 content to below 0.08%.

• Safety Evaluation: Toxicological studies show that the median lethal dose (LD50) of Impurity 43 in rats is 200mg/kg, suggesting a regulatory limit of ≤0.1% in drug standards. In recent years, some companies have controlled its content below 0.03% through improved purification processes (e.g., column chromatography).

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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