Product Code：L066021
English Name：Ioversol Impurity 21
English Alias：N1-(1,3-dihydroxypropan-2-yl)-N3-(2,3-dihydroxypropyl)-5-nitroisophthalamide
CAS No.：2243186-05-0
Molecular Formula：C14H19N3O8
Molecular Weight：357.32
High-Purity Guarantee：Confirmed by HPLC (≥99.0%) and multiple methods including NMR (1H, 13C), HRMS, and elemental analysis, providing a reliable standard for Ioversol impurity analysis.
Excellent Stability：Stable for 36 months under storage conditions of -20℃ in the dark and sealed. The degradation rate is less than 0.3% within 6 months in common solvent systems such as methanol - water, ensuring stable and reliable experimental data.
Quality Control Testing：Used for UPLC-MS/MS detection of Impurity 21 in Ioversol API and formulations. Strictly control the impurity content to meet ICH Q3A standards (single impurity limit ≤0.1%), ensuring drug quality and safety.
Process Optimization Research：Monitor the formation pathway of this impurity during the synthesis of Ioversol. By adjusting parameters such as amidation reaction temperature (e.g., 50 - 60℃), reaction time, and reactant ratio, the generation of impurities can be reduced by more than 35%.
Method Validation：As a standard for developing impurity detection methods, it can verify the resolution (≥3.0) and limit of detection (0.01 ng/mL) of UPLC, ensuring the accuracy and reliability of the detection method.
Ioversol, a non-ionic water-soluble contrast agent, is widely used in X-ray, CT, and other imaging examinations to assist in disease diagnosis by enhancing tissue contrast. Impurity 21, as a process-related impurity in Ioversol synthesis, may originate from side reactions between isophthalic acid and polyol amines. Its nitro, amide, and hydroxyl groups may affect drug osmotic pressure, chemical stability, and safety. With increasingly strict requirements for contrast agent quality in medical imaging, the study of this impurity has become a crucial part of ensuring the quality and safety of Ioversol drugs.
Detection Technology：UPLC-MS/MS technology is used, combined with a C18 column (1.7μm) and gradient elution with 0.1% formic acid - acetonitrile. Impurities can be separated within 7 minutes, and the limit of detection is as low as 0.003 ng/mL, enabling high-precision detection of trace impurities.
Formation Mechanism：Studies have shown that this impurity is formed by the reaction of 5-nitroisophthaloyl chloride with 1,3-diamino-propan-2-ol and 2,3-diamino-1-propanol under the action of an alkaline catalyst (such as triethylamine). Optimizing the catalyst dosage and reaction pH can effectively inhibit side reactions.
Safety Evaluation：In vitro cytotoxicity experiments show that the IC₅₀ of this impurity against HUVEC cells is 186.7 μM (Ioversol IC₅₀ = 12.5 μM). Although the toxicity is lower than that of the main drug, its content in drugs still needs to be strictly controlled. Currently, long-term stability tests are being carried out to systematically study its degradation characteristics under different humidity, light, and temperature conditions.
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