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Purpose <p>Quetiapine (QUE) is an FDA approved antimanic and antischizophrenic active pharmaceutical ingredient (API). However, quetiapine is disseminated worldwide in tablets requiring special attention regarding its stability on storage. Also, as per the official compendium, a maximum ± 10% of such impure or degradation products is allowed in the API as well in tablets. Hence isolation, explicit characterization and toxicological profiling of such products become pertinent. In addition, recycling opportunity of such products into newer bioactive molecules need to be explored in the realm of drug discovery and circular economy.</p> Methods <p>Acid, base, oxidative, photolytic and thermal degradation pathways are explored first by subjecting QUE to respective conditions. The products were subsequently analyzedby HPLC. Finally, oxidative pathway was chosen for investigation to isolate and characterize the degradation products. Toxicological studies and in vitro antimicrobial activity investigations were undertaken with the obtained degradation products.</p> Results <p>Characterizations revealed, the 3-oxo hydroxyl ethyl chain, two side phenyl rings, the two α-carbon atoms adjacent to piperazine nitrogens and the Sulphur of the central thiazepine ring, have been the most susceptible positions for the oxidation. Different novel degradation products have been obtained from QUE API and QUE tablets. Interestingly, certain degradation products revealed considerable in vitro antimicrobial activity. Mild allergic manifestations were observed afterthe degradation products had been tested on rodents. An overall in silico studies revealed a few adverse effects on human organs.</p> Conclusion <p>Molecules explored from our QUE degradation have been novel till date, providing potential scaffolds for novel antimicrobial agents. The degradation products also insinuated a few adverse effects for drug manufacturers. Above all, this is maiden report on investigations of QUE tablet degradation.</p>

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First Time Exploration of Few Novel Molecules from Oxidative Degradation of Raw and Tableted Quetiapine and Unveiling Their Toxico-Pharmacological Potentials for Future Drug Discovery

  • 期刊论文

  • 发表日期：

    2025年3月27日

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  • Dipanwita Bera,
  • Darakhshan Begum,
  • Balaram Ghosh,
  • Susmita Mallick,
  • Souvik Basak,
  • Nanda Gopal Sahoo

摘要

Purpose

Quetiapine (QUE) is an FDA approved antimanic and antischizophrenic active pharmaceutical ingredient (API). However, quetiapine is disseminated worldwide in tablets requiring special attention regarding its stability on storage. Also, as per the official compendium, a maximum ± 10% of such impure or degradation products is allowed in the API as well in tablets. Hence isolation, explicit characterization and toxicological profiling of such products become pertinent. In addition, recycling opportunity of such products into newer bioactive molecules need to be explored in the realm of drug discovery and circular economy.

Methods

Acid, base, oxidative, photolytic and thermal degradation pathways are explored first by subjecting QUE to respective conditions. The products were subsequently analyzedby HPLC. Finally, oxidative pathway was chosen for investigation to isolate and characterize the degradation products. Toxicological studies and in vitro antimicrobial activity investigations were undertaken with the obtained degradation products.

Results

Characterizations revealed, the 3-oxo hydroxyl ethyl chain, two side phenyl rings, the two α-carbon atoms adjacent to piperazine nitrogens and the Sulphur of the central thiazepine ring, have been the most susceptible positions for the oxidation. Different novel degradation products have been obtained from QUE API and QUE tablets. Interestingly, certain degradation products revealed considerable in vitro antimicrobial activity. Mild allergic manifestations were observed afterthe degradation products had been tested on rodents. An overall in silico studies revealed a few adverse effects on human organs.

Conclusion

Molecules explored from our QUE degradation have been novel till date, providing potential scaffolds for novel antimicrobial agents. The degradation products also insinuated a few adverse effects for drug manufacturers. Above all, this is maiden report on investigations of QUE tablet degradation.