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Degradation kinetics and mechanism of RH1, a new anti-tumor agent: A technical note

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Summary and Conclusions

The degradation of RH1 in aqueous solution is found to be both acid and base catalyzed. The maximum stability is obtained in neutral pH but still degrades by 10% (t90) after just 1 week. The stability profile at pH 5 was done, and 4 major degradation products were observed in acid solutions. LC-MS was performed and the molecular weights determined, from which a degradation mechanism was proposed. Degradation products I, II, and III form 2 isomers each depending on which aziridine group is hydrolyzed. No significant effect of light or the presence of antioxidants was observed, indicating that photodegradation and oxidation are not likely degradation reactions.

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Authors and Affiliations

  1. Wyeth Research, 10965, Pearl River, NY

    Neera Jain

  2. Cydex Inc, 66214, Lenexa, KS

    Stephen G. Machatha

  3. Pharmaceutical Resources Branch, National Cancer Institute, NIH, 20892, Bethesda, MD

    S. Esmail Tabibi

  4. Department of Pharmacy Practice and Science, College of Pharmacy, The University of Arizona, 85721, Tucson, AZ

    Samuel H. Yalkowsky

Authors
  1. Neera Jain
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  2. Stephen G. Machatha
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  3. S. Esmail Tabibi
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  4. Samuel H. Yalkowsky
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Corresponding author

Correspondence to Stephen G. Machatha.

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Published: March 2, 2007

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Jain, N., Machatha, S.G., Tabibi, S.E. et al. Degradation kinetics and mechanism of RH1, a new anti-tumor agent: A technical note. AAPS PharmSciTech 8, 16 (2007). https://doi.org/10.1208/pt0801016

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  • DOI: https://doi.org/10.1208/pt0801016

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