Mass balance in rapamycin autoxidation

Alan R. Oyler, Barbara L. Armstrong, Richard Dunphy, Lori Alquier, Cynthia A. Maryanoff, Judith H. Cohen, Mel Merciadez, Ada Khublall, Rajshekhar Mehta, Ashesh Patel, Yuri V. Il'ichev

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The immunosuppressant drug rapamycin is a complex polyene-containing natural product which undergoes autoxidation. The resulting product mixtures contained numerous monomeric and oligomeric compounds, which represented challenges for addressing mass balance in forced degradation studies and in analysis of aged developmental drug-eluting stents. A combination of SEC with ultraviolet and refractive index detection and RP-HPLC was used to account for drug loss and product formation. The mass balance methodology was subsequently validated for the determination of rapamycin and composite rapamycin autoxidation product material in developmental stent samples. This mass balance approach may find general applicability in other situations where drugs degrade to a plethora of products, which cannot be determined individually and summed.

Original languageEnglish (US)
Pages (from-to)1368-1374
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume48
Issue number5
DOIs
StatePublished - Dec 15 2008

Keywords

  • Autoxidation
  • Mass balance
  • RP-HPLC
  • Rapamycin
  • SEC

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