title: Mass balance in rapamycin autoxidation.
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.
authors.affiliation: University of Minnesota Duluth, Duluth, MN 55812, USA. aoyler@d.umn.edu
authors.forename: Alan R
authors.initials: AR
authors.lastname: Oyler
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Armstrong
authors.forename: Richard
authors.initials: R
authors.lastname: Dunphy
authors.forename: Lori
authors.initials: L
authors.lastname: Alquier
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Maryanoff
authors.forename: Judith H
authors.initials: JH
authors.lastname: Cohen
authors.forename: Mel
authors.initials: M
authors.lastname: Merciadez
authors.forename: Ada
authors.initials: A
authors.lastname: Khublall
authors.forename: Rajshekhar
authors.initials: R
authors.lastname: Mehta
authors.forename: Ashesh
authors.initials: A
authors.lastname: Patel
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Il'ichev
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D019281:Dimerization; D054855:Drug-Eluting Stents; D007166:Immunosuppressive Agents / Q000032:analysis / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D012031:Refractometry / Q000379:methods; D020123:Sirolimus / Q000032:analysis / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus