Mass balance in rapamycin autoxidation.
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.
Oyler
Alan R
AR
University of Minnesota Duluth, Duluth, MN 55812, USA. aoyler@d.umn.edu
Armstrong
Barbara L
BL
Dunphy
Richard
R
Alquier
Lori
L
Maryanoff
Cynthia A
CA
Cohen
Judith H
JH
Merciadez
Mel
M
Khublall
Ada
A
Mehta
Rajshekhar
R
Patel
Ashesh
A
Il'ichev
Yuri V
YV
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
D007166:Immunosuppressive Agents; D020123:Sirolimus