Mass balance in rapamycin autoxidation

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

来源：Journal of Pharmaceutical and Biomedical Analysis, 2008, 48(5): 1368-1374.

DOI：10.1016/j.jpba.2008.09.030

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

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.

• 出版日期2008-12-15