Журнал аналитических и биоаналитических методов

Абстрактный

Development and Validation of a Simple Method for the Detection of Fascaplysin in Plasma

Kenneth H Swartz, Frederick A Valeriote, Joseph Media, Tyler A Johnson, Karen Tenney, Phillip Crews and Jiajiu Shaw

Fascaplysin is a cytotoxic natural product isolated from a variety of Indo-Pacific marine organisms, primarily Fascaplysinopsis sponges and Didemnum tunicates. Positive xenograft studies involving this alkaloid structural class have indicated that fascaplysin may serve as an important lead compound for preclinical development. This study was undertaken as a prelude to a full pharmacokinetics and therapeutic assessment of fascaplysin. We describe here a simple plasma preparation and a rapid HPLC method for the detection of fascaplysin in mice. The method was validated by parameters including good linear correlation, a limit of quantification of 107.1 μg/mL, and a good precision with a coefficient of variation of 0.92% for 10 μg/mL. This method provides excellent sensitivity and visualization of fascaplysin as a single peak allowing for rapid analysis of plasma samples involving absorption, distribution, and metabolism studies. A preliminary pharmacokinetics study in C57Bl/6 mice using 20.6 mg/kg fascaplysin yielded a biphasic curve with T_½α=16.7 min, T_½β=11.7 h, and C₀ of 17.1 μg/mL.