Identification of Degradation Product of Deguelin and Its Stability Using Liquid Chromatography and Electrospray/Mass Spectrometry

Abstract

The degradation product and its stability of deguelin, a naturally occurring rotenoid and potential cancer chemopreventive agent, was evaluated in several vehicles using liquid chromatography‐electrospray mass spectrometry. Deguelin was prepared as a 2 mg/mL solution in acetonitrile, corn oil, yohimbine oil, Tween‐80, Cremophor‐EL, liposomes, and phospholipid micelles, and chemical stability was monitored for 28 days using HPLC‐UV and HPLC‐MS systems coupled to C₁₈ reverse phase columns. Deguelin was stable in acetonitrile, corn oil, and yohimbine oil for 28 days when stored at 4°C. However, it rapidly decomposed in liposomes, Cremophor‐EL, Tween 80, and phospholipid micelles, with daily decay rates of 0.39%, 0.86%, 1.93%, and 2.82%, respectively. The degradation product was determined by physical and spectral data to be tephrosin after isolation by semi‐preparative HPLC. Tephrosin was produced by deguelin auto‐oxidation, and this was likely accelerated by endogenous peroxides found in Cremophor‐EL, Tween‐80, and phospholipid preparations.

Keywords:

• Degradation
• Deguelin
• Stability
• Tephrosin
• LC‐MS

Acknowledgment

This work was supported by National Cancer Institute grants P01 CA48112 and U01/U19 CA52956.