Sensitivity enhancement in LC-ESI-MS method using mobile phase additives to quantify Simalikalactone E

A quassinoid, Simalikalactone E (SkE), extracted from Quassia amara L. (Simaroubaceae) leaves in our laboratory, displayed strong in vitro and in vivo antimalarial activities and also a very promising effect against chronic myeloid leukemia. In order to optimize the SkE purification process form the plant (present at very low concentration) and further pharmacokinetic studies in biological fluids, a robust and sensitive quantification method was needed. We present here the development of a LC-MS method using single ion monitoring to response the requirement of quantification of SkE. The effects of mobile phase additives using sodium, lithium and ammonium adducts formation were investigated. The ESI in the positive ion mode with aqueous mobile phase containing 0.25 nM of sodium acetate was proved to be the most efficient to improve the sensitivity of the detection. The calibration curve was linear over the concentration range of 0.896 and 8.96 ppm with R2>0.998. The limits of detection and quantification were12.3 ppb and 38.1 ppb respectively. The intra-day precision and accuracy were less than 3.39% and 7%, respectively, while the inter-day precision and accuracy were less than 3.55% and 7.75%, respectively. We will finally present the application of this method for the quantification of SkE in all steps of the purification process.