A simple and reliable method for determining plasma concentration of dehydroxymethylepoxyquinomicin by high performance liquid chromatography with mass spectrometry

We have developed a simple and reliable method for determining plasma concentration of dehydroxymethylepoxyquinomicin (DHMEQ), a new low molecular weight NF-kappa B inhibitor, using high performance liquid chromatography with mass spectrometry (LC-MS). An experiment of mass spectrometry with electrospray ionization in the negative ionization mode was performed to detect ion transitions at m/z 260.05 [M-H](-) for DHMEQ and 240.29 for mefenamic acid as an internal standard. The samples were purified using liquid-liquid extraction with ethyl acetate. The method yielded a standard curve which was linear for the concentration range of 0.1-125 ng/mL when 0.05 mL plasma was used. The correlation coefficients of all standard curves were greater than or equal to 0.999. The limit of detection was 50 pg/mL (signal/noise >3). Daily fluctuation of plasma standard curve was small. The intra- and inter-assay precision ranged from 2.84 to 4.76% (n = 6) and 2.91 to 7.03% (n = 6), respectively. The LC-MS technique described provides a simple and reliable liquid chromatographic method for the determination of DHMEQ level and for use in studies involving pharmacokinetics. (C) 2008 Elsevier B.V. All rights reserved.