How to improve the sensitivity in detecting lowest concentration (LOD, LLOQ) of analyte in plasma by HPLC method? I am using fluorescence detector for my analysis and the concentration is in the range of nanogram. I want to go to lowest concentration (2.5 ng) but am worried about peaks of endogenous compounds of plasma (though not interfering in the retention time of my analytes). The detector only responded upto 10 ng. Please suggest the methods to go to less than these concentration. I am using liquid-liquid extraction for my method development.