A liquid chromatography configuration providing at least three dimensions of separation coupled with spectrometry greatly improves the ability to detect ions present in samples, including complex biological samples such as blood. Liquid chromatography columns in one embodiment are connected with an in-line trapping column the alternately communicates with the second and third liquid chromatography columns. The liquid chromatography columns are operably connected either to a mass spectrometer (MS) or a nuclear magnetic resonance (NMR) spectrometer. The improved dynamic range of detection allows a method of detecting molecular components present in complex biological samples that serve as biomarkers for a disease state, such as sepsis.