Bridging the polar and hydrophobic metabolome in single-run untargeted liquid chromatography-mass spectrometry dried blood spot metabolomics for clinical purposes
2021
Dried blood spot (DBS) metabolite analysis is a central tool for the clinic, e.g. newborn screening. Instead of applying multiple analytical methods, a single liquid chromatography-mass spectrometry (LC-MS) method was developed for metabolites spanning from highly polar glucose to hydrophobic long-chain acylcarnitines. For liquid chromatography, a diphenyl column and a multi-linear solvent gradient operated at elevated flow rates allowed for an even-spread resolution of diverse metabolites. Injecting moderate volumes of DBS organic extracts directly, in contrast to evaporation and reconstitution, provided substantial increases in analyte recovery. Q Exactive MS settings were also tailored for sensitivity increases, and the method allowed for analyte retention time and peak area repeatabilities of 0.1-0.4 % and 2-10 %, respectively, for a wide polarity range of metabolites (logP -4.4 to 8.8). The methods performance was suited for both untargeted analysis as well as targeted approaches, evaluated in clinically relevant experiments. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/21254119v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1179990org.highwire.dtl.DTLVardef@62eaa2org.highwire.dtl.DTLVardef@1a403dorg.highwire.dtl.DTLVardef@16f7648_HPS_FORMAT_FIGEXP M_FIG C_FIG
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