Comparison of untargeted chemical profiles of dried blood spots, dried blood microsamplers, and plasma

Background and aim: Capillary blood collection is minimally invasive, easy to perform, and when dried, is more stable at higher temperatures than liquid blood, making dried capillary blood microsamplers a promising alternative to venous blood for epidemiological research. To evaluate the utility of dried blood samplers for use in exposome studies, comparisons of metabolite profiles between capillary dried blood and conventional plasma collection are needed. Methods: Commercially purchased whole blood from a single adult smoker was used for experiments. Dried blood spots were generated by pipetting 50 µL for 5-mm punches, 10 µL VAMS were generated from the whole blood following manufacturer’s instructions, and 10 µL plasma aliquots were generated by centrifugation. Samples were stored overnight at -80C. Triplicate samples were randomized and analyzed for each device using Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS). Metabolites were identified using Agilent Profinder software. Metabolite levels (abundance) were compared for each sample type using a one-way ANOVA and fold change (FC). Results: We identified 305 metabolites from LC-HRMS analysis. Among those compounds, 222 metabolites show significant differences in abundance among Guthrie, VAMS, and plasma samples (p value<0.05). 42 compounds have higher abundance (>3 FC) in Guthrie or VAMS than plasma samples. Among these compounds, carboxylic acids and derivatives (7) and organooxygen compounds (7) are the major compound classes, but also included two metabolites of alcohol exposure. Three compounds have a higher abundance (>3 FC) in plasma than Guthrie or VAMS. Conclusions: Several metabolites have a higher abundance in Guthrie or VAMS than in plasma samples. However, most compounds showed a comparable fold change among these three sample types. Depending on the group of metabolites or exogenous compounds of interest, microsampling devices are an alternative to conventional plasma collection for exposome studies. Keywords: Untargeted chemical analysis, dried blood spots, microsamplers, exposome.