Comprehensive Evaluation of Blood Plasma and Serum Sample Preparations for HRMS-Based Chemical Exposomics: Overlaps and Specificities

Jade Chaker (1, 2) , David Møbjerg Kristensen (1, 3) , Thorhallur Ingi Halldorsson (4, 5) , Sjurdur Frodi Olsen (4, 6) , Christine Monfort (1) , Cécile Chevrier (1) , Bernard Jégou (1, 7) , Arthur David (1, 7, 8)

1 Irset - Institut de recherche en santé, environnement et travail
2 LERES - Laboratoire d'étude et de recherche en environnement et santé
3 Rigshospitalet [Copenhagen]
4 Statens Serum Institut [Copenhagen]
5 University of Iceland [Reykjavik]
6 Harvard T.H. Chan School of Public Health
7 EHESP - École des Hautes Études en Santé Publique [EHESP]
8 DEESSE - Département des sciences en santé environnementale

Sample preparation of biological samples can have a substantial impact on the coverage of small molecules detectable using liquid chromatography–high-resolution mass spectrometry (LC-HRMS). This initial step is particularly critical for the detection of externally derived chemicals and their metabolites (internal chemical exposome) generally present at trace levels. Hence, our objective was to investigate how blood sample preparation methods affect the detection of low-abundant chemicals and to propose alternative methods to improve the coverage of the internal chemical exposome. We performed a comprehensive evaluation of 12 sample preparation methods (SPM) using phospholipid and protein removal plates (PLR), solid phase extraction plates (SPE), supported liquid extraction cartridge (SLE), and conventionally used protein precipitation (PPT). We implemented new quantitative and qualitative criteria for nontargeted analyses (detection frequency, recoveries, repeatability, matrix effect, low-level spiking significance, method detection limits, throughput, and ease of use) to amply characterize these SPM in a step-by-step-type approach. As a final step, PPT and one PLR plate were applied to cohort plasma and serum samples injected in triplicate to monitor batch repeatability, and annotation was performed on the related data sets to compare the respective impacts of these SPM. We demonstrate that sample preparation significantly affects both the range of observable compounds and the level at which they can be observed (only 43%–54% of total features are overlapping between the two SPM). We propose to use PPT and PLR on the same samples by implementing a simple analytical workflow as their complementarity would allow the broadening of the visible chemical space.

Mots clés: Serum; Scanning probe microscopy; Sample preparation; Plasma; Extraction; Exposome

Domaines: Chimie analytique; Biochimie [q-bio.BM]

Jade Chaker, David Møbjerg Kristensen, Thorhallur Ingi Halldorsson, Sjurdur Frodi Olsen, Christine Monfort, et al.. Comprehensive Evaluation of Blood Plasma and Serum Sample Preparations for HRMS-Based Chemical Exposomics: Overlaps and Specificities. Analytical Chemistry, 2022, 94 (2), pp.866-874. ⟨10.1021/acs.analchem.1c03638⟩. ⟨hal-03543737⟩