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Clinical Research
invalidating single features would not impede a sample quality de- 5. Sakamoto, K. et al. Ambient mass spectrometry-based detection
termination based on a multi-feature read-out. system for tumor cells in human blood. Transl. Cancer Res. 7, 758–
764; DOI:10.21037/tcr.2018.04.20 (2018).
Our aim was to determine whether PESI-MS has the potential
6. Saha, S., Mandal, M. K. & Hiraoka, K. Direct detection of trace level
to determine sample quality, for which one pre-analytical issue was
illicit drugs in human body fluids by probe electrospray ionization
used as proof-of-principle. Our results demonstrate that PESI-MS
mass spectrometry (PESI-MS). Anal. Methods 5, 4731–4738;
spectra contain multiple robust biomarkers. Additionally, many DOI:10.1039/c3ay41117f (2013).
other stable features were detected which renders detection of
7. Hainaut, P., Vaught, J., Zatloukal, K. & Pasterk, M. Biobanking of
robust biomarker for other pre-analytical highly likely. human biospecimens: Principles and practice. Biobanking Hum.
Biospecimens Princ. Pract. 1–239; DOI:10.1007/978-3-319-55120-3
(2017).
Conclusions 8. Kamlage, B. et al. Quality Markers Addressing Preanalytical Variations
of Blood and Plasma Processing Identified by Broad and Targeted
Metabolite Profiling. Clin. Chem. 60, 399–412; DOI:10.1373/
Our results provide a proof-of-concept that PESI-MS is a prom- clinchem.2013.211979 (2014).
ising technology for fast and comprehensive quality control of
9. Lippi, G. et al. Quality standards for sample collection in coagulation
blood samples. testing. Semin. Thromb. Hemost. 38, 565–75; DOI:10.1055/s-0032-
The single-step MeOH precipitation delivered ready-to-measure 1315961 (2012).
extracts in <8 min when manually performed and could be consid- 10. Kamlage, B. et al. Impact of Prolonged Blood Incubation and
erably speed-up with filtration and automatization. As little as 2 µl Extended Serum Storage at Room Temperature on the Human
Serum Metabolome. Metabolites 8, 6; DOI:10.3390/metabo
plasma sufficed for PESI-MS spectra in both ionization modes in
8010006 (2018).
2 min with 1200 stable features covering a broad chemical space.
11. Wagner-Golbs, A. et al. Effects of Long-Term Storage at −80 °C on
The time delay of 3 h was well predictable with five common
the Human Plasma Metabolome. Metabolites 9, 99; DOI:10.3390/
machine learning approaches based on 18 selected features with
metabo9050099 (2019).
an excellent AUC > 0.95 and was robust against failure of single
12. Yin, P. et al. Preanalytical aspects and sample quality assessment in
features. Although for a future high-throughput application more metabolomics studies of human blood. Clin. Chem. 59, 833–45;
optimization, reduction of noise and automatization are needed, DOI:10.1373/clinchem.2012.199257 (2013).
our results demonstrate the unique advantages of PESI-MS. The 13. Lehmann, R. Preanalytics: what can metabolomics learn from clinical
results pave the way towards a fully automated, cost-efficient, user- chemistry? Bioanalysis 7, 927–930; DOI:10.4155/bio.15.23 (2015).
friendly, robust and fast quality assessment of human blood sam- 14. Ghini, V., Quaglio, D., Luchinat, C. & Turano, P. NMR for sample
ples from minimal sample amounts. quality assessment in metabolomics. N. Biotechnol. 52, 25–34;
DOI:10.1016/j.nbt.2019.04.004 (2019).
15. Bordag, N. et al. Towards fast, routine blood sample quality evalua-
tion by Probe Electrospray Ionization (PESI) metabolomics. medRxiv
2021.04.18.21254782; DOI:10.1101/2021.04.18.21254782 (2021).
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