Xinyu Liu1,2, Miriam Hoene3, Peiyuan Yin1, Louise Fritsche4,5, Peter Plomgaard6,7, Jakob S Hansen7, Christos T Nakas8,9, Andreas M Niess10, Jens Hudemann10, Michael Haap11, Maimuna Mendy12, Cora Weigert3,5, Xiaolin Wang1, Andreas Fritsche3,4,5, Andreas Peter3,4,5, Hans-Ulrich Häring3,4,5, Guowang Xu13, Rainer Lehmann14,4,5. 1. CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China. 2. University of Chinese Academy of Sciences, Beijing, China. 3. Division of Clinical Chemistry and Pathobiochemistry (Central Laboratory), University Hospital Tübingen, Tübingen, Germany. 4. Core Facility German Center for Diabetes Research (DZD) Clinical Chemistry Laboratory, Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany. 5. German Center for Diabetes Research (DZD), Tübingen, Germany. 6. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark. 7. Center of Inflammation and Metabolism and Center for Physical Activity Research, Department of Infectious Diseases and Copenhagen Muscle Research Center (CMRC), Rigshospitalet, Copenhagen, Denmark. 8. University Institute of Clinical Chemistry, Center of Laboratory Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 9. Laboratory of Biometry, University of Thessaly, Volos, Greece. 10. Department of Sports Medicine, University Hospital Tübingen, Tübingen, Germany. 11. Department of Internal Medicine, Medical Intensive Care Unit, University of Tübingen, Tübingen, Germany. 12. Laboratory Services and Biobank Group, International Agency for Research on Cancer (IARC) of the World Health Organization (WHO), Lyon, France. 13. CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China; xugw@dicp.ac.cn rainer.lehmann@med.uni-tuebingen.de. 14. Division of Clinical Chemistry and Pathobiochemistry (Central Laboratory), University Hospital Tübingen, Tübingen, Germany; xugw@dicp.ac.cn rainer.lehmann@med.uni-tuebingen.de.
Abstract
BACKGROUND: Nonadherence to standard operating procedures (SOPs) during handling and processing of whole blood is one of the most frequent causes affecting the quality of serum and plasma. Yet, the quality of blood samples is of the utmost importance for reliable, conclusive research findings, valid diagnostics, and appropriate therapeutic decisions. METHODS: UHPLC-MS-driven nontargeted metabolomics was applied to identify biomarkers that reflected time to processing of blood samples, and a targeted UHPLC-MS analysis was used to quantify and validate these biomarkers. RESULTS: We found that (4E,14Z)-sphingadienine-C18-1-phosphate (S1P-d18:2) was suitable for the reliable assessment of the pronounced changes in the quality of serum and plasma caused by errors in the phase between collection and centrifugation of whole blood samples. We rigorously validated S1P-d18:2, which included the use of practicality tests on >1400 randomly selected serum and plasma samples that were originally collected during single- and multicenter trials and then stored in 11 biobanks in 3 countries. Neither life-threatening disease states nor strenuous metabolic challenges (i.e., high-intensity exercise) affected the concentration of S1P-d18:2. Cutoff values for sample assessment were defined (plasma, ≤0.085 μg/mL; serum, ≤0.154 μg/mL). CONCLUSIONS: Unbiased valid monitoring to check for adherence to SOP-dictated time for processing to plasma or serum and/or time to storage of whole blood at 4 °C is now feasible. This novel quality assessment step could enable scientists to uncover common preanalytical errors, allowing for identification of serum and plasma samples that should be excluded from certain investigations. It should also allow control of samples before long-term storage in biobanks.
BACKGROUND: Nonadherence to standard operating procedures (SOPs) during handling and processing of whole blood is one of the most frequent causes affecting the quality of serum and plasma. Yet, the quality of blood samples is of the utmost importance for reliable, conclusive research findings, valid diagnostics, and appropriate therapeutic decisions. METHODS: UHPLC-MS-driven nontargeted metabolomics was applied to identify biomarkers that reflected time to processing of blood samples, and a targeted UHPLC-MS analysis was used to quantify and validate these biomarkers. RESULTS: We found that (4E,14Z)-sphingadienine-C18-1-phosphate (S1P-d18:2) was suitable for the reliable assessment of the pronounced changes in the quality of serum and plasma caused by errors in the phase between collection and centrifugation of whole blood samples. We rigorously validated S1P-d18:2, which included the use of practicality tests on >1400 randomly selected serum and plasma samples that were originally collected during single- and multicenter trials and then stored in 11 biobanks in 3 countries. Neither life-threatening disease states nor strenuous metabolic challenges (i.e., high-intensity exercise) affected the concentration of S1P-d18:2. Cutoff values for sample assessment were defined (plasma, ≤0.085 μg/mL; serum, ≤0.154 μg/mL). CONCLUSIONS: Unbiased valid monitoring to check for adherence to SOP-dictated time for processing to plasma or serum and/or time to storage of whole blood at 4 °C is now feasible. This novel quality assessment step could enable scientists to uncover common preanalytical errors, allowing for identification of serum and plasma samples that should be excluded from certain investigations. It should also allow control of samples before long-term storage in biobanks.
Authors: Bo Burla; Makoto Arita; Masanori Arita; Anne K Bendt; Amaury Cazenave-Gassiot; Edward A Dennis; Kim Ekroos; Xianlin Han; Kazutaka Ikeda; Gerhard Liebisch; Michelle K Lin; Tze Ping Loh; Peter J Meikle; Matej Orešič; Oswald Quehenberger; Andrej Shevchenko; Federico Torta; Michael J O Wakelam; Craig E Wheelock; Markus R Wenk Journal: J Lipid Res Date: 2018-08-16 Impact factor: 5.922
Authors: Candice Z Ulmer; Jeremy P Koelmel; Christina M Jones; Timothy J Garrett; Juan J Aristizabal-Henao; Hubert W Vesper; John A Bowden Journal: Lipids Date: 2020-06-09 Impact factor: 1.646