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      Untargeted metabolomics profiling and hemoglobin normalization for archived newborn dried blood spots from a refrigerated biorepository.

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          Abstract

          Archived dried blood spots (DBS) following newborn screening are an attractive resource for interrogating early-life biology using untargeted metabolomics. Therefore, they have the potential to substantially aid etiological studies, particularly for rare and low-frequency childhood diseases and disorders. However, metabolite quantification in DBS is hindered by variation sources not present in serum and plasma samples such as the hematocrit effect and unknown initial blood volumes. Hemoglobin (Hb) is an appropriate correlate for hematocrit in experimentally-generated DBS punches. However, since many biorepositories worldwide archive DBS at 4-5 °C, there is a need to validate the utility of Hb for DBS archived under refrigeration. We evaluated two simple spectroscopic methods for measuring Hb in DBS stored at 4 +/- 2 °C for up to 21 years, obtained from the newborn screening program at the Karolinska University Hospital, Sweden. Spearman correlation analysis and Akaike Information Criterion model selection found that measurement of a Hb sodium lauryl sulfate complex at 540 nm better described nuisance variation than Hb measured at 404 nm, or using age of spot alone. This is the first study to profile metabolites and to propose a normalization factor for metabolite measurements from DBS archived for decades at 4 °C.

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          Author and article information

          Journal
          J Pharm Biomed Anal
          Journal of pharmaceutical and biomedical analysis
          Elsevier BV
          1873-264X
          0731-7085
          Nov 30 2020
          : 191
          Affiliations
          [1 ] Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States.
          [2 ] Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, SE 70182, Örebro, Sweden.
          [3 ] Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States; The Institute for Exposomic Research, Icahn School of Medicine at Mount Sinai, NY, 10029, United States.
          [4 ] Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, United States; The Institute for Exposomic Research, Icahn School of Medicine at Mount Sinai, NY, 10029, United States. Electronic address: lauren.petrick@mssm.edu.
          Article
          S0731-7085(20)31460-6 NIHMS1628461
          10.1016/j.jpba.2020.113574
          7899729
          32896810
          d3d15dfa-2c8d-4354-9aa7-4673bfd55939
          Copyright © 2020 Elsevier B.V. All rights reserved.
          History

          Dried blood spot,Hemoglobin,LC–MS,Metabolomics,Newborn screening,Sample storage

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