Cobalamin Concentrations in Fetal Liver Show Gender Differences: A Result from Using a High-Pressure Liquid Chromatography−Inductively Coupled Plasma Mass Spectrometry as an Ultratrace Cobalt Speciation Method

Janine  Bosle; Sven Goetz; Andrea Raab; Eva M. Krupp; Kirk G. Scheckel; Enzo Lombi; Andrew A. Meharg; Paul A. Fowler; Joerg Feldmann

doi:10.1021/acs.analchem.6b03730

Cobalamin Concentrations in Fetal Liver Show Gender Differences: A Result from Using a High-Pressure Liquid Chromatography−Inductively Coupled Plasma Mass Spectrometry as an Ultratrace Cobalt Speciation Method

Janine Bosle, Sven Goetz, Andrea Raab, Eva M. Krupp, Kirk G. Scheckel, Enzo Lombi, Andrew A. Meharg, Paul A. Fowler, Joerg Feldmann

Research output: Contribution to journal › Article

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Abstract

Maternal diet and lifestyle choices may affect placental transfer of cobalamin (Cbl) to the fetus. Fetal liver concentration of Cbl reflects nutritional status with regards to vitamin B12, but at these low concentration current Cbl measurement methods lack robustness. An analytical method based on enzymatic extraction with subsequent reversed-phasehigh-pressure liquid chromatography (RP-HPLC) separation and parallel ICPMS and electrospray ionization (ESI)-Orbitrap-MS to determine specifically Cbl species in liver samples of only 10−50 mg was developed using 14 pig livers. Subsequently 55 human fetal livers were analyzed. HPLC−ICPMS analysis for cobalt (Co) and Cbl gave detection limits of 0.18 ng/g and 0.88 ng/g d.m. in liver samples, respectively, with a recovery of >95%. Total Co (Cot) concentration did not reflect the amount of Cbl or vitamin B12 in the liver. Cbl bound Co contributes only 45 ± 15% to Cot. XRF mapping and μXANES analysis confirmed the occurrence of non-Cbl cobalt in pig liver hot spots indicating particular Co. No correlations of total cobalt nor Cbl with fetal weight or weeks of gestation were found for the human fetal livers. Although no gender difference could be identified for total Co concentration, female livers were significantly higher in Cbl concentration (24.1 ± 7.8 ng/g) than those from male fetuses (19.8 ± 7.1 ng/g) (p = 0.04). This HPLC−ICPMS method was able to quantify total Cot and Cbl in fetus liver, and it was sensitive and precise enough to identify this gender difference.

Original language	English
Pages (from-to)	12419–12426
Number of pages	8
Journal	Analytical Chemistry
Volume	88
Issue number	24
Early online date	21 Nov 2016
DOIs	https://doi.org/10.1021/acs.analchem.6b03730
Publication status	Published - 20 Dec 2016

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This document is the Accepted Manuscript version of a Published Work that appeared in final form in Analytical Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.analchem.6b03730
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Paul Alfred François Fowler

School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Director of Institute of Medical Science
Clinical Medicine
School of Medicine, Medical Sciences & Nutrition, Applied Medicine - Chair in Translational Medical Sciences
Institute of Medical Sciences

Person: Academic

Cite this

Bosle, J., Goetz, S., Raab, A., Krupp, E. M., Scheckel, K. G., Lombi, E., Meharg, A. A., Fowler, P. A., & Feldmann, J. (2016). Cobalamin Concentrations in Fetal Liver Show Gender Differences: A Result from Using a High-Pressure Liquid Chromatography−Inductively Coupled Plasma Mass Spectrometry as an Ultratrace Cobalt Speciation Method. Analytical Chemistry, 88(24), 12419–12426. https://doi.org/10.1021/acs.analchem.6b03730

Cobalamin Concentrations in Fetal Liver Show Gender Differences : A Result from Using a High-Pressure Liquid Chromatography−Inductively Coupled Plasma Mass Spectrometry as an Ultratrace Cobalt Speciation Method. / Bosle, Janine ; Goetz, Sven; Raab, Andrea ; Krupp, Eva M.; Scheckel, Kirk G.; Lombi, Enzo; Meharg, Andrew A.; Fowler, Paul A.; Feldmann, Joerg.

In: Analytical Chemistry, Vol. 88, No. 24, 20.12.2016, p. 12419–12426.

Research output: Contribution to journal › Article

Bosle, J, Goetz, S, Raab, A , Krupp, EM, Scheckel, KG, Lombi, E, Meharg, AA, Fowler, PA & Feldmann, J 2016, 'Cobalamin Concentrations in Fetal Liver Show Gender Differences: A Result from Using a High-Pressure Liquid Chromatography−Inductively Coupled Plasma Mass Spectrometry as an Ultratrace Cobalt Speciation Method', Analytical Chemistry, vol. 88, no. 24, pp. 12419–12426. https://doi.org/10.1021/acs.analchem.6b03730

Bosle J, Goetz S, Raab A , Krupp EM, Scheckel KG, Lombi E et al. Cobalamin Concentrations in Fetal Liver Show Gender Differences: A Result from Using a High-Pressure Liquid Chromatography−Inductively Coupled Plasma Mass Spectrometry as an Ultratrace Cobalt Speciation Method. Analytical Chemistry. 2016 Dec 20;88(24):12419–12426. https://doi.org/10.1021/acs.analchem.6b03730

Bosle, Janine ; Goetz, Sven ; Raab, Andrea ; Krupp, Eva M. ; Scheckel, Kirk G. ; Lombi, Enzo ; Meharg, Andrew A. ; Fowler, Paul A. ; Feldmann, Joerg. / Cobalamin Concentrations in Fetal Liver Show Gender Differences : A Result from Using a High-Pressure Liquid Chromatography−Inductively Coupled Plasma Mass Spectrometry as an Ultratrace Cobalt Speciation Method. In: Analytical Chemistry. 2016 ; Vol. 88, No. 24. pp. 12419–12426.

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title = "Cobalamin Concentrations in Fetal Liver Show Gender Differences: A Result from Using a High-Pressure Liquid Chromatography−Inductively Coupled Plasma Mass Spectrometry as an Ultratrace Cobalt Speciation Method",

abstract = "Maternal diet and lifestyle choices may affect placental transfer of cobalamin (Cbl) to the fetus. Fetal liver concentration of Cbl reflects nutritional status with regards to vitamin B12, but at these low concentration current Cbl measurement methods lack robustness. An analytical method based on enzymatic extraction with subsequent reversed-phasehigh-pressure liquid chromatography (RP-HPLC) separation and parallel ICPMS and electrospray ionization (ESI)-Orbitrap-MS to determine specifically Cbl species in liver samples of only 10−50 mg was developed using 14 pig livers. Subsequently 55 human fetal livers were analyzed. HPLC−ICPMS analysis for cobalt (Co) and Cbl gave detection limits of 0.18 ng/g and 0.88 ng/g d.m. in liver samples, respectively, with a recovery of >95%. Total Co (Cot) concentration did not reflect the amount of Cbl or vitamin B12 in the liver. Cbl bound Co contributes only 45 ± 15% to Cot. XRF mapping and μXANES analysis confirmed the occurrence of non-Cbl cobalt in pig liver hot spots indicating particular Co. No correlations of total cobalt nor Cbl with fetal weight or weeks of gestation were found for the human fetal livers. Although no gender difference could be identified for total Co concentration, female livers were significantly higher in Cbl concentration (24.1 ± 7.8 ng/g) than those from male fetuses (19.8 ± 7.1 ng/g) (p = 0.04). This HPLC−ICPMS method was able to quantify total Cot and Cbl in fetus liver, and it was sensitive and precise enough to identify this gender difference.",

author = "Janine Bosle and Sven Goetz and Andrea Raab and Krupp, {Eva M.} and Scheckel, {Kirk G.} and Enzo Lombi and Meharg, {Andrew A.} and Fowler, {Paul A.} and Joerg Feldmann",

note = "Chief Scientist Office (Scottish Executive, Grant CZG/1/109 (P.A.F.) and Grant CZG/4/742 (P.A.F.); NHS Grampian Endowments 08/02 (P.A.F.); the European Community{\textquoteright}s Seventh Framework Programme (Grant FP7/2007-2013) under Grant Agreement No. 212885 (P.A.F.); and the Medical Research Council Grant MR/L010011/1 (P.A.F.).",

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T2 - A Result from Using a High-Pressure Liquid Chromatography−Inductively Coupled Plasma Mass Spectrometry as an Ultratrace Cobalt Speciation Method

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AU - Goetz, Sven

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AU - Lombi, Enzo

AU - Meharg, Andrew A.

AU - Fowler, Paul A.

AU - Feldmann, Joerg

N1 - Chief Scientist Office (Scottish Executive, Grant CZG/1/109 (P.A.F.) and Grant CZG/4/742 (P.A.F.); NHS Grampian Endowments 08/02 (P.A.F.); the European Community’s Seventh Framework Programme (Grant FP7/2007-2013) under Grant Agreement No. 212885 (P.A.F.); and the Medical Research Council Grant MR/L010011/1 (P.A.F.).

PY - 2016/12/20

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N2 - Maternal diet and lifestyle choices may affect placental transfer of cobalamin (Cbl) to the fetus. Fetal liver concentration of Cbl reflects nutritional status with regards to vitamin B12, but at these low concentration current Cbl measurement methods lack robustness. An analytical method based on enzymatic extraction with subsequent reversed-phasehigh-pressure liquid chromatography (RP-HPLC) separation and parallel ICPMS and electrospray ionization (ESI)-Orbitrap-MS to determine specifically Cbl species in liver samples of only 10−50 mg was developed using 14 pig livers. Subsequently 55 human fetal livers were analyzed. HPLC−ICPMS analysis for cobalt (Co) and Cbl gave detection limits of 0.18 ng/g and 0.88 ng/g d.m. in liver samples, respectively, with a recovery of >95%. Total Co (Cot) concentration did not reflect the amount of Cbl or vitamin B12 in the liver. Cbl bound Co contributes only 45 ± 15% to Cot. XRF mapping and μXANES analysis confirmed the occurrence of non-Cbl cobalt in pig liver hot spots indicating particular Co. No correlations of total cobalt nor Cbl with fetal weight or weeks of gestation were found for the human fetal livers. Although no gender difference could be identified for total Co concentration, female livers were significantly higher in Cbl concentration (24.1 ± 7.8 ng/g) than those from male fetuses (19.8 ± 7.1 ng/g) (p = 0.04). This HPLC−ICPMS method was able to quantify total Cot and Cbl in fetus liver, and it was sensitive and precise enough to identify this gender difference.

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