Source Title:
Clinical Chemistry and Laboratory Medicine (CCLM)
|
Volume/Issue:
Volume 54: Issue 7

Measurement of plasma vitamin K1 (phylloquinone) and K2 (menaquinones-4 and -7) using HPLC-tandem mass spectrometry

Ineke J. Riphagenhttp://orcid.org/0000-0001-5500-0145, Jan C. van der Molen 3 , Martijn van Faassen 3 , Gerjan Navis 1 , Martin H. de Borst 1 , Frits A.J. Muskiet 3 , Wilhelmina H.A. de Jong 3 , Stephan J.L. Bakker, and Ido P. Kema 3
  • 1 Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  • 2 Top Institute Food and Nutrition, Wageningen, The Netherlands
  • 3 Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Ineke J. RiphagenORCID iD: http://orcid.org/0000-0001-5500-0145, Jan C. van der Molen, Martijn van Faassen, Gerjan Navis, Martin H. de Borst, Frits A.J. Muskiet, Wilhelmina H.A. de Jong, Stephan J.L. Bakker and Ido P. Kema
DOI:
https://doi.org/10.1515/cclm-2015-0864
|
Published online:
02 Dec 2015

Abstract

Background: Given the growing interest in the health benefits of vitamin K, there is great need for development of new high-throughput methods for quantitative determination of vitamin K in plasma. We describe a simple and rapid method for measurement of plasma vitamin K1 (phylloquinone [PK]) and K2 (menaquinones [MK]-4 and -7). Furthermore, we investigated the association of fasting plasma vitamin K with functional vitamin K insufficiency in renal transplant recipients (RTR).

Methods: We used HPLC-tandem mass spectrometry with atmospheric pressure chemical ionization for measurement of plasma PK, MK-4, and MK-7. Solid-phase extraction was used for sample clean-up. Mass spectrometric detection was performed in multiple reaction monitoring mode. Functional vitamin K insufficiency was defined as plasma desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) >500 pmol/L.

Results: Lower limits of quantitation were 0.14 nmol/L for PK and MK-4 and 4.40 nmol/L for MK-7. Linearity up to 15 nmol/L was excellent. Mean recoveries were >92%. Fasting plasma PK concentration was associated with recent PK intake (ρ=0.41, p=0.002) and with plasma MK-4 (ρ=0.49, p<0.001). Plasma PK (ρ=0.38, p=0.003) and MK-4 (ρ=0.46, p<0.001) were strongly correlated with plasma triglyceride concentrations. Furthermore, we found that MK-4-triglyceride ratio, but not PK-triglyceride ratio, was significantly associated with functional vitamin K insufficiency (OR 0.22 [0.07–0.70], p=0.01) in RTR.

Conclusions: The developed rapid and easy-to-use LC-MS/MS method for quantitative determination of PK, MK-4, and MK-7 in human plasma may be a good alternative for the labor-intensive and time-consuming LC-MS/MS methods and enables a higher sample throughput.

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Article information

Corresponding author: Ineke J. Riphagen, Division of Nephrology Department of Internal Medicine, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands, Phone: +31 50 361 6161; Fax: +31 50 361 9310, E-mail: . http://orcid.org/0000-0001-5500-0145; Top Institute Food and Nutrition, Wageningen, The Netherlands; Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

Received:
2015-09-04
Accepted:
2015-10-24
Published Online:
2015-12-02
Published in Print:
2016-07-01

Citation Information: 
Clinical Chemistry and Laboratory Medicine (CCLM), Volume 54, Issue 7, Pages 1201–1210, eISSN 1437-4331, ISSN 1434-6621, DOI: https://doi.org/10.1515/cclm-2015-0864.

©2016 by De Gruyter.

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Journal + Issues

Clinical Chemistry and Laboratory Medicine (CCLM)

Online ISSN:
1437-4331
First published:
01 Jan 1963
Language:
English
Publisher:
De Gruyter

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