A rubber transfer gasket to improve the throughput of liquid-liquid extraction in 96-well plates: application to vitamin D testing

J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Jun 1;878(19):1639-42. doi: 10.1016/j.jchromb.2010.04.010. Epub 2010 Apr 24.

Abstract

Background: The unmitigated rise in demand for the assessment of vitamin D status has taxed the ability of clinical mass spectrometry laboratories to preserve turn-around times. We aimed to improve the throughput of liquid-liquid extraction of plasma/serum for the assay of 25-hydroxy vitamin D.

Methods: We designed and fabricated a flexible rubber gasket that seals two 96-well plates together to quantitatively transfer the contents of one plate to another. Using the transfer gasket and a dry-ice acetone bath to freeze the aqueous infranatant, we developed a novel liquid-liquid extraction workflow in a 96-well plate format. We applied the technology to the mass spectrometric quantification of 25-hydroxy vitamin D.

Results: Cross-contamination between wells was < or = 0.13%. The interassay imprecision over 132 days of clinical implementation was less than 10%. The method compared favorably to a standard liquid-liquid extraction in glass tubes (Deming slope=1.018, S(x|y)=0.022). The accuracy of the assay was 102-105% as assessed with the recently released control materials from NIST.

Conclusions: The development of a plate-sealing gasket permits the liquid-liquid extraction of clinical specimens in a moderate-throughput workflow and the reliable assay of vitamin D status. In the future, the gasket may also prove useful in other sample preparation techniques for HPLC or mass spectrometry.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemical Fractionation* / instrumentation
  • Chemical Fractionation* / methods
  • Chromatography, Reverse-Phase / methods
  • Humans
  • Regression Analysis
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry / methods
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood

Substances

  • Vitamin D
  • 25-hydroxyvitamin D