Simultaneous determination of β-hydroxybutyrate and β-hydroxy-β-methylbutyrate in human whole blood using hydrophilic interaction liquid chromatography electrospray tandem mass spectrometry

Clin Biochem. 2013 Dec;46(18):1877-83. doi: 10.1016/j.clinbiochem.2013.08.011. Epub 2013 Aug 29.

Abstract

Objectives: For the quantification of β-hydroxybutyrate (BHB) and β-hydroxy-β-methylbutyrate (HMB) in human whole blood, a method using hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) was developed, which does not require chemical modification of the analytes.

Design and methods: Samples were deproteinised by a mixture of methanol and acetonitrile, and the extracts were cleaned-up using both polymeric strong cation exchange and strong anion exchange sorbents. The analytes and their structural isomers were separated using a column with a zwitterionic stationary phase. Isotope dilution of both analytes was used for quantitative analysis.

Results: Separation of BHB from isobaric interferences was achieved through chromatography. The relative intra-laboratory reproducibility standard deviations were better than 10% for blood samples at concentration levels of 10-20μM BHB and 1μM HMB and better than 5% at concentration levels 10 times higher. The mean true extraction recoveries were close to 100%. The trueness expressed as the relative bias of test results was within ±5% at concentration levels of 10-1000μM BHB and 1-20μM HMB. The lower limits of quantification were estimated to be 3μM for BHB and 0.4μM for HMB.

Conclusions: A simple and highly sensitive and selective HILIC-MS/MS method was developed that is suitable for the quantification of BHB and HMB in whole blood.

Keywords: BHB; HMB; LC–MS/MS; Whole blood; β-Hydroxy-β-methylbutyrate; β-Hydroxybutyrate.

MeSH terms

  • 3-Hydroxybutyric Acid / blood*
  • Chromatography, Liquid / methods*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Limit of Detection
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Tandem Mass Spectrometry / methods*
  • Valerates / blood*

Substances

  • Valerates
  • beta-hydroxyisovaleric acid
  • 3-Hydroxybutyric Acid