Alkali dilution of blood samples for high throughput ICP-MS analysis-comparison with acid digestion

Clin Biochem. 2015 Feb;48(3):140-7. doi: 10.1016/j.clinbiochem.2014.12.003. Epub 2014 Dec 9.


Objectives: The direct dilution of blood with alkali has been introduced as an alternative to acid digestion for improvement of the analytical productivity when measuring trace elements using inductively coupled plasma mass spectrometry (ICP-MS). This study compared these two sample preparation methods for the ICP-MS determination of multiple elements in human blood and serum.

Methods: Aliquots (0.2 or 0.5 mL) of human whole blood and serum samples, including reference samples (whole blood and serum), were subjected to alkali dilution (ammonia solution) or acid digestion (nitric acid). The samples were then analysed for their concentrations of Li, B, Mg, P, S, K, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Mo, Cd, Sb, Cs, Ba, Pb and U with a quadrupole ICP-MS instrument equipped with a collision/reaction cell.

Results: Analysis of the reference materials showed that the alkali dilution and acid digestion methods provided equally good agreement with the reference values for Mg, Mn, Co, Ni, Cu, Zn, As, Se, Rb, Mo, Cd, Sb and Pb. The alkali dilution method generally gave better agreement with the reference values for Li, B, P, S, K, Cr and U, whereas acid digestion gave better agreement for Ca, Fe, Sr and Cs. Strong associations (R(2)>0.90) between the two methods were obtained for the concentrations of Li, B, Mn, Co, Cu, As, Se, Rb, Sr, Mo, Cd, Cs and Pb in the collected human whole blood and for Li, B, Mg, P, S, K, Fe, Co, Cu, Zn, As, Se, Rb, Sr, Sb and Cs in the collected serum.

Conclusions: The results suggest that the alkali dilution method is suitable for the determination of Li, B, Mn, Co, Cu, Zn, As, Se, Rb and Sr in whole blood and serum; Mo, Cd and Pb in whole blood; and Sb in serum by ICP-MS. Acid digestion is preferred for Fe and for low concentrations of Cs.

Keywords: Acid digestion; Alkali dilution; Human serum; Human whole blood; Inductively coupled plasma mass spectrometry; Multi-element.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ammonia / chemistry*
  • Calibration
  • Female
  • High-Throughput Screening Assays / methods*
  • Humans
  • Limit of Detection
  • Linear Models
  • Nitric Acid / chemistry*
  • Pregnancy
  • Reference Standards
  • Spectrophotometry, Atomic / methods*
  • Trace Elements / blood*


  • Trace Elements
  • Nitric Acid
  • Ammonia