Dried blood spot validation of five immunosuppressants, without hematocrit correction, on two LC-MS/MS systems

Bioanalysis. 2017 Apr;9(7):553-563. doi: 10.4155/bio-2016-0296. Epub 2017 Mar 16.

Abstract

Aim: Hematocrit (Ht) effects remain a challenge in dried blood spot (DBS) sampling. The aim was to develop an immunosuppressant DBS assay on two LC-MS/MS systems covering a clinically relevant Ht range without Ht correction.

Results: The method was partially validated for tacrolimus, sirolimus, everolimus, cyclosporin A and fully validated for mycophenolic acid on an Agilent and Thermo LC-MS/MS system. Bias caused by Ht effects were within 15% for all immunosuppressants between Ht levels of 0.23 and 0.48 l/l. Clinical validation of DBS versus whole blood samples for tacrolimus and cyclosporin A showed no differences between the two matrices.

Conclusion: A multiple immunosuppressant DBS method without Ht correction, has been validated, including a clinical validation for tacrolimus and cyclosporin A, making this procedure suitable for home sampling.

Keywords: DBS; clinical validation; cyclosporine A; dried blood spot; everolimus; hematocrit effect; immunosuppressants; mycophenolic acid; sirolimus; tacrolimus.

Publication types

  • Validation Study

MeSH terms

  • Chromatography, Liquid / methods*
  • Cyclosporine / blood
  • Dried Blood Spot Testing / methods*
  • Drug Monitoring / methods*
  • Everolimus / blood
  • Hematocrit
  • Humans
  • Immunosuppressive Agents / blood*
  • Mycophenolic Acid / blood
  • Sirolimus / blood
  • Tacrolimus / blood
  • Tandem Mass Spectrometry / methods*

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Everolimus
  • Mycophenolic Acid
  • Sirolimus
  • Tacrolimus