Dried Blood Spot Validation of Five Immunosuppressants, Without Hematocrit Correction, on Two LC–MS/MS Systems

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::

• clinical validation
• cyclosporine A
• DBS
• dried blood spot
• everolimus
• hematocrit effect
• immunosuppressants
• mycophenolic acid
• sirolimus
• tacrolimus

Financial & competing interests disclosure

This work was supported by the Netherlands Organization for Health Research and Development (ZonMw, The Hague, Netherlands) grant 836044004. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors would like to thank the phlebotomists of the ‘Prikpoli’ of the UMCG for obtaining the clinical samples.

Additional information

Funding

This work was supported by the Netherlands Organization for Health Research and Development (ZonMw, The Hague, Netherlands) grant 836044004. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.