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Evaluation of a coated blade spray-tandem mass spectrometry assay as a new tool for the determination of immunosuppressive drugs in whole blood

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Abstract

Immunosuppressive drugs (ISDs) are primarily administered following solid organ transplant or for treatment of a variety of autoimmune conditions. Their principal function is to suppress the activity of the immune system; however, the levels must be carefully monitored due to adverse effects of over- or underadministration. A technology for rapid quantitative screening, named coated blade spray (CBS), was directly coupled to a triple quadrupole mass spectrometer (MS/MS) to measure the concentration of ISDs (i.e., cyclosporine A, tacrolimus, everolimus, sirolimus) in whole blood samples. We evaluated the stability of replicate measurements over a 10-day period (precision), assessed linearity and limit of quantification, and performed a method comparison against a validated clinical immunoassay (Abbott ARCHITECT). Total interday variation of less than 5% for all target compounds at three different concentrations was achieved. The sensitivity of the method was determined as 0.25, 1, 1, and 2.5 ng/mL for everolimus, sirolimus, tacrolimus, and cyclosporine A, respectively. The concentrations of three immunosuppressive drugs in 284 patient samples (i.e., ~ 95 samples of cyclosporine A, tacrolimus, or sirolimus) obtained using the CBS-MS/MS methodology were compared with concentrations previously quantified on an Abbott ARCHITECT immunoassay system. Our analysis demonstrated significant statistical similarities between both methods. The results demonstrate that CBS-MS/MS is a suitable alternative to conventional methodologies for monitoring of ISDs from whole blood in a clinical setting.

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Acknowledgments

We would like to acknowledge Thermo Scientific for providing the TSQ Quantiva and Waters Corporation for supplying the HLB particles.

Funding

DR, GAGR, MT, EN, and JP would like to thank the Natural Sciences and Engineering Research Council (NSERC) of Canada and Restek Corporation for their financial support through the Industrial Research Chair program and the associated industrial research partnership.

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Correspondence to Vathany Kulasingam or Janusz B. Pawliszyn.

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Conflict of interest

G.A. Gómez-Ríos and J.B. Pawliszyn are co-inventors of the coated blade spray (US patent: 9733234), while JP Scientific Limited holds ownership over this patent. The patent has now been licensed to Restek Corporation. 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. All authors claim no nonfinancial conflict of interest in the submitted manuscript.

Research involving human participants

Human whole blood specimens were collected from patients undergoing immunosuppressant therapy at the University Health Network (UHN; Toronto, ON, Canada). Informed consent was obtained prior to specimen collection, and ethics approval was waived by the Research Ethics Board at UHN for use of routine-collected specimens for the evaluation of method performance.

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Published in the topical collection Euroanalysis XX with guest editor Sibel A. Ozkan.

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Rickert, D.A., Gómez-Ríos, G.A., Nazdrajić, E. et al. Evaluation of a coated blade spray-tandem mass spectrometry assay as a new tool for the determination of immunosuppressive drugs in whole blood. Anal Bioanal Chem 412, 5067–5076 (2020). https://doi.org/10.1007/s00216-019-02367-z

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  • DOI: https://doi.org/10.1007/s00216-019-02367-z

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