MSACL 2016 US Abstract

Improved Sensitivity for Immunosuppressant Monitoring in Two Dried Matrices: A Proof of Concept

Jane Dickerson (Presenter)
Seattle Children's Hospital

Bio: Dr. Jane Dickerson completed her post-doctoral training at the University of Washington where she was a clinical chemistry fellow in the department of Lab Medicine. As a faculty member at Seattle Children’s and the University of Washington Department of Lab Medicine, she focuses her research on the science of the delivery of care – improving processes to get the right test ordered (utilization management), performed (analysis of alternative matrices), and resulted (failure to retrieve) for the best patient care.

Authorship: Cindy Gordon (1), Katerina Sadilkova (1), Rhona Jack (1,2), Jane Dickerson (1,2)
(1) Seattle Children's Hospital Department of Laboratories (2) University of Washington Department of Lab Medicine

Short Abstract

We aim to improve the clinical utility of remote collection of dried blood spots (DBS) for immunosuppressant monitoring with an enhanced method requiring less blood in both DBS and Mitra blood collection device. Immunosuppressants were quantified using deuterated internal standards on SCIEX QTRAP 6500. Limits of detection and quantitation were determined, with similar results using 3-mm DBS (3 µL) and Mitra device (10 µL). The method correlated well with previously published method using 8-mm DBS extractions. We believe this new method will eliminate the majority of rejected samples due to QNS and allow more families to participate in the remote monitoring program.

Long Abstract

Transplant patients are routinely and chronically monitored with laboratory testing to assess risk of rejection, infection, and to optimize therapeutic drug doses. Therapeutic drug monitoring of tacrolimus, sirolimus, and cyclosporine plays a significant role in the clinical follow-up of transplant patients receiving immunosuppressant (IMS) therapy. Success of transplant and favorable patient outcome relies on maintaining adequate therapeutic drug levels. Improving compliance (taking anti-rejection medication and getting regular lab draws) is a major effort for the clinical team caring for these patients. We developed, validated, and implemented a clinical liquid chromatography-mass spectrometry (LC-MS/MS) assay for simultaneous quantitation of tacrolimus, sirolimus, and cyclosporine in dried blood spots (DBS) collected remotely by patients and mailed into the laboratory (1). While popular and successful for many families, obtaining quality specimen is a barrier and more than 10% of submitted samples are rejected, requiring recollection (2). The purpose of this research is to improve the clinical utility of remote collection of dried blood spots for immunosuppressant monitoring with an enhanced method requiring less blood in both traditional dried blood spots and Mitra blood collection device.

The new method features all deuterated internal standards and analysis using a SCIEX QTRAP 6500, and is 50 times more sensitive. Limits of detection and quantitation were determined on the equivalent of 3 µL dried blood spot extractions, with similar results using the Mitra device (~10 µL). The method correlated well with previously published method using 8-mm (22 µL) dried blood spot extractions. We believe this new method will eliminate the majority of rejected samples due to QNS and ultimately, will allow more families to participate in the remote monitoring program.


References & Acknowledgements:

(1) Clin Chim Acta. 2013 Jun 5;421:152-6. doi: 10.1016/j.cca.2013.02.009

(2) Pediatr Transplant. 2015 Feb;19(1):101-6. doi: 10.1111/petr.12392


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