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Use of an automated dried blood spot method for therapeutic drug monitoring of immunosuppressants

Patients receiving a solid organ transplant often require a lifetime of immunosuppressant therapy to prevent allograft rejection. By optimizing a patient’s immunosuppressant therapy, one-year graft survival rates increased to up to 97 percent for living donor transplant recipients in 2017, according to the United States Renal Data System. Therapeutic drug monitoring (TDM) can determine the optimal dose of immunosuppressant for a patient. TDM is important because immunosuppressant drugs have a wide variation in interindividual and intraindividual pharmacokinetics and a narrow therapeutic range. These factors necessitate frequent patient monitoring, which means that patients must make many trips to a hospital or blood draw center to have their blood drawn and analyzed for immunosuppressant concentrations. This potentially can be minimized by at-home dried blood microsampling, which involves patients sending samples to the laboratory via regular postal mail. However, lack of automated methods in clinical labs that perform routine testing pose a challenge to implementing this methodology. The authors conducted a study to compare a fully automated dried blood spot extraction method to venous whole blood manual extraction methods for tacrolimus, sirolimus, everolimus, and cyclosporin A. Blood samples from healthy volunteers were spiked with the drugs and run on a liquid chromatography platform coupled to tandem mass spectrometry. A Bland-Altman comparison was used to assess agreement between the automated dried blood spot and manual extraction whole blood methods. The analytical acceptance limit was based on the European Medicine Agency’s criterion for incurred sample reanalysis that at least 67 percent of all paired samples be within 20 percent of the mean of both samples. Clinical acceptance limits required that at least 80 percent of all paired samples be within 20 percent of the whole blood concentration of the sample. The results showed that the hematocrit impacted dried blood spot quantitation for all analytes. However, this could be alleviated using a formula based on the tacrolimus data subset: dried blood spot_corrected = dried blood spot_measured/(1.6305 -1.559*hct). Both analytical and clinical acceptance criteria were met by correcting the formula. The authors concluded that automated dried blood spot analysis has a potential to ease the burden of routine therapeutic drug monitoring of immunosuppressants, negating the need for manual extraction methods. However, additional clinical validation studies, involving capillary finger prick samples, are necessary to demonstrate the applicability of the method in a real-life setting.

Deprez S, Stove C. Application of a fully automated dried blood spot method for therapeutic drug monitoring of immunosuppressants: Another step toward implementation of dried blood spot analysis. Arch Pathol Lab Med. 2023;147:786–796.

Correspondence: Dr. Christophe Stove at christophe.stove@ugent.be