the viability of Mitra devices for therapeutic drug monitoring

As the demand for easier access to a wider pool of study participants and more accessible healthcare continues to grow, remote blood sampling for therapeutic drug monitoring (TDM) has become an increasingly vital tool for assessing and managing patients on immunosuppressive therapies.

A recent study poster from researchers at LabExperts Sp. z o.o. and Bioanalytic Sp. z o.o. and their collaborators in Poland explores the viability of using Mitra^® devices based on VAMS^® technology for remote blood sampling in TDM applications.

For this study, the researchers evaluated the use of dried blood samples for monitoring Tacrolimus (TAC), Sirolimus (SIR), Everolimus (EVR), and Cyclosporin A (CSA) — all critical immunosuppressants, typically prescribed to patients who have received organ transplants to prevent organ rejection. These medications must be monitored regularly to determine if individual dosing needs to be adjusted to ensure drug efficacy and avoid drug toxicity.

In this blog, we summarize the remote blood sampling study's objectives, methods, results, and conclusions, highlighting the potential of Mitra devices with VAMS technology (Mitra-VAMS devices) as a solution for remote TDM of immunosuppressants.

The Challenge of Therapeutic Drug Monitoring

Therapeutic drug monitoring (TDM) is crucial for patients using immunosuppressant medications, as the right dosage is essential to prevent rejection of transplanted organs, avoid drug toxicity, and achieve optimal therapeutic effects. However, drug concentrations in blood can fluctuate over time, requiring frequent blood sampling to adjust doses accordingly. Remote blood sampling has been shown in published studies to be particularly beneficial in this context, as patients or study participants can collect samples at home without the need to visit a clinic.

Traditional liquid venous blood samples collected remotely require cold shipping and special handling, which can be expensive. Dried blood sampling, however, offers a solution to these issues, enabling patients to collect dried blood spot (DBS) samples at home using a kit that provides the device and supplies needed for a simple finger-stick method.

Since these are dried blood samples, people can send their home-collected samples directly to the laboratory via mail without the need for cold shipping. The success of this method depends on the stability of the analytes and ease with which the lab team can accurately process and analyze these dried samples in the lab.

Study Objective: Evaluating Mitra Devices for Remote Blood Sampling in TDM

In this study, the researchers aimed to investigate the feasibility of using Mitra-VAMS devices in the commercially available CE-IVD assay kits from ChromSystems to collect dried blood samples for home-based TDM of immunosuppressants. The primary goal was to determine if dried blood samples collected with Mitra devices achieved validation criteria that correlated with venous blood samples for measuring immunosuppressant drug levels.

The researchers sought to confirm that the remote blood sampling kits using the Mitra device could facilitate self-sampling by patients.

Methods: Sample Collection and Analysis

The study followed a well-structured methodology to assess the viability of Mitra-VAMS devices for this purpose.

1. Sample Collection: Venous blood samples were collected from 15 patients for each compound (Tacrolimus, Sirolimus, Cyclosporin A). In parallel, dried blood samples were collected using 10 µL Mitra VAMS devices. The sample preparation for venous blood was done according to the Chromsystems kit procedure (kit #93000).

2. Sample Preparation for Mitra Devices: The preparation of dried blood samples collected with Mitra devices involved sonication, vortexing, and the addition of internal standards combined with an extraction buffer. The extraction process was standardized using only reagents supplied by the manufacturer.

3. Analysis: The blood samples were analyzed using the QTRAP 5500+ LC-MS/MS system (SCIEX), which provided precise quantitation of the immunosuppressant drugs. Data processing and statistical analysis were carried out using SciexOS 3.3 software.

Results: Validation and Correlation of Blood Samples

The study’s findings provided valuable insights into the performance of the Mitra device for remote TDM applications. Here are the key results:

1. Validation Criteria: The procedure for preparing Mitra microsamples met all validation criteria, including:

   • Reproducibility (%CV±15% and accuracy between 85-115%)
   • Limit of Quantification (LLOQ) with a signal-to-noise ratio (S/N) ≥10
   • Linearity of results (R ≥ 0.995)
     
     

2. Dried Blood Sample Stability: The study found that 10 µL Mitra samples provided stable readings, with lower-than-50 pg/mL concentrations achieved for each immunosuppressant drug. The Limit of Detection (LOD) was not determined, but the 10 µL Mitra sample yielded reliable results at concentrations below this threshold.

3. Venous Blood vs. Mitra (VB/M) Correlation: The preliminary correlation study found that Tacrolimus (TAC) and Sirolimus (SIR) concentrations in capillary blood were lower than in venous blood, while Cyclosporin A (CSA) showed higher concentrations in capillary blood compared to venous blood. Specifically, the VB/M factors were as follows:

   • TAC = 0.75, %CV = 22.92%
   • SIR = 0.77, %CV = 36.10%
   • CSA = 1.15, %CV = 19.01%

These findings suggest that TAC and SIR are more likely to enter erythrocytes (red blood cells) in higher concentrations (around 90%), while CSA enters erythrocytes to a lesser degree (about 50%). The capillary blood used in the Mitra device showed a higher proportion of serum relative to whole blood.

Study Author's Conclusions: Mitra Is a Promising Solution for Remote TDM

The study concluded that the Mitra device based on VAMS technology is a viable sample collection tool for remote therapeutic drug monitoring (TDM), specifically for immunosuppressant medications utilizing the Chromsystems CE-IVD TDM Kit. The optimized sample preparation procedure met validation criteria, and the additional steps required for Mitra sample preparation were simple, robust, and automation friendly.

The correlation data indicated that, while the concentrations of Tacrolimus and Sirolimus were lower in capillary blood than in venous blood, Cyclosporin A showed the opposite trend, with higher concentrations in capillary blood. The study recommends further investigation with a larger patient population and more comprehensive statistical analysis to refine these findings.

This is curated content. Our blog post summarizes the study on the viability of Mitra devices for remote TDM, highlighting the device's potential for immunosuppressant monitoring. Read the original study poster for details.

For more information about the work of researchers at LabExperts, please visit their laboratory web page, featured here on our Neoteryx website.

Image Credits: Trajan, Neoteryx