New Microfluidic-Based Sampling Procedure for Overcoming the Hematocrit Problem Associated with Dried Blood Spot Analysis

Abstract

Hematocrit (Hct) is one of the most critical issues associated with the bioanalytical methods used for dried blood spot (DBS) sample analysis. Because Hct determines the viscosity of blood, it may affect the spreading of blood onto the filter paper. Hence, accurate quantitative data can only be obtained if the size of the paper filter extracted contains a fixed blood volume. We describe for the first time a microfluidic-based sampling procedure to enable accurate blood volume collection on commercially available DBS cards. The system allows the collection of a controlled volume of blood (e.g., 5 or 10 μL) within several seconds. Reproducibility of the sampling volume was examined in vivo on capillary blood by quantifying caffeine and paraxanthine on 5 different extracted DBS spots at two different time points and in vitro with a test compound, Mavoglurant, on 10 different spots at two Hct levels. Entire spots were extracted. In addition, the accuracy and precision (n = 3) data for the Mavoglurant quantitation in blood with Hct levels between 26% and 62% were evaluated. The interspot precision data were below 9.0%, which was equivalent to that of a manually spotted volume with a pipet. No Hct effect was observed in the quantitative results obtained for Hct levels from 26% to 62%. These data indicate that our microfluidic-based sampling procedure is accurate and precise and that the analysis of Mavoglurant is not affected by the Hct values. This provides a simple procedure for DBS sampling with a fixed volume of capillary blood, which could eliminate the recurrent Hct issue linked to DBS sample analysis.

Therapeutic drug monitoring of tacrolimus and mycophenolic acid in outpatient renal transplant recipients using a volumetric dried blood spot sampling device

“…This could possibly be explained if these patients showed a divergent blood viscosity due to extremely high or low haematocrit values, affecting the flow rate in the DBS device capillary. However, the applied DBS sampling device has been validated for haematocrit values ranging from 0.26 to 0.62 , while our patients showed values between 0.33 and 0.55. Therefore, it seems unlikely that these differences arose from haematocrit‐related issues.…”

Evaluation of Mutual Drug–Drug Interaction within Geneva Cocktail for Cytochrome P450 Phenotyping using Innovative Dried Blood Sampling Method

“…To simplify this process, new precise volume sampling techniques have been developed [14,32]. One of these techniques involving the use of a simple microfluidic-based device incorporating 10 ll channels and commercially available DBS cards has been tested in this study [14]. Probe and metabolite concentrations obtained using this sampling method coincided with those obtained using a volumetric micropipette.…”

Quantitative determination of opioids in whole blood using fully automated dried blood spot desorption coupled to on‐line SPE‐LC‐MS/MS

“…not only the effect on spot size but also on analyte recovery), the recovery of the whole spot assay must be high enough . Several promising approaches are currently being developed/tested to deal with these challenges and will be explored by the authors in future research …”