Comparison of conventional dried blood spots and volumetric absorptive microsampling for tacrolimus and mycophenolic acid determination

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 208; p. 114443
• Main Authors: Paniagua-González, Lucía, Lendoiro, Elena, Otero-Antón, Esteban, López-Rivadulla, Manuel, de-Castro-Ríos, Ana, Cruz, Angelines
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 20-01-2022
• Subjects: Blood Specimen Collection; Dried Blood Spot Testing; Dried blood spots (DBS); Humans; Immunosuppressive Agents; Mycophenolic Acid; Sampling quality; Tacrolimus; Therapeutic drug monitoring; Volumetric absorptive microsampling (VAMS); Therapeutic drug monitoring; Dried blood spots (DBS); Volumetric absorptive microsampling (VAMS); Sampling quality; Mycophenolic acid; Tacrolimus
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2021.114443

Therapeutic drug monitoring (TDM) of immunosuppressants is essential to avoid either rejection or toxicity after solid organ transplantations. Capillary microsampling approaches are an outstanding alternative to conventional venous sampling for TDM (easy and non-invasive collection, enabling self-sampling, and cost-saving shipment, processing and storage). Volumetric absorptive microsampling (VAMS) has gained importance in the last years, as it was meant to overcome the hematocrit (Hct) related issues commonly associated to DBS analysis. Despite all the benefits, microsampling techniques performance (including a thorough clinical validation) should be set up before their implementation in clinical practice. The aim of this study was to perform a clinical validation for both tacrolimus (TAC) and mycophenolic acid (MPA) in both DBS and Mitra™ VAMS. For the clinical validations, two different requirements were set up: analytical (following EMA and FDA guidelines) and clinical (following the Royal College of Pathologists of Australasia -RCPA- recommendations) acceptance criteria. For DBS, both analytical and clinical acceptance criteria were fulfilled for TAC, with 98.7% and 95% of the paired samples within the preset limits, respectively. For MPA, the analytical criterion was met (70.6% of paired specimens), although only half of the pairs were within the clinical limits. For VAMS, the clinical validation for both TAC and MPA showed good correlations but significant lower concentrations in VAMS compared to the routine matrices. After VAMS concentrations correction, the analytical requirement was fulfilled for both analytes (71.1% for TAC, 75% for MPA), although the more restrictive criteria recommended by the RCPA were not met for any analyte (half of the samples fell within the acceptance area). In addition, no significant Hct impact on the quantification was found in any case. Also, a preliminary home-sampling trial was set up, showing promising results. Moreover, a comparison between VAMS vs. DBS analytical and clinical performances was carried out, including a home-sampling trial, sample quality results and costs. Although the analytical performance for both VAMS and DBS was similar, DBS were superior regarding clinical criteria, sampling quality and cost.
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•Tacrolimus and mycophenolic acid were clinically validated in DBS and VAMS.•Capillary samples vs. routine matrices showed good correlations in all cases.•VAMS vs. DBS analytical and clinical performances comparison was carried out.•A preliminary home-sampling trial was set up, showing promising results.•DBS were superior to VAMS regarding clinical criteria, sampling quality and cost.