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Therapeutic Drug Monitoring of Everolimus Using Volumetric Absorptive Microsampling and Quantitative Dried Blood Spot Methods with LC-MS/MS in Adult Solid Organ Transplant Recipients: An Analytical and Clinical Comparative Study.

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  • معلومة اضافية
    • المصدر:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Basel, Switzerland : MDPI, c1995-
    • الموضوع:
      Everolimus*/blood ; Everolimus*/therapeutic use ; Everolimus*/pharmacokinetics ; Drug Monitoring*/methods ; Tandem Mass Spectrometry*/methods ; Dried Blood Spot Testing*/methods ; Organ Transplantation* ; Immunosuppressive Agents*/blood ; Immunosuppressive Agents*/therapeutic use ; Immunosuppressive Agents*/pharmacokinetics; Humans ; Chromatography, Liquid/methods ; Adult ; Middle Aged ; Male ; Female ; Transplant Recipients ; Reproducibility of Results ; Liquid Chromatography-Mass Spectrometry
    • نبذة مختصرة :
      Everolimus (EVE), an mTOR inhibitor, is widely used in solid organ transplantation (SOT) because of its immunosuppressive properties. Due to its narrow therapeutic window and significant pharmacokinetic variability, therapeutic drug monitoring (TDM) is essential for achieving optimal outcomes. We developed and thoroughly validated a robust LC-MS/MS method to measure EVE levels in venous whole blood (WB) and capillary blood collected using two microsampling devices: Mitra™ (volumetric absorptive microsampling, VAMS) and Capitainer ® (quantitative dried blood spot, qDBS). The validation followed EMA and IATDMCT guidelines, assessing linearity (1.27-64.80 ng/mL for WB and 0.50-60 ng/mL for VAMS/qDBS), as well as selectivity, accuracy, precision, matrix effects, recovery, stability, and incurred sample reanalysis. Clinical validation involved 66 matched samples from 33 adult SOT recipients. The method demonstrated high accuracy and precision across all matrices, with no significant carryover or matrix interference. Statistical analysis using Passing-Bablok regression and Bland-Altman plots showed excellent agreement between the microsampling methods and the venous reference. Hematocrit effects were tested both in laboratory conditions and on clinical samples and were found to be negligible. This study provides the first comprehensive analytical and clinical validation of the Mitra and Capitainer devices for EVE monitoring. The validated LC-MS/MS microsampling method supports decentralized, patient-centred TDM, offering a reliable alternative to conventional blood sampling in transplant care.
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    • Grant Information:
      1/F/MB/N/24 Medical University of Warsaw
    • Contributed Indexing:
      Keywords: LC-MS/MS; VAMS; everolimus; qDBS; solid organ transplantation
    • الرقم المعرف:
      9HW64Q8G6G (Everolimus)
      0 (Immunosuppressive Agents)
    • الموضوع:
      Date Created: 20250814 Date Completed: 20250826 Latest Revision: 20250826
    • الموضوع:
      20250903
    • الرقم المعرف:
      PMC12348445
    • الرقم المعرف:
      10.3390/molecules30153139
    • الرقم المعرف:
      40807312