2. Academic Validation
  3. Imatinib and norimatinib therapeutic monitoring using dried blood spots: Analytical and clinical validation, and performance comparison of volumetric collection devices

Imatinib and norimatinib therapeutic monitoring using dried blood spots: Analytical and clinical validation, and performance comparison of volumetric collection devices

  • J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Apr 1:1255:124526. doi: 10.1016/j.jchromb.2025.124526.
Marco Orleni 1,  Sara Gagno 2,  Eleonora Cecchin 3,  Marcella Montico 4,  Angela Buonadonna 5,  Arianna Fumagalli 5,  Michela Guardascione 5,  Fabio Puglisi 6,  Giuseppe Toffoli 2,  Bianca Posocco 7,  Erika Cecchin 2
Affiliations

Affiliations

  • 1 Experimental and Clinical Pharmacology Unit, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; Doctoral School in Pharmacological Sciences, University of Padua, 35131 Padova, Italy.
  • 2 Experimental and Clinical Pharmacology Unit, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy.
  • 3 Experimental and Clinical Pharmacology Unit, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy; Department of Medicine (DMED), University of Udine, Udine, Italy.
  • 4 Clinical Trial Office, CRO Aviano, National Cancer Institute, IRCSS, 33081 Aviano, Italy.
  • 5 Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy.
  • 6 Department of Medicine (DMED), University of Udine, Udine, Italy; Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy.
  • 7 Experimental and Clinical Pharmacology Unit, CRO Aviano, National Cancer Institute, IRCCS, 33081 Aviano, Italy. Electronic address: bposocco@cro.it.
PMID: 39985852 DOI: 10.1016/j.jchromb.2025.124526
Abstract

Therapeutic drug monitoring during imatinib treatment is recommended to optimize patient clinical outcomes. This study aimed to develop a novel LC-MS/MS method to quantitate imatinib and its active metabolite N-desmethyl-imatinib, in volumetric dried blood spots (DBS) using the HemaXis DB10 and Capitainer B devices. Chromatographic separation was achieved using an XTerra MS C18 column and detection occurred with a SCIEX 4000QTrap tandem mass spectrometer using electrospray positive-mode ionization. Analytical validation was successfully performed adhering to the latest guidelines. The assay was linear over the range 240-6000 ng/mL for imatinib and 48-1200 ng/mL for its metabolite, accurate (89 %-113 %) and precise (≤17 % imprecision) across a hematocrit range of 22-55 % for both devices. Recovery ranged from 84 % to 92 %, with no influence of matrix components. Stability was confirmed after at least 43 days in desiccator conditions (20 °C, ≤35 % humidity), and in conditions that mimed home-sampling. Clinical validation, conducted on 52 paired DBS and plasma samples from 28 patients, revealed that the DBS-to-plasma ratio can be used to convert DBS measurements into plasma concentrations. Bland-Altman and Passing-Bablok analyses indicated strong agreement between the estimated and actual plasma concentrations for both imatinib and its metabolite across both devices. The conversion method was further tested on an additional set of 25 to 31 samples, with 80 to 97 % of the samples falling within ±20 % difference. This study proved that DBS collected using either HemaXis DB10 or Capitainer B devices can be reliably implemented as an alternative to plasma for therapeutic drug monitoring during imatinib therapy.

Keywords

Capitainer B; Dried blood spot; HemaXis DB10; Imatinib; LC-MS/MS; Pharmacokinetics; Therapeutic drug monitoring.

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