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A new ultrafast and high-throughput mass spectrometric approach for the therapeutic drug monitoring of the multi-targeted anti-folate pemetrexed in plasma from lung cancer patients
Authors:Roland J. W. Meesters  Robin Cornelissen  Rob J. van Klaveren  Robert de Jonge  Ethan den Boer  Jan Lindemans  Theo M. Luider
Affiliation:1. Department of Neurology, Laboratory of Neuro-Oncology and Clinical & Cancer Proteomics, University Medical Center Rotterdam (ErasmusMC), Dr. Molewaterplein 50, Room Ee-1981, 3015 GE, Rotterdam, The Netherlands
2. Department of Pulmonology, University Medical Center Rotterdam (Erasmus MC—Daniel Den Hoed Cancer Center), ’s Gravendijkwal 230, 3015 CD, Rotterdam, The Netherlands
3. Department of Clinical Chemistry, University Medical Center Rotterdam (Erasmus MC), ’s Gravendijkwal 230, 3015 CD, Rotterdam, The Netherlands
Abstract:An analytical assay has been developed and validated for ultrafast and high-throughput mass spectrometric determination of pemetrexed concentrations in plasma using matrix assisted laser desorption/ionization–triple quadrupole–tandem mass spectrometry. Patient plasma samples spiked with the internal standard methotrexate were measured by multiple reaction monitoring. The detection limit was 0.4 fmol/μL, lower limit of quantification was 0.9 fmol/μL, and upper limit of quantification was 60 fmol/μL, respectively. Overall observed pemetrexed concentrations in patient samples ranged between 8.7 (1.4) and 142.7 (20.3)?pmol/μL (SD). The newly developed mass spectrometric assay is applicable for (routine) therapeutic drug monitoring of pemetrexed concentrations in plasma from non-small cell lung cancer patients.
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