Highly sensitive quantification of pemetrexed in human plasma using UPLC-MS/MS to support microdosing studies.

Autor: van Ewijk-Beneken Kolmer EWJ; Department of Pharmacy and Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Teulen MJA; Department of Pharmacy and Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Boosman RJ; Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek-The Netherlands Cancer Institute, Amsterdam, The Netherlands., de Rouw N; Department of Pharmacy and Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Pharmacy, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands., Burgers JA; Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek-The Netherlands Cancer Institute, Amsterdam, The Netherlands., Ter Heine R; Department of Pharmacy and Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Jazyk: angličtina
Zdroj: Biomedical chromatography : BMC [Biomed Chromatogr] 2022 Feb; Vol. 36 (2), pp. e5277. Date of Electronic Publication: 2021 Nov 22.
DOI: 10.1002/bmc.5277
Abstrakt: Pemetrexed is an antifolate drug approved for the treatment of non-small-cell lung cancer and mesothelioma. Assessing pemetrexed pharmacokinetics after administration of a microdose (100 μg) may facilitate drug-drug interaction and dose individualization studies with cytotoxic drugs, without causing harm to patients. Therefore, a highly sensitive bioanalytical assay is required. A reversed-phase ultra-high performance liquid chromatography method was developed to determine pemetrexed concentrations in human ethylenediaminetetraacetic acid-plasma after microdosing. [ 13 C 5 ]-Pemetrexed was used as the internal standard. The sample preparation involved solid-phase extraction from plasma. Detection was performed using MS/MS in a total run time of 9.5 min. The assay was validated over the concentration range of 0.0250-25.0 μg/L pemetrexed. The average accuracies for the assay in plasma were 96.5 and 96.5%, and the within-day and between-day precision in coefficients of variations was <8.8%. Extraction recovery was 59 ± 1 and 55 ± 5% for pemetrexed and its internal standard. Processed plasma samples were stable for 2 days in a cooled autosampler at 10°C. The assay was successfully applied in a pharmacokinetic curve, which was obtained as a part of an ongoing clinical microdosing study.
(© 2021 The Authors. Biomedical Chromatography published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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