Highly sensitive quantification of pemetrexed in human plasma using UPLC‐MS/MS to support microdosing studies. (22nd November 2021)

• Record Type: Journal Article
• Authors: van Ewijk‐Beneken Kolmer, Eleonora W. J.; Teulen, Marga J. A.; Boosman, Rene J.; de Rouw, Nikki; Burgers, Jacobus A.; ter Heine, Rob
• Is Part Of: Biomedical chromatography. Volume 36:Number 2(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-11-22
• Subjects: microdosing -- pemetrexed -- plasma -- tandem mass spectrometry -- ultra‐high performance liquid chromatography; Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.5277
• Languages: English
• ISSNs: 0269-3879

Abstract

Abstract: 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 C5 ]‐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.