A new quantification method for assessing plasma concentrations of pemetrexed and its polyglutamate metabolites
Autor: | Theo M. Luider, Sabine Visser, Marcel P. Stoop, Bruno H. Stricker, Evert van Dijk, Joachim G.J.V. Aerts |
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Přispěvatelé: | Neurology, Pulmonary Medicine, Epidemiology |
Rok vydání: | 2016 |
Předmět: |
Male
Analyte Lung Neoplasms Clinical Biochemistry Pharmaceutical Science Context (language use) Pemetrexed Pharmacology Tandem mass spectrometry Mass spectrometry 030226 pharmacology & pharmacy 01 natural sciences Analytical Chemistry Plasma 03 medical and health sciences 0302 clinical medicine Glutamates Tandem Mass Spectrometry Carcinoma Non-Small-Cell Lung Drug Discovery medicine Humans Spectroscopy Aged Reproducibility Chromatography Polyglutamate medicine.diagnostic_test Chemistry 010401 analytical chemistry Reproducibility of Results Middle Aged 0104 chemical sciences Polyglutamic Acid Therapeutic drug monitoring Drug Monitoring Chromatography Liquid medicine.drug |
Zdroj: | Journal of Pharmaceutical and Biomedical Analysis, 128, 1-8. Elsevier |
ISSN: | 0731-7085 |
Popis: | Currently no quantification method exists for potentially therapeutically relevant polyglutamate metabolites of the drug pemetrexed which is used for the treatment of lung carcinoma patients. We developed and tested an LC-MS/MS-based analytical assay that uses isotope-labeled internal standards to quantify pemetrexed and its (poly)glutamate metabolites in clinical human plasma samples of lung carcinoma patients. UHPLC chromatography and triple quadrupole mass spectrometry showed an LLOQ of 0.2nmol/L for pemetrexed and an LLOQ of 0.5nmol/L for the two metabolites (one glutamate and two glutamate moieties covalently bound to the pemetrexed molecule, for which no other quantification methods have previously been published). The recoveries for PMTX and its metabolites ranged between 30% and 67%. Precision and accuracy at a concentration of 20nmol/L for all four analytes was well below 15% CV. The precision (RSD) in the biological replicates of the separate days (within-run precision) as well as the reproducibility over several days (between-run precision), tested in the range of 5-250nmol/L, were all below 15%. Autosampler, benchtop and freeze-thaw cycle stability of the analytes was also demonstrated. To illustrate the new assay in a relevant biological context, concentrations of pemetrexed and the two metabolites were quantified in plasma samples of lung carcinoma patients treated with pemetrexed. The assay is straightforward, relatively easy to perform, and has potential for use in therapeutic drug monitoring in non-small cell lung carcinoma patients. |
Databáze: | OpenAIRE |
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