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A simple and fast LC-MS/MS method with a very high sensitivity for the measurement of raltitrexed in human plasma.
Kim, Stefano; Bisch, Amaëlle; Montange, Damien; Paillard, Marie-Justine; Nguyen, Thierry; Jary, Marine; Jacquin, Marion; Winkfield, Betsy; Borg, Christophe; Royer, Bernard.
Afiliación
  • Kim S; CHU Besançon, Department of Medical Oncology, F-25030 Besançon Cedex, France; INSERM, Unit 1098, University of Bourgogne Franche-Comté, F-25020 Besançon, France; CHU Besançon, Clinical Investigational Center CIC-1431, F-25030 Besançon Cedex, France. Electronic address: chkim@chu-besancon.fr.
  • Bisch A; CHU Besançon, Department of Pharmacology and Toxicology, F-25030 Besançon Cedex, France. Electronic address: abisch@chu-besancon.fr.
  • Montange D; CHU Besançon, Department of Pharmacology and Toxicology, F-25030 Besançon Cedex, France. Electronic address: dmontange@chu-besancon.fr.
  • Paillard MJ; CHU Besançon, Department of Medical Oncology, F-25030 Besançon Cedex, France; CHU Besançon, Methodology and Quality of Life in Oncology Unit, F-25030 Besançon Cedex, France. Electronic address: mariejustine.paillard@gmail.com.
  • Nguyen T; CHU Besançon, Department of Medical Oncology, F-25030 Besançon Cedex, France. Electronic address: tnguyentanhon@chu-besancon.fr.
  • Jary M; CHU Besançon, Department of Medical Oncology, F-25030 Besançon Cedex, France; INSERM, Unit 1098, University of Bourgogne Franche-Comté, F-25020 Besançon, France; CHU Besançon, Clinical Investigational Center CIC-1431, F-25030 Besançon Cedex, France. Electronic address: mjary@chu-besancon.fr.
  • Jacquin M; CHU Besançon, Clinical Investigational Center CIC-1431, F-25030 Besançon Cedex, France; Cancéropôle Grand Est, France. Electronic address: m1jacquin@chu-besancon.fr.
  • Winkfield B; Nord Franche-Comté Hospital, Department of Gastroenterology, F-90000 Belfort, France. Electronic address: betsy.winkfield@hnfc.fr.
  • Borg C; CHU Besançon, Department of Medical Oncology, F-25030 Besançon Cedex, France; INSERM, Unit 1098, University of Bourgogne Franche-Comté, F-25020 Besançon, France; CHU Besançon, Clinical Investigational Center CIC-1431, F-25030 Besançon Cedex, France. Electronic address: christophe.borg@efs.sante.fr.
  • Royer B; INSERM, Unit 1098, University of Bourgogne Franche-Comté, F-25020 Besançon, France; CHU Besançon, Department of Pharmacology and Toxicology, F-25030 Besançon Cedex, France. Electronic address: broyer@chu.besancon.fr.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1060: 240-246, 2017 Aug 15.
Article en En | MEDLINE | ID: mdl-28628839
Raltitrexed is a thymidylate synthase inhibitor that can be administered safely to patients with cardiovascular disease or dihydropyrimidine dehydrogenase deficiency, as opposed to 5FU. The recommended dose of 3mg/m2 every 3 weeks often leads to toxicity. Interestingly, the 2mg/m2 every 2 weeks dose appears to be less toxic. A pharmacokinetic trial was then performed by our team to investigate such phenomenon. However, there are currently, two main methods for RTX measurement described in the literature: a radioimmunoassay (RIA) and chromatographic-based methods with either UV or mass spectrometry detections. The RIA methods: display a low limit of quantification (below 1µg/L), but also a low extent of linearity for the calibration curve. The chromatographic-based methods: include high level of calibrators, but have poor sensitivity (>2µg/mL). If a high sensitivity is essential to satisfactorily describe the elimination of RTX, high concentrations in the calibration curve are also needed to avoid bias linked to the dilutions of the samples. A new LC-MS/MS method was then developed that allows to simultaneously measure very low (0.1µg/L) and very high (3000µg/L) concentrations in the same run. Moreover, the extraction steps are very simple and fast with mainly a precipitation and a filtration steps. This method was validated following the EMA recommendations. In view of the extent of the calibration curve, the carry-over effect was more deeply investigated. With this method, it was possible to measure RTX in samples taken 3 weeks after the administration. Taken together, this method allows to simply and quickly measure RTX in plasma of patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quinazolinas / Tiofenos / Cromatografía Liquida / Espectrometría de Masas en Tándem Tipo de estudio: Clinical_trials / Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: J Chromatogr B Analyt Technol Biomed Life Sci Asunto de la revista: ENGENHARIA BIOMEDICA Año: 2017 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quinazolinas / Tiofenos / Cromatografía Liquida / Espectrometría de Masas en Tándem Tipo de estudio: Clinical_trials / Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: J Chromatogr B Analyt Technol Biomed Life Sci Asunto de la revista: ENGENHARIA BIOMEDICA Año: 2017 Tipo del documento: Article Pais de publicación: Países Bajos