Development of a new method for the quantitation of metabolites in the absence of chemically synthetized authentic standards.
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Altares R, Marquez Del Pino FM, Benedit G, Guillen MJ, Cuevas C, Perez de la Cruz MA, Aviles P
Development of a new method for the quantitation of metabolites in the absence of chemically synthetized authentic standards.
J Pharm Biomed Anal. 2019 May 30;169:70-74. doi: 10.1016/j.jpba.2019.01.027. Epub 2019 Feb 21.
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- 30831452 [ View in PubMed]
- Abstract
A new method for the quantification of metabolites in the absence of a chemically synthetized authentic standard is described herein. Metabolites to be used as reference standards were obtained biologically from microsomes incubation. The method is a stepwise process in which, only the radiolabeled ((14)C) and non-radiolabeled parent compound are required. Briefly, the separation and principles of equimolar detection of LC-radioactivity were applied and, a calibration curve of the (14)C-parent compound was used to quantify the formation of its (14)C-metabolite. In turn, serial dilutions of this (14)C-metabolite were the base for the calibration curve that allowed the quantification of the non-radiolabeled metabolite. This method was applied in plasma samples obtained from a dog pharmacokinetic study in which, a PharmaMar compound (lurbinectedin) and its N-desmethylated metabolite were quantified and, the results compared to those obtained by the classical approach (with the chemically synthetized N-desmethylated metabolite). Plasma concentrations obtained with the two methods were very similar, with standard relative errors between -11% to -4%. Similar, main pharmacokinetic parameters were calculated with the concentrations obtained either thru this method or by using a chemically synthetized authentic standard.
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