title: Simultaneous online SPE-HPLC-MS/MS analysis of docetaxel, temsirolimus and sirolimus in whole blood and human plasma.
abstract: Docetaxel and temsirolimus are some of the most used drugs in a wide range of solid tumors. In preclinical studies, mTOR inhibitors such as temsirolimus have demonstrated synergistic cytotoxic effects with taxanes providing the rationale for combination studies. These anticancer agents exhibit a narrow therapeutic concentration range and due to their high inter- and intra-individual pharmacokinetic variability, therapeutic dose monitoring by highly sensitive methods as LC-MS/MS are important for clinical research. Therefore, the aim of this study was to develop and validate a sensitive, fast and convenient method for the simultaneous identification and quantification of docetaxel, temsirolimus and its main metabolite, sirolimus, using paclitaxel, another anticancer drug, as the internal standard. These analytes were quantified by an integrated online solid phase extraction-high performance liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS) system. Separation was performed on a Zorbax eclipse XDB-C8 (150mm×4.6mm, 5μm) column. The mass spectrometer tandem quadruple detector was equipped with jet stream electrospray ionization, monitored in multiple reactions monitoring (MRM) and operated in positive mode. A combination of protein precipitation with methanol/zinc sulphate (70:30) (v/v) and online SPE using a Zorbax eclipse plus C8 (12.5mm×4.6mm, 5μm) cartridge was used to extract the compounds. This method allows the use of the same reagents, sample treatment and analytical technique independently of whether the samples are whole blood or plasma. The method has been successfully validated and applied to real samples. It is a suitable method for dose adjustment and for evaluating potential drug interactions during combined treatments.
authors: CEMBIO (Center for Metabolomics and Bioanalysis), Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe, Boadilla del Monte, 28668 Madrid, Spain.
authors: Alicia
authors: A
authors: Navarrete
authors: M Paz
authors: MP
authors: Martínez-Alcázar
authors: Ignacio
authors: I
authors: Durán
authors: Emiliano
authors: E
authors: Calvo
authors: Belén
authors: B
authors: Valenzuela
authors: Coral
authors: C
authors: Barbas
authors: Antonia
authors: A
authors: García
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D000077143:Docetaxel; D006801:Humans; D012680:Sensitivity and Specificity; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000097:blood*; D052616:Solid Phase Extraction / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D043823:Taxoids / Q000097:blood*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; C401859:temsirolimus; D020123:Sirolimus