title: Sensitive liquid chromatography-mass spectrometry assay for quantitation of docetaxel and paclitaxel in human plasma.
abstract: We have developed a high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-MS) method for quantifying docetaxel and paclitaxel in human plasma. The assay fulfills the need for defining the lower plasma concentrations of these antineoplastic agents that result from a number of changes in how these agents are used clinically. The assay uses paclitaxel as the internal standard for docetaxel, and vice versa; solid-phase extraction; a Phenomenex Hypersil ODS (5 micrometer, 100x2 mm) reversed-phase analytical column; an isocratic mobile phase of 0.1% formic acid in methanol-water (70:30, v/v); and mass spectrometric detection using electrospray positive mode electron ionization. The assay has a lower limit of quantitation (LLOQ) of 0.3 nM and is linear between 0.3 nM and 1 microM for docetaxel. For paclitaxel, the LLOQ was 1 nM, and the assay is linear between 1 nM and 1 microM. We demonstrated the suitability of this assay for docetaxel by using it to quantify the docetaxel concentrations in plasma of a patient given 40 mg/m(2) of docetaxel and comparing those results to results produced when the same samples were assayed with an HPLC assay using absorbance detection. In a similar manner, the suitability of the assay for paclitaxel was demonstrated by using it to quantify the concentrations of paclitaxel in the plasma of a patient given 15 mg/m(2) of paclitaxel and comparing those results to results produced when the same samples were assayed with an HPLC assay using absorbance detection. The LC-MS assay, which proved superior because of its greater sensitivity and relatively short (7 min) run time, should be an important tool for future pharmacokinetic analyses of docetaxel and paclitaxel.
authors.affiliation: Program of Molecular Therapeutics and Drug Discovery, University of Pittsburgh Cancer Institute, 15213, Pittsburgh, PA, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Parise
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.forename: William C
authors.initials: WC
authors.lastname: Zamboni
authors.forename: Merrill J
authors.initials: MJ
authors.lastname: Egorin
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D000077143:Docetaxel; D006801:Humans; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000097:blood*; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D043823:Taxoids
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel