Therapeutic drug monitoring of doxorubicin in paediatric oncology using capillary electrophoresis

Abstract

A method for the determination of doxorubicin and its main metabolite doxorubicinol in human plasma is described. Two different sample preparation procedures are applied depending on the expected concentration: To monitor the peak plasma levels, 10 microL of plasma are deproteinated with acetonitrile. After centrifugation, the supernatant is directly applied to the capillary by hydrodynamic injection. For the determination of lower amounts of doxorubicin and its main metabolite doxorubicinol 100 microL of plasma is extracted by liquid-/liquid extraction with chloroform. After evaporation of the organic phase, the sample is reconstituted in acetonitrile/water (95/5 v/v) and injected into the capillary by electrokinetic injection. Idarubicin serves as the internal standard. Laser-induced fluorescence detection with an Ar-ion laser emitting at 488 nm and a 520 nm cut-off filter is used for detection. The accuracy of the method was calculated to be 3.0% at higher concentrations and 15.0% at the limit of quantification. Reproducibility data are in accordance to the generally accepted criteria for bioanalytical methods. The limit of quantification is 2 microg/L, enabling us to monitor doxorubicin plasma levels for several days after application. Noninvasive blood sampling (from the fingertip) using heparinized capillaries was found to be a simple and convenient procedure and provides reproducible data. Initial results show high interindividual variability in doxorubicin peak plasma levels.

Spatiotemporal dynamics of doxorubicin elution from embolic beads within a microfluidic network

“…10 detectability by fluorescence spectroscopy, which has a limit of detection (LOD) of 2.0 μg/L [52].…”

Synthesis of a Covalent Epirubicin-(C3-amide)-Anti-HER2/neuImmunochemotherapeutic Utilizing a UV-Photoactivated Anthracycline Intermediate

“…Known epirubicin reference controls were applied to generate a linear curve and the formulation of a mathematical equation that was utilized to accurately calculate and epirubicin concentrations between 10 -9 and 10 -5 M (final concentration). Determination of the concentration of nonconjugated ''free'' epirubicin contained in covalent epirubicin immunochemotherapeutic preparations was established by chloroform extraction, [60][61][62] with the organic phase collected by pipette, evaporated to dryness under a stream of nitrogen gas, and the resulting residue dissolved in Tris buffered saline (TBS, 50 mM, pH 7.4) before quantitative analysis.…”

Capillary Electrophoresis with Laser-induced Fluorescence Detection for Application in Intracellular Investigation of Anthracyclines and Multidrug Resistance Proteins

“…A migration solution containing 30% (v/v) acetonitrile was used in a similar separation of DOX, IDA and DNR 39 using CE-LIF. Separations of DOX and DNR after extraction, were reported by Simeon et al 40 and Hempel et al 41 in the determination of anthracyclines in plasma and tumors. Similar work employing cyclodextrin (CD)-assisted MEKC on the separation of DOX and doxorubicinol was reported by Eder et al 42 It should be mentioned that the aforementioned CE methods used organic solvents, which are known to precipitate proteins in biological samples, either during separation or extraction.…”