Determination of docetaxel in dried blood spots by LC-MS/MS: Method development, validation and clinical application.
In this study, a LC-MS/MS method for the measurement of docetaxel in Dried Blood Spots (DBS) samples was developed and validated. Docetaxel was extracted from 8 mm DBS punch with a mixture of methanol and acetonitrile (9:1, v/v). The chromatographic separation occurred in an Acquity® C18 column (150 × 2.1 mm, 1.7 μm) eluted with a mixture of water and acetonitrile plus 0.1% formic acid (45:55, v/v). Total analytical run time was 7 min. The method was linear from 50 to 3000 ng ml-1. Precision assays showed CV% < 9.8% and accuracy between 99 and 103%, mean recovery was 81%. The method was applied in the determination of the docetaxel in 31 patients, after collection of two paired venous blood and DBS samples, following a limited sampling strategy protocol. The analyte was stable in DBS for 18 days at 25 °C and 9 days at 45 °C. The interval of docetaxel concentrations measured in DBS collected before the end of the infusion was 756-3047 ng ml-1 and 60 ± 10 min after the end of the infusion was 57-331 ng ml-1. AUC values calculated from DBS-derived estimated plasma concentrations (EPC) represented on average 100% of those obtained in plasma samples of 3.1 mgh/l (2.4-4.9 mg h/l). There was a 93% agreement between the classification of patients as within or without the therapeutic range by plasma and EPC AUC. These findings support the clinical use of DBS sampling for routine therapeutic drug monitoring of docetaxel.
['Raymundo|S|S|', 'Muller|V V|VV|', 'Andriguetti|N B|NB|', 'Tegner|M|M|', 'Artmann|A C|AC|', 'Kluck|H M|HM|', 'Franzoi|M A|MA|', 'Vilela|R M M|RMM|', 'Schwartsmann|G|G|', 'Linden|R|R|', 'Antunes|M V|MV|']
D002853:Chromatography, Liquid D000077143:Docetaxel D059788:Dried Blood Spot Testing D016903:Drug Monitoring D006801:Humans D015203:Reproducibility of Results D053719:Tandem Mass Spectrometry D043823:Taxoids
Docetaxel Dried blood spots Therapeutic drug monitoring LC–MS/MS