Simultaneous analysis of docetaxel and the formulation vehicle polysorbate 80 in human plasma by liquid chromatography/tandem mass spectrometry.
An analytical procedure for the simultaneous determination of the anticancer agent docetaxel (Taxotere) and its formulation vehicle polysorbate 80 (Tween 80) in human plasma samples is described. Sample pretreatment involved a double liquid-liquid extraction step with a mixture of acetonitrile/n-butyl chloride (1/4, v/v). Separation of the compounds of interest, including the internal standard paclitaxel, was achieved on a reversed-phase Waters X-Terra mass spectrometry (MS) column (50 x 2.1mm internal diameter) packed with a 3.5-microm octadecyl stationary phase, using isocratic elution. Detection of docetaxel and polysorbate 80 was performed using tandem MS detection with electrospray ionization. Validation results indicated that the method is accurate and precise and has lower limits of quantitation of 0.500 nM (approximately 0.4 ng/ml) and 1.00 microg/ml for docetaxel and polysorbate 80, respectively. The method was subsequently used to measure concentrations of docetaxel and polysorbate 80 in plasma samples in support of a project to assess the influence of polysorbate 80 concentrations on the disposition and toxicity profile of docetaxel in cancer patients receiving Taxotere.
Baker
Sharyn D
SD
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA. sdbaker@jhmi.edu
Zhao
Ming
M
He
Ping
P
Carducci
Michael A
MA
Verweij
Jaap
J
Sparreboom
Alex
A
D002851:Chromatography, High Pressure Liquid; D000077143:Docetaxel; D004337:Drug Carriers / Q000032:analysis* / Q000493:pharmacokinetics; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry; D011136:Polysorbates / Q000032:analysis* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D043823:Taxoids / Q000097:blood*
D004337:Drug Carriers; D011136:Polysorbates; D043823:Taxoids; D000077143:Docetaxel