Quantification of docetaxel and its metabolites in human plasma by liquid chromatography/tandem mass spectrometry.

Article Details

Citation
Copy to clipboard

Hendrikx JJ, Dubbelman AC, Rosing H, Schinkel AH, Schellens JH, Beijnen JH

Quantification of docetaxel and its metabolites in human plasma by liquid chromatography/tandem mass spectrometry.

Rapid Commun Mass Spectrom. 2013 Sep 15;27(17):1925-34. doi: 10.1002/rcm.6654.

PubMed ID
23939959 [ View in PubMed
]
Abstract

RATIONALE: During drug development accurate quantification of metabolites in biological samples using mass spectrometry is often hampered by the lack of metabolites of chemically pure quality. However, quantification of metabolites can be useful for assessment and interpretation of (pre)clinical data. We now describe an approach to quantify docetaxel metabolites in human plasma by liquid chromatography/tandem mass spectrometry (LC/MS/MS) using docetaxel calibration standards. METHODS: Metabolites (M1/M3, M2 and M4) were generated using microsomal incubations. Retention times of docetaxel and its metabolites were assessed using an LC/UV assay and peak identification was performed by LC/MS(n). Samples containing isolated metabolites from human faeces were quantified by LC/UV and used as references for spiking human plasma samples. LC/MS/MS was applied to sensitively quantify docetaxel and its metabolites in human plasma using docetaxel calibration standards in a range of 0.25-500 ng/mL. RESULTS: Because ionisation of docetaxel and its metabolites differed, correction factors were established to quantify the metabolites using docetaxel calibration samples. During method validation, accuracy and precision of the metabolites were within +/-7.7% and

DrugBank Data that Cites this Article

Drugs