Abstract：
:A sensitive and specific liquid chromatographic/tandem mass spectrometric (LC-MS/MS) method was developed and validated for quantifying total and unbound docetaxel drug concentrations in plasma. Calibration curves for unbound and total docetaxel were linear over the respective ranges of 0.108~10.8 and 0.54~216 ng/mL. The intra- and interday assay accuracy and precision did not exceed 15%. The methods were validated to show the standard range linearity, sensitivity, selectivity, accuracy, precision, and stability of docetaxel in the matrices tested. In addition, this method is fast and simple with a short run time of 4.5 min and a small plasma sample volume (500 µL). The validated method was successfully applied to a pharmacokinetic study of a docetaxel micelle formulation in rat plasma after intravenous administration at a dose of 10 mg/kg. Docetaxel micelles slowly released their drug payload, and protein-bound, unbound, and micellar drug pools existed simultaneously. These various forms in plasma pools were also measured in the study. We confirmed that most of the docetaxel in plasma was micelle-associated (96.52% at 24 h and 83.14% at 72 h) after micellar docetaxel administration, as a result of sequestration of the drug in long-circulating micelles.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Sheu MT,Wu CY,Su CY,Ho HOdoi
10.1038/s41598-017-15176-0subject
Has Abstractpub_date
2017-11-06 00:00:00pages
14609issue
1issn
2045-2322pii
10.1038/s41598-017-15176-0journal_volume
7pub_type
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