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.
Highlights
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
Analytical methods using ultrafiltration followed by HPLC-MS/MS were reported for determining unbound docetaxel in biological samples[2,14]
These results showed that liposome carriers led to a significant difference in tissue distributions and PK profiles compared to a traditional docetaxel injection[19]
Summary
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. The methods were validated to show the standard range linearity, sensitivity, selectivity, accuracy, precision, and stability of docetaxel in the matrices tested This method is fast and simple with a short run time of 4.5 min and a small plasma sample volume (500 μL). Several factors contributed to the complexity of the pharmacologic effects of the drug delivered by carriers after iv administration, including that the circulating drug was present in three different forms (e.g., protein-unbound, protein-bound, and carrier-associated) Because these pools differed in their PKs, efficacy, and safety, quantification of the total drug concentration alone was insufficient to characterize the biopharmaceutic properties of drugs loaded or encapsulated in carriers. The authors present the development and validation of a versatile and sensitive UPLC-MS/MS method to determine unbound and total docetaxel in plasma with the advantages of a short run time and small plasma sample volume. These data were used to estimate the docetaxel concentrations of plasma in various pools (e.g., unbound, protein-bound, and micellar-associated) after administration of docetaxel micelles
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
