التفاصيل البيبلوغرافية
| العنوان: |
A Sensitive Assay for Unbound Docetaxel Using Ultrafiltration plus HPLC-MS and Its Application to a Clinical Study. |
| المؤلفون: |
Wang, David, Hughes-Medlicott, Natalie, Klingler, Lilian, Wang, Yi, Hung, Noelyn, Duffull, Stephen, Hung, Tak, Glue, Paul, Qin, Albert, Kwan, Rudolf, Chan, Wing-Kai, Jackson, Christopher |
| المصدر: |
Pharmaceutics; May2024, Vol. 16 Issue 5, p602, 10p |
| مصطلحات موضوعية: |
DOCETAXEL, LIQUID chromatography-mass spectrometry, ORAL drug administration, ULTRAFILTRATION, HIGH performance liquid chromatography, TANDEM mass spectrometry |
| الشركة/الكيان: |
UNITED States. Food & Drug Administration |
| مستخلص: |
Introduction: Docetaxel, a taxane used in the treatment of solid tumours, exerts pharmacological activity when in its unbound form. We report a sensitive assay to quantify unbound docetaxel after oral administration of docetaxel plus encequidar (oDox+E). Unbound drug quantification is important due to its direct correlation with drug-related toxicity and therapeutic efficacy. We improve on the sensitivity of current assay methods and demonstrate the utility of the assay on a novel formulation of oral docetaxel. Methods: Ultrafiltration followed by high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS) was utilized. Long-term stability, precision, accuracy, and recovery experiments were conducted to validate the assay. Additionally, patient samples from a Phase I dose-escalation pharmacokinetic study were analyzed using the developed assay. Results: The assay method exhibited long-term stability with an observed change between 0.8 and 6.9% after 131 days of storage at −60 °C. Precision and accuracy quality controls met the FDA acceptance criteria. An average recovery of 88% was obtained. Patient sample analysis demonstrated successful implementation of the assay. Conclusion: A validated sensitive assay was developed with an LLOQ of 0.084 ng/mL using 485 µL of human plasma. The sensitivity of the assay allowed quantification of unbound docetaxel concentrations in an early-phase oDox+E clinical study to compare it against IV docetaxel using pharmacokinetic modelling. Successful development of oDox+E represents an opportunity to replace the current IV docetaxel regimen with an oral regimen with lower cost, decreased side effects, and improve patient quality of life and experience. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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