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Related Concept Videos

Therapeutic Drug Monitoring: Drug Analysis Methods01:26

Therapeutic Drug Monitoring: Drug Analysis Methods

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Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood or body tissues to tailor drug therapy effectively. This monitoring is critical for managing drugs with narrow therapeutic indices like digoxin and phenytoin, ensuring they are both safe and effective. For instance, monitoring theophylline levels in asthma patients involves precision and sensitivity to adjust doses according to individual responses to therapy, ensuring efficacy and...
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Related Experiment Video

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Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
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A Sensitive Assay for Unbound Docetaxel Using Ultrafiltration plus HPLC-MS and Its Application to a Clinical Study.

David Wang1, Natalie Hughes-Medlicott2, Lilian Klingler3

  • 1Department of Anaesthesia, Waikato Hospital, Hamilton 3204, New Zealand.

Pharmaceutics
|May 25, 2024
PubMed
Summary

A new sensitive assay accurately measures unbound docetaxel in plasma. This supports the development of oral docetaxel plus encequidar (oDox+E) for improved cancer treatment.

Keywords:
clinical trialdocetaxelunbound assay

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Area of Science:

  • Pharmacology
  • Analytical Chemistry
  • Oncology

Background:

  • Docetaxel, a crucial taxane for solid tumors, is pharmacologically active in its unbound form.
  • Quantifying unbound docetaxel is vital for assessing drug toxicity and therapeutic effectiveness.
  • Current assay methods require improved sensitivity for unbound drug measurement.

Purpose of the Study:

  • To develop and validate a highly sensitive assay for quantifying unbound docetaxel.
  • To assess the utility of this assay in analyzing patient samples from an oral docetaxel plus encequidar (oDox+E) pharmacokinetic study.
  • To support the clinical development of an oral docetaxel formulation.

Main Methods:

  • Ultrafiltration coupled with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).
  • Assay validation included long-term stability, precision, accuracy, and recovery assessments.
  • Analysis of patient plasma samples from a Phase I pharmacokinetic study.

Main Results:

  • The developed assay demonstrated excellent long-term stability (0.8–6.9% change over 131 days at -60 °C).
  • Assay precision and accuracy met FDA acceptance criteria, with an average recovery of 88%.
  • Successful quantification of unbound docetaxel in patient samples confirmed assay applicability.

Conclusions:

  • A validated, sensitive assay with a 0.084 ng/mL lower limit of quantification (LLOQ) was established for human plasma.
  • The assay's sensitivity enables pharmacokinetic modeling to compare oral docetaxel plus encequidar (oDox+E) with intravenous docetaxel.
  • The successful development of oDox+E offers a potential oral alternative to IV docetaxel, promising reduced costs, fewer side effects, and enhanced patient quality of life.