School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 11031, Taiwan.
Sci Rep. 2017 Nov 6;7(1):14609. doi: 10.1038/s41598-017-15176-0.
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 0.10810.8 and 0.54216 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.
建立并验证了一种灵敏且特异的液相色谱/串联质谱（LC-MS/MS）法，用于定量测定血浆中总游离和结合型多西他赛的药物浓度。游离和总多西他赛的校准曲线在各自的 0.10810.8 和 0.54216 ng/mL 范围内呈线性。日内和日间测定的准确度和精密度均不超过 15%。该方法经过验证，可显示在测试基质中多西他赛的标准范围线性、灵敏度、选择性、准确度、精密度和稳定性。此外，该方法快速简便，运行时间仅为 4.5 分钟，且所需的血浆样本量较小（500 μL）。该方法已成功应用于大鼠静脉注射 10 mg/kg 多西他赛胶束制剂后的药代动力学研究。多西他赛胶束缓慢释放其药物载量，同时存在结合型、游离型和胶束型药物池。在该研究中还测量了这些不同形式的血浆池。我们证实，多西他赛胶束给药后，大多数多西他赛（24 h 时为 96.52%，72 h 时为 83.14%）与胶束相关，这是由于药物被长循环胶束隔离。
