Abstract：
BACKGROUND: Aromatase inhibitors such as anastrozole, letrozole, exemestane and selective estrogen down-regulator (SERD) fulvestrant are used mostly to treat breast cancer estrogen receptor positive in post-menopausal women. These drugs are given either through the oral route or by intramuscular injection. They have shown great inter-individual variability with a risk of cardiometabolic disorders. Hence the importance of their therapeutic drug monitoring not only for exposure-efficacy but also exposure-toxicity. We describe here a LC-MS/MS method for the simultaneous quantification of anastrozole, letrozole, exemestane and fulvestrant in human plasma.
METHODS: Plasma samples were prepared by a single-step protein precipitation. The liquid chromatography system was paired with a triple quadrupole mass spectrometer. Quantification were achieved in Multiple Reactions Monitoring mode and the electrospray ionization was in positive mode.
RESULTS: The method demonstrated consistent analytical performance across various parameters, including linearity, specificity, sensitivity, matrix effect, upper and lower limits of quantification, extraction recovery, precision, accuracy, hemolysis effect, dilution integrity, and stability under different storage conditions, in accordance with established guidelines. The analysis time for each run was 4 min. Calibration curves exhibited linearity within the 1-100 ng/mL range, with correlation coefficients > 0.99 for the four analytes. Plasma concentrations from 42 patients were integrated into the selected calibration. Stability assessments indicated that the four drugs remained stable at - 20 °C for three months, 15 days under refrigeration, up to 7 days at room temperature, and after three freeze-thaw cycles.
CONCLUSIONS: We have developed and validated this quantitative method for therapeutic drug monitoring of those four hormone therapy drugs:anastrozole, letrozole, fulvestrant and exemestane. This method can be also used for future clinical pharmacokinetics /pharmacodynamics studies.
METHODS: Plasma samples were prepared by a single-step protein precipitation. The liquid chromatography system was paired with a triple quadrupole mass spectrometer. Quantification were achieved in Multiple Reactions Monitoring mode and the electrospray ionization was in positive mode.
RESULTS: The method demonstrated consistent analytical performance across various parameters, including linearity, specificity, sensitivity, matrix effect, upper and lower limits of quantification, extraction recovery, precision, accuracy, hemolysis effect, dilution integrity, and stability under different storage conditions, in accordance with established guidelines. The analysis time for each run was 4 min. Calibration curves exhibited linearity within the 1-100 ng/mL range, with correlation coefficients > 0.99 for the four analytes. Plasma concentrations from 42 patients were integrated into the selected calibration. Stability assessments indicated that the four drugs remained stable at - 20 °C for three months, 15 days under refrigeration, up to 7 days at room temperature, and after three freeze-thaw cycles.
CONCLUSIONS: We have developed and validated this quantitative method for therapeutic drug monitoring of those four hormone therapy drugs:anastrozole, letrozole, fulvestrant and exemestane. This method can be also used for future clinical pharmacokinetics /pharmacodynamics studies.
摘要：
背景：芳香酶抑制剂如阿那曲唑，来曲唑,依西美坦和选择性雌激素下调(SERD)氟维司群主要用于治疗绝经后女性雌激素受体阳性的乳腺癌.这些药物通过口服途径或肌内注射给予。他们已经显示出巨大的个体间变异性，有心脏代谢紊乱的风险。因此，它们的治疗药物监测不仅对暴露功效而且对暴露毒性都很重要。我们在这里描述了同时定量阿那曲唑的LC-MS/MS方法，来曲唑,人血浆中的依西美坦和氟维司群。
方法:通过一步蛋白沉淀制备血浆样品。液相色谱系统与三重四极杆质谱仪配对。在多反应监测模式下实现定量,并且电喷雾电离处于正模式。
结果：该方法在各种参数中表现出一致的分析性能，包括线性，特异性，灵敏度,基体效应，定量的上限和下限，提取回收，精度,准确度,溶血作用,稀释完整性，以及在不同储存条件下的稳定性，按照既定的指导方针。每次运行的分析时间为4分钟。校准曲线在1-100ng/mL范围内呈线性，四种分析物的相关系数>0.99。将来自42名患者的血浆浓度整合到所选择的校准中。稳定性评估表明，四种药物在-20°C下保持稳定三个月，冷藏15天，在室温下长达7天，经过三个冻融循环。
结论：我们已经开发并验证了这种定量方法，用于监测这四种激素治疗药物：阿那曲唑，来曲唑,氟维司群和依西美坦。该方法也可用于未来的临床药代动力学/药效学研究。
方法:通过一步蛋白沉淀制备血浆样品。液相色谱系统与三重四极杆质谱仪配对。在多反应监测模式下实现定量,并且电喷雾电离处于正模式。
结果：该方法在各种参数中表现出一致的分析性能，包括线性，特异性，灵敏度,基体效应，定量的上限和下限，提取回收，精度,准确度,溶血作用,稀释完整性，以及在不同储存条件下的稳定性，按照既定的指导方针。每次运行的分析时间为4分钟。校准曲线在1-100ng/mL范围内呈线性，四种分析物的相关系数>0.99。将来自42名患者的血浆浓度整合到所选择的校准中。稳定性评估表明，四种药物在-20°C下保持稳定三个月，冷藏15天，在室温下长达7天，经过三个冻融循环。
结论：我们已经开发并验证了这种定量方法，用于监测这四种激素治疗药物：阿那曲唑，来曲唑,氟维司群和依西美坦。该方法也可用于未来的临床药代动力学/药效学研究。
