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.
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。