Turković Lu, Bočkor Luka, Ekpenyong Oscar, Silovski Tajana, Lovrić Mila, Crnković Slaven, Nigović Biljana, Sertić Miranda
Department of Pharmaceutical Analysis, Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovacica 1, 10000 Zagreb, Croatia.
Centre for Applied Bioanthropology, Institute for Anthropological Research, Ljudevita Gaja 32, 10000 Zagreb, Croatia.
Pharmaceuticals (Basel). 2022 May 16;15(5):614. doi: 10.3390/ph15050614.
Palbociclib, ribociclib and abemaciclib were recently approved as chemotherapeutic agents and are currently in the post-marketing surveillance phase. They are used in combination with aromatase inhibitors anastrozole and letrozole or antiestrogen fulvestrant for HR+, HER2- breast cancer treatment. Here, a novel bioanalytical LC-ESI-MS/MS method was developed for the quantitation of these six drugs in human plasma. The samples were prepared by simple protein precipitation followed by solvent evaporation. A Kinetex biphenyl column (150 × 4.6 mm, 2.6 µm) used for chromatographic analysis adequately resolved even the closely eluting aromatase inhibitors' peaks. The mobile phase consisted of 0.1% formic acid in water and in ACN, in a linear gradient. An additional gradient step was added to eliminate the observed carry-over. The proposed method was fully validated in the relevant linear ranges covering the expected plasma concentrations of all six drugs (correlation coefficients between 0.9996 and 0.9931). The intra-day method precision (CV) ranged from 3.1% to 15%, while intra-day accuracy (%bias) was between -1.5% and 15.0%. The inter-day precision ranged from 1.6% to 14.9%, with accuracy between -14.3% and 14.6%, which is in accordance with the EMA and ICH guidelines on bioanalytical method validation. The method was successfully applied to samples from patients treated for HR+, HER2- breast cancer.
帕博西尼、瑞博西尼和阿贝西利最近被批准作为化疗药物，目前正处于上市后监测阶段。它们与芳香酶抑制剂阿那曲唑和来曲唑或抗雌激素氟维司群联合用于HR +、HER2 - 乳腺癌的治疗。在此，开发了一种新型生物分析液相色谱 - 电喷雾串联质谱（LC - ESI - MS/MS）方法，用于定量人血浆中的这六种药物。样品通过简单的蛋白质沉淀，然后蒸发溶剂来制备。用于色谱分析的Kinetex联苯柱（150×4.6 mm，2.6 µm）甚至能充分分离出洗脱峰相近的芳香酶抑制剂。流动相由含0.1%甲酸的水和乙腈组成，呈线性梯度。增加了一个额外的梯度步骤以消除观察到的残留。所提出的方法在涵盖所有六种药物预期血浆浓度的相关线性范围内得到了充分验证（相关系数在0.9996至0.9931之间）。日内方法精密度（CV）范围为3.1%至15%，而日内准确度（%偏差）在 - 1.5%至15.0%之间。日间精密度范围为1.6%至14.9%，准确度在 - 14.3%至14.6%之间，这符合欧洲药品管理局（EMA）和人用药品注册技术要求国际协调会（ICH）关于生物分析方法验证的指南。该方法已成功应用于HR +、HER2 - 乳腺癌治疗患者的样本。
