Kehl Niklas, Schlichtig Katja, Dürr Pauline, Bellut Laura, Dörje Frank, Fietkau Rainer, Pavel Marianne, Mackensen Andreas, Wullich Bernd, Maas Renke, Fromm Martin F, Gessner Arne, Taudte R Verena
Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), University Hospital Erlangen, 91054 Erlangen, Germany.
Cancers (Basel). 2021 Dec 16;13(24):6329. doi: 10.3390/cancers13246329.
Oral anticancer drugs have led to significant improvements in the treatment of multiple tumor entities. However, in patients undergoing oral antitumor therapy, plasma concentrations are highly variable, resulting in risks of reduced therapeutic effects or an increase in side effects. One important tool to reduce this variability is therapeutic drug monitoring. In this work we describe a method to simultaneously quantify the plasma concentrations of 57 oral antitumor agents. Quantification of these drugs was achieved using liquid chromatography coupled to an Orbitrap mass spectrometer. The method was fully validated according to the FDA guidelines and constitutes a simple and robust way for exposure monitoring of a wide variety of oral anticancer drugs. Applicability to clinical routine was demonstrated by the analysis of 71 plasma samples taken from 39 patients. In summary, this new multi-drug method allows simultaneous quantification of 57 oral antitumor drugs, which can be applied to exposure monitoring in clinical studies, taking into account the broad variety of oral antitumor drugs prescribed in clinical routine.
口服抗癌药物已使多种肿瘤实体的治疗取得了显著进展。然而，在接受口服抗肿瘤治疗的患者中，血浆浓度高度可变，导致治疗效果降低或副作用增加的风险。减少这种变异性的一个重要工具是治疗药物监测。在这项工作中，我们描述了一种同时定量57种口服抗肿瘤药物血浆浓度的方法。使用液相色谱与Orbitrap质谱仪联用实现了这些药物的定量。该方法根据FDA指南进行了全面验证，是一种简单且稳健的多种口服抗癌药物暴露监测方法。通过分析来自39名患者的71份血浆样本，证明了其在临床常规中的适用性。总之，这种新的多药物方法能够同时定量57种口服抗肿瘤药物，鉴于临床常规中开具的口服抗肿瘤药物种类繁多，该方法可应用于临床研究中的暴露监测。
