Habler Katharina, Vogeser Michael, Teupser Daniel
Institute of Laboratory Medicine, University Hospital, LMU Munich, Germany.
J Mass Spectrom Adv Clin Lab. 2022 Feb 7;24:15-21. doi: 10.1016/j.jmsacl.2022.02.001. eCollection 2022 Apr.
Abemaciclib is a new oral targeted treatment option for patients with advanced breast cancer. The emerging field of oral antitumor therapeutics presents challenges for both patients and healthcare teams; non-adherence and high inter-individual pharmacokinetic variability can influence response rates.
For monitoring abemaciclib in human sera, a rapid novel ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed and fully validated. Sample preparation was based on a protein precipitation step followed by on-line solid phase extraction. Chromatographic separation was achieved using a biphenyl column and the isotope labeled standard abemaciclib-d was used for quantification.
The method showed linearity over a wide calibration range from 20.0 to 2500 ng/mL. With accuracies and precisions of ≤13.9% and ≤4.42%, respectively, the validation results were within the criteria of acceptance. The fitness of the method was tested by monitoring abemaciclib levels under compassionate use for a single individual.
The novelty of the presented two dimensional isotope dilution UHPLC-MS/MS method is in the semi-automated sample preparation, which results in negligible matrix effects, thereby allowing the introduction of abemaciclib into robust routine therapeutic drug monitoring (TDM). This method provides an efficient tool to verify the usefulness of personalized anticancer therapy in clinical practice.
阿贝西利是晚期乳腺癌患者的一种新型口服靶向治疗选择。口服抗肿瘤治疗这一新兴领域给患者和医疗团队都带来了挑战；用药依从性差和个体间药代动力学高度变异会影响缓解率。
为监测人血清中的阿贝西利，开发并全面验证了一种快速的新型超高效液相色谱 - 串联质谱法。样品制备基于蛋白质沉淀步骤，随后进行在线固相萃取。使用联苯柱实现色谱分离，并使用同位素标记的标准品阿贝西利 - d进行定量。
该方法在20.0至2500 ng/mL的宽校准范围内呈线性。准确度和精密度分别≤13.9%和≤4.42%，验证结果在可接受标准范围内。通过监测一名患者在同情用药情况下的阿贝西利水平对该方法的适用性进行了测试。
所提出的二维同位素稀释UHPLC - MS/MS方法的新颖之处在于半自动样品制备，这导致基质效应可忽略不计，从而使阿贝西利能够用于可靠的常规治疗药物监测（TDM）。该方法为在临床实践中验证个性化抗癌治疗的有效性提供了一种有效工具。
