人血浆中 Palbociclib、Ribociclib、Abemaciclib、M2、M20 和 Letrozole 的治疗监测:新型 LC-MS/MS 方法。

IF 2.8 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY
Therapeutic Drug Monitoring Pub Date : 2024-08-01 Epub Date: 2024-02-06 DOI:10.1097/FTD.0000000000001174
Bianca Posocco, Martina Zanchetta, Marco Orleni, Sara Gagno, Marcella Montico, Elena Peruzzi, Rossana Roncato, Lorenzo Gerratana, Serena Corsetti, Fabio Puglisi, Giuseppe Toffoli
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引用次数: 0

摘要

背景:使用细胞周期蛋白依赖性激酶抑制剂(CDK4/6is)进行治疗药物监测(TDM)是优化治疗效果的一种新方法。目前,palbociclib、ribociclib和abemaciclib是可用的CDK4/6is,主要与来曲唑联合用药。本研究旨在开发并验证一种LC-MS/MS方法,用于同时分析人血浆中的CDK4/6is、阿贝西利的2种活性代谢物(M2和M20)和来曲唑,供TDM研究使用:样品前处理包括用甲醇沉淀蛋白质,并用水性流动相稀释上清液。色谱分离采用反相 XBridge BEH C18 色谱柱(2.5 μm,3.0 × 75 mm XP),有机流动相为甲醇,水流动相为吡咯烷-吡咯烷甲酸铵(0.005:0.005 mol/L)缓冲液(pH 11.3)。使用三重四极杆质谱仪进行检测,ESI 源从负离子模式切换到正离子模式,并在多反应监测模式下进行采集:整个验证过程符合最新的监管准则。为受测化合物确定了以下分析范围(纳克/毫升):6-300,palbociclib 和来曲唑;120-6000,ribociclib;40-800,abemaciclib;20-400,M2 和 M20。所有结果均符合线性、准确度、精密度、选择性、灵敏度、基质效应和携带率的验收标准。共分析了 85 份患者样本,所有测量浓度均在有效范围内。重新分析样本的百分比差异从 -11.2% 到 7.0% 不等:一种简单、稳健的LC-MS/MS方法成功地验证了同时定量检测人血浆中CDK4/6is、M2、M20和来曲唑的有效性。该方法适用于测定患者样本中分析物的稳态谷浓度。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Therapeutic Monitoring of Palbociclib, Ribociclib, Abemaciclib, M2, M20, and Letrozole in Human Plasma: A Novel LC-MS/MS Method.

Background: Therapeutic drug monitoring (TDM) using cyclin-dependent kinase inhibitors (CDK4/6is) is a novel approach for optimizing treatment outcomes. Currently, palbociclib, ribociclib, and abemaciclib are the available CDK4/6is and are primarily coadministered with letrozole. This study aimed to develop and validate an LC-MS/MS method for the simultaneous analysis of CDK4/6is, 2 active metabolites of abemaciclib (M2 and M20), and letrozole in human plasma for use in TDM studies.

Methods: Sample pretreatment comprised protein precipitation with methanol and dilution of the supernatant with an aqueous mobile phase. Chromatographic separation was achieved using a reversed-phase XBridge BEH C18 column (2.5 μm, 3.0 × 75 mm XP), with methanol serving as the organic mobile phase and pyrrolidine-pyrrolidinium formate (0.005:0.005 mol/L) buffer (pH 11.3) as the aqueous mobile phase. A triple quadrupole mass spectrometer was used for the detection, with the ESI source switched from negative to positive ionization mode and the acquisition performed in multiple reaction monitoring mode.

Results: The complete validation procedure was successfully performed in accordance with the latest regulatory guidelines. The following analytical ranges (ng/mL) were established for the tested compounds: 6-300, palbociclib and letrozole; 120-6000, ribociclib; 40-800, abemaciclib; and 20-400, M2 and M20. All results met the acceptance criteria for linearity, accuracy, precision, selectivity, sensitivity, matrix effects, and carryover. A total of 85 patient samples were analyzed, and all measured concentrations were within the validated ranges. The percent difference for the reanalyzed samples ranged from -11.2% to 7.0%.

Conclusions: A simple and robust LC-MS/MS method was successfully validated for the simultaneous quantification of CDK4/6is, M2, M20, and letrozole in human plasma. The assay was found to be suitable for measuring steady-state trough concentrations of the analytes in patient samples.

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来源期刊
Therapeutic Drug Monitoring
Therapeutic Drug Monitoring 医学-毒理学
CiteScore
5.00
自引率
8.00%
发文量
213
审稿时长
4-8 weeks
期刊介绍: Therapeutic Drug Monitoring is a peer-reviewed, multidisciplinary journal directed to an audience of pharmacologists, clinical chemists, laboratorians, pharmacists, drug researchers and toxicologists. It fosters the exchange of knowledge among the various disciplines–clinical pharmacology, pathology, toxicology, analytical chemistry–that share a common interest in Therapeutic Drug Monitoring. The journal presents studies detailing the various factors that affect the rate and extent drugs are absorbed, metabolized, and excreted. Regular features include review articles on specific classes of drugs, original articles, case reports, technical notes, and continuing education articles.
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