Evaluation of a capillary microsampling device for analyzing plasma lenvatinib concentration in patients with hepatocellular carcinoma
Evaluation of a capillary microsampling device for analyzing plasma lenvatinib concentration in patients with hepatocellular carcinoma
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毛细血管微量取样装置分析肝细胞癌患者血浆乐伐替尼浓度的评价
DOI：
10.1097/ftd.0000000000001013
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发表时间：
2022
影响因子：
2.5
通讯作者：
Nariyasu Mano
中科院分区：
文献类型：
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作者：
Akihiro Saito;Masafumi Kikuchi;Yuko Matsumoto;Erina Sugawara;Gesshu Takao;Hayato Inomata; Akane Takahashi;Yuji Sato;Masaki Kumondai;Yu Sato;Toshihiro Sato;Masashi Ninomiya;Jun Inoue;Masamitsu Maekawa;Nariyasu Mano
背景：抗癌药物Lenvima(Lenvatinib)有严重的副作用。治疗性药物监测有助于确保其有效性和安全性。定期和最佳的采血时间是困难的，特别是当lenvatinib自我用药的时候。使用易于操作的微采样翼(MSW)进行微采样可能有助于绕过这一问题。然而，目前的莱瓦替尼检测方法不够灵敏，无法检测到其在微量样品中的浓度(<；50-250μL)。因此，本研究的目的有两个方面：(1)建立一种分析方法来估计微量样品中的雷瓦替尼血药浓度；(2)验证该方法是否适用于通过城市生活垃圾采集的不能切除的肝细胞癌患者的微量(5.6μL)血浆样品。使用这一新的方法，测量了常规采血和城市生活垃圾采血的雷瓦替尼血药浓度谷值。采集11例肝细胞癌患者的静脉全血35份。结果：城市生活垃圾与常规静脉血样的平均血药浓度估计值无显著差异。日间和日间测定的变异系数较低。到第5天，城市生活垃圾样品中的lenvatinib浓度是初始日浓度(储存在25℃或4℃)的85%-115%。结论：本研究建立的质谱学方法准确测定人血浆中的莱瓦替尼浓度，重现性好。因此，当MSW与这一新的液相色谱-电喷雾电离串联质谱仪检测方法结合使用时，可以作为一种有用的微量采样设备用于肝癌患者的Lenvatinib治疗药物监测。
Background:The anticancer drug, Lenvima (lenvatinib), has severe side effects. Therapeutic drug monitoring helps ensure its efficacy and safety. Regular and optimally timed blood sampling is tough, especially when lenvatinib is self-medicated. Microsampling using the easy to handle Microsampling Wing (MSW) may help circumvent this problem. However, current lenvatinib detection methods are not sensitive enough to detect its concentrations in microsamples (< 50–250 μL). Thus, the aim of this study was 2-fold (1) develop an analytic method to estimate plasma lenvatinib concentrations in microsamples and (2) verify whether this method works on micro (5.6 μL) blood plasma samples obtained clinically through MSW from patients with unresectable hepatocellular carcinoma (HCC).Methods:A simple, highly sensitive, and specific liquid chromatography–electrospray ionization tandem mass spectrometry method was developed. Using this novel protocol, the trough blood plasma concentration of lenvatinib was measured for both blood sampled conventionally and that using MSW. Thirty-five venous whole blood samples were obtained from 11 patients with HCC. Furthermore, the stability of lenvatinib in MSW samples during storage was evaluated.Results:The mean plasma lenvatinib concentration estimates were not significantly different between the MSW and conventional venous blood samples. CV for interday and intraday assays was low. Up to day 5, the lenvatinib concentration in the MSW samples was 85%–115% of the initial day concentration (when stored at 25 C or 4 C). The interference of endogenous matrix components in the human plasma was low.Conclusions:These results indicate that the novel mass spectrometry protocol accurately measures lenvatinib in human plasma and is reproducible. Thus, MSW could be a useful microsampling device for lenvatinib therapeutic drug monitoring in patients with HCC when used in combination with this novel liquid chromatography–electrospray ionization tandem mass spectrometry detection method.