Confirmation of drug delivery after liver chemoembolization: direct tissue doxorubicin measurement by UHPLC-MS-MS.

Confirmation of drug delivery after liver chemoembolization: direct tissue doxorubicin measurement by UHPLC-MS-MS.
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DOI:
10.1002/bmc.2727
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发表时间:
2012-12
影响因子:
1.8
通讯作者:
van Breemen, Richard B.
van Breemen, Richard B.
中科院分区:
医学4区
文献类型:
--
作者:
Baumgarten, Sigrid;Gaba, Ron C.;van Breemen, Richard B.

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由于肝癌很少适合手术,经导管动脉化疗栓塞术(TACE)被用于姑息治疗。在这个过程中,碘油中的阿霉素乳剂通过位于向肿瘤供应血流的动脉内的导管直接注射到肝肿瘤中。目前,对TACE期间多柔比星在治疗肿瘤内的递送和分散的影响因素的了解有限。本研究旨在开发和应用高压液相色谱-串联质谱(UHPLC-MS-MS)方法快速确认兔VX 2肝癌模型中TACE后的药物递送。使用UHPLC-MS-MS测量肝肿瘤中的阿霉素水平,并与计算机断层扫描测量的碘化油水平进行比较,碘化油是临床上用于指示药物递送的指标。我们发现,使用UHPLC-MS-MS测定的组织药物水平与TACE后肿瘤内的局部碘化油浓度(溶剂)无关,表明化疗药物如阿霉素在整个肿瘤中扩散,并且肿瘤部分缺乏碘化油染色并不一定表明TACE期间治疗不足。
Because liver cancer is rarely suitable for surgery, transcatheter arterial chemoembolization (TACE) is used for palliative therapy. In this procedure, an emulsion of doxorubicin in iodized oil is injected directly into liver tumors through a catheter positioned within the artery supplying blood flow to the tumor. At present, there is limited understanding of factors affecting the delivery and dispersion of doxorubicin within treated tumors during TACE. This study addresses the development and application of an ultrahigh pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS-MS) method for rapid confirmation of drug delivery after TACE in a rabbit VX2 liver cancer model. Doxorubicin levels in liver tumors were measured using UHPLC-MS-MS and compared with computed tomography measured levels of iodized oil, a metric used clinically to indicate drug delivery. We found that tissue drug levels determined using UHPLC-MS-MS did not correlate with the regional iodized oil concentration (vehicle) within tumors following TACE, suggesting that chemotherapeutic drugs like doxorubicin spread throughout tumors, and that lack of iodized oil staining in portions of a tumor does not necessarily indicate inadequate therapy during TACE.
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