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用于蒽环类药物分离的毛细管电泳激光诱导荧光检测法:应用于使用超滤的血浆中蛋白质结合分析。

CE-LIF method for the separation of anthracyclines: application to protein binding analysis in plasma using ultrafiltration.

作者信息

Whitaker Gillian, Lillquist Amy, Pasas Stephanie A, O'Connor Robert, Regan Fiona, Lunte Craig E, Smyth Malcolm R

机构信息

R. N. Adams Institute of Bioanalytical Chemistry, University of Kansas, KS, USA.

出版信息

J Sep Sci. 2008 Jun;31(10):1828-33. doi: 10.1002/jssc.200700629.

Abstract

Anthracyclines are chemotherapeutic drugs that are widely used in the treatment of cancers such as lung and ovarian cancers. The simultaneous determination of the anthracyclines, daunorubicin, doxorubicin and epirubicin, was achieved using CE coupled to LIF, with an excitation and emission wavelength of 488 and 560 nm, respectively. Using a borate buffer (105 mM, pH 9.0) and 30% MeOH, a stable and reproducible separation of the three anthracyclines was obtained. The method developed was shown to be capable of monitoring the therapeutic concentrations (50-50 000 ng/mL) of anthracyclines. LODs of 10 ng/mL, calculated at an S/N = 3, were achieved. Using the CE method developed, the in vitro protein binding to plasma was measured by ultrafiltration, and from this investigation the estimated protein binding was determined to be in the range of 77-94%.

摘要

蒽环类药物是广泛用于治疗肺癌和卵巢癌等癌症的化疗药物。采用毛细管电泳-激光诱导荧光检测法(CE-LIF),激发波长和发射波长分别为488 nm和560 nm,实现了对柔红霉素、阿霉素和表柔比星这三种蒽环类药物的同时测定。使用硼酸盐缓冲液(105 mM,pH 9.0)和30%甲醇,三种蒽环类药物实现了稳定且可重复的分离。所开发的方法能够监测蒽环类药物的治疗浓度(50 - 50000 ng/mL)。在信噪比(S/N)= 3时计算得出的检测限为10 ng/mL。使用所开发的毛细管电泳方法,通过超滤测定了体外蛋白质与血浆的结合情况,据此研究确定估计的蛋白质结合率在77% - 94%范围内。

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