Validation of an LC-MS/MS method for the determination of epirubicin in human serum of patients undergoing Drug Eluting Microsphere-Transarterial Chemoembolization (DEM-TACE)
Validation of an LC-MS/MS method for the determination of epirubicin in human serum of patients undergoing Drug Eluting Microsphere-Transarterial Chemoembolization (DEM-TACE)
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DOI：
10.1016/j.jchromb.2009.08.054
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发表时间：
2009-11-01
影响因子：
3
通讯作者：
Minoia, Claudio
中科院分区：
文献类型：
--
作者：
Sottani, Cristina;Leoni, Emanuela;Minoia, Claudio
药物洗脱微球-肝动脉化疗栓塞术(DEM-TACE)是一种可控给药的新型给药系统，可用于结直肠癌肝转移的化疗栓塞术。DEM-TACE的重点是以比传统癌症化疗更低的全身浓度获得更高浓度的药物到肿瘤。因此，设计了一种特异、准确和灵敏的LC-ESI-MS/MS分析方法，以检测和定量微球肝动脉化疗栓塞术中预期的表阿霉素浓度。血清样品保持酸性(pH约为3.5)，样品制备过程包括用HLBOASIS(R)色谱柱使用二氯甲烷/异丙醇/甲醇混合溶液进行固相萃取(SPE)程序，以回收表阿霉素。采用反相高效液相色谱(RP-HPLC)与串联质谱仪(MS/MS)联用。通过对4个质控样品(QCS)、5个不同粘土样品的分析，考察了该方法的准确度、精密度和基质效应。验证参数通过加标血清样本的回收研究进行评估。在质量控制水平(5、40、80和150微克/L)下，回收率在92-98%之间，相对标准偏差始终小于3.7%。该方法的检出限为1微克/升，并用于考察两种市售微球在人体循环系统中释放表阿霉素的不同能力。(C)2009爱思唯尔B.V.保留所有权利。
Drug Eluting Microsphere-Transarterial Chemoembolization (DEM-TACE) is a new delivery system to administrate drugs in a controlled manner useful for application in the chemoembolization of colorectal cancer metastases to the liver. DEM-TACE is focused to obtain higher concentrations of the drug to the tumor with lower systemic concentrations than traditional cancer chemotherapy. Therefore a specific, precise and sensitive LC-ESI-MS/MS assay procedure was properly designed to detect and quantify epirubicin at the concentrations expected from a transarterial chemoembolization with microspheres. Serum samples were kept acidic (pH approximately of 3.5) and sample preparation consisted of a solid phase extraction (SPE) Procedure with HLB OASIS (R) cartridges using a methylene chloride/2-propanol/methanol mixture solution to recover epirubicin. The analyses consisted of reversed-phase high-performance liquid chromatography (rp-HPLC) coupled with tandem mass spectrometry (MS/MS). Accuracy, precision and matrix effect of this procedure were carried Out by analyzing four quality control samples (QCs) oil five separate clays. The validation parameters were assessed by recovery Studies of spiked serum samples. Recoveries were found to vary between 92 and 98% at the QC levels (5, 40, 80 and 150 mu g/L) with relative standard deviation (RSD) always less than 3.7%. The limit of detection (LOD) was set at 1 mu g/L. The developed procedure has been also applied to investigate the different capability of two types of commercially available microspheres to release epirubicin into the human circulatory system. (C) 2009 Elsevier B.V. All rights reserved.