Quantification of cisplatin, carboplatin and oxaliplatin in spiked human plasma samples by ICP-SFMS and hydrophilic interaction liquid chromatography (HILIC) combined with ICP-MS detection
Quantification of cisplatin, carboplatin and oxaliplatin in spiked human plasma samples by ICP-SFMS and hydrophilic interaction liquid chromatography (HILIC) combined with ICP-MS detection
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DOI：
10.1039/b907011g
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发表时间：
2009-01-01
影响因子：
3.4
通讯作者：
Hann, Stephan
中科院分区：
文献类型：
--
作者：
Falta, Thomas;Koellensperger, Gunda;Hann, Stephan
治疗药物监测致力于确定患者血液中游离和完整的药物。通过测量血浆超滤液中的总铂水平来确定抑癌铂化合物 (CPC) 的游离分数。在这项工作中，作为起点，在离体实验中通过 ICP-SFMS 测量微波消解后的总铂，评估了顺铂、卡铂和奥沙利铂在不同血液区室（即全血、血浆、残留物（沉淀部分）、血浆超滤液和蛋白质残留部分）中的分布。结果清楚地表明，分布与初始浓度无关，但取决于所用药物。血浆超滤液中顺铂、卡铂和奥沙利铂的铂含量分别为16.8 +/- 1.3%、56.8 +/- 0.1%和10.4 +/- 1.0%。血浆样品的乙腈沉淀提供了相应的结果，简化并加速了样品制备（血浆超滤和总消化为 5 分钟与 150 分钟）。该方法可以与使用亲水相互作用液相色谱 (HILIC) 和 ICP-QMS 检测的新型形态分析方法完美结合。总铂水平与物种选择性结果的比较显示，88.0 +/- 12.0% 的顺铂和 106.4 +/- 7.7% 的卡铂以母体药物形式存在，而只有 34.3 +/- 0.4% 的奥沙利铂以完整状态存在。
Therapeutic drug monitoring addresses the determination of the free and intact drug in patient blood. The free fraction of cancerostatic platinum compounds (CPC) is determined by measurement of total platinum levels in plasma ultrafiltrate. In this work, as a starting point, the distribution of cisplatin, carboplatin and oxaliplatin among different blood compartments, i.e. whole blood, plasma, residue (pellet fraction), plasma-ultrafiltrate and protein-residue fraction, was assessed in an ex vivo experiment via ICP-SFMS measurement of total platinum after microwave digestion. The results clearly showed that the distribution is independent of the initial concentration but dependent on the used drug. The platinum in the plasma-ultrafiltrate amounted to 16.8 +/- 1.3%, 56.8 +/- 0.1% and 10.4 +/- 1.0% for cisplatin, carboplatin and oxaliplatin, respectively. Acetonitrile precipitation of plasma samples delivered corresponding results simplifying and accelerating (5 min vs. 150 min for plasma ultrafiltration and total digestion) sample preparation. This method could be ideally combined with a novel speciation analytical approach using hydrophilic interaction liquid chromatography (HILIC) with ICP-QMS detection. A comparison of the total platinum levels to species selective results revealed that 88.0 +/- 12.0% of cisplatin and 106.4 +/- 7.7% of carboplatin were present as parent drug, whereas only 34.3 +/- 0.4% of oxaliplatin were present in the intact state.