Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium; Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Talanta. 2017 Nov 1;174:171-178. doi: 10.1016/j.talanta.2017.06.002. Epub 2017 Jun 3.
Cisplatin is a first-line chemotherapeutic for the treatment of a wide variety of cancers since its discovery in the 1960s. Although various techniques have been reported for the measurement of total platinum in biological matrices, such as inductively coupled plasma-mass spectrometry and derivatization procedures, a specific, sensitive and robust assay for the quantification of intact cisplatin is still lacking. Therefore, we present a rapid, selective, sensitive, and reliable UHPLC-MS/MS based method for the determination of intact cisplatin in human plasma in support of a Phase II clinical trial. The optimal chromatographic behavior of cisplatin was achieved on a Syncronis HILIC column (50 × 2.1mm, 1.7µm, zwitterionic stationary phase). The retention behavior of cisplatin on this zwitterion-based stationary phase was well described by an adsorptive interaction model. A simple sample preparation based on protein precipitation combined with the removal of phospholipids by HybridSPE-precipitation was developed. The method was proven to be free of a relative matrix effect. The assay was validated within a range of 20 - 10,000ng/mL using 100μL of plasma sample. The intra and inter-day precisions were all less than 7.6%, and none of the bias was greater than 13.1%, thus corroborating that the developed method is precise and accurate. As a proof of concept, the assay has been successfully applied to plasma samples obtained from different patients who were enrolled in the Phase II trial and were treated with cisplatin.
顺铂自 20 世纪 60 年代发现以来，一直是治疗多种癌症的一线化疗药物。尽管已经报道了多种技术来测量生物基质中的总铂，如电感耦合等离子体质谱法和衍生化程序，但仍然缺乏用于定量完整顺铂的特异性、灵敏性和稳健的测定方法。因此，我们提出了一种快速、选择性、灵敏和可靠的 UHPLC-MS/MS 方法，用于支持 II 期临床试验的人血浆中完整顺铂的定量。顺铂的最佳色谱行为在 Syncronis HILIC 柱（50×2.1mm，1.7µm，两性离子固定相）上实现。顺铂在这种基于两性离子的固定相上的保留行为很好地用吸附相互作用模型来描述。开发了一种简单的基于蛋白质沉淀的样品制备方法，并结合 HybridSPE-沉淀去除磷脂。该方法证明无相对基质效应。该方法在 20-10000ng/mL 范围内使用 100μL 血浆样品进行验证。日内和日间精密度均小于 7.6%，且无偏差大于 13.1%，这证明了所开发的方法具有精确性和准确性。作为概念验证，该测定方法已成功应用于接受顺铂治疗的不同患者的 II 期试验获得的血浆样品。
