用于定量分析人皮肤肿瘤中培坎替尼的源内碰撞诱导解离液相色谱-串联质谱法的开发与验证
Development and validation of LC-MS/MS with in-source collision-induced dissociation for the quantification of pegcantratinib in human skin tumors.
作者信息
Zangarini Monique, Rajan Neil, Danilenko Marina, Berry Philip, Traversa Silvio, Veal Gareth J
机构信息
Newcastle Cancer Centre Pharmacology Group, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
出版信息
Bioanalysis. 2017 Feb;9(3):279-288. doi: 10.4155/bio-2016-0199. Epub 2017 Jan 23.
AIM
Pegcantratinib is a mini-PEGylated K252a derivative, under clinical evaluation as an anticancer agent acting through inhibition of the tropomyosin receptor kinase. A method for quantifying pegcantratinib in skin tumor biopsies of patients was required to determine tumor drug penetration.
METHODS & RESULTS: A sensitive and PEGylated molecule specific HPLC-MS/MS method coupled with in-source collision-induced dissociation was developed. The method exhibited excellent precision (coefficient of variation ≤8.5%), accuracy in the range 95-102%, high and consistent recovery and no matrix effect. The assay was linear across a range of 1-500 ng/ml, with a limit of quantitation of 2.5 ng/ml.
CONCLUSION
We have developed and validated a method for analyzing pegcantratinib in human tumor biopsies, with the approach successfully applied to clinical trial samples.
目的
培康替尼是一种微型聚乙二醇化的K252a衍生物，正在作为一种通过抑制原肌球蛋白受体激酶发挥作用的抗癌药物进行临床评估。需要一种方法来定量患者皮肤肿瘤活检组织中的培康替尼，以确定肿瘤药物渗透情况。
方法与结果
开发了一种灵敏且对聚乙二醇化分子具有特异性的HPLC-MS/MS方法，并结合源内碰撞诱导解离。该方法具有出色的精密度（变异系数≤8.5%）、95-102%范围内的准确度、高且一致的回收率以及无基质效应。该测定法在1-500 ng/ml范围内呈线性，定量限为2.5 ng/ml。
结论
我们已开发并验证了一种用于分析人肿瘤活检组织中培康替尼的方法，该方法已成功应用于临床试验样本。
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