基于质谱的超快速定量方法用于分析临床试验中人类血浆样本中的色瑞替尼。

Ultrafast quantitative MS-based method for ceritinib analysis in human plasma samples from clinical trial.

作者信息

Lanshoeft Christian, Heudi Olivier, Raccuglia Marc, Leuthold Luc Alexis, Picard Franck, Kretz Olivier

机构信息

Novartis Pharma AG, DMPK/Bioanalytics, Forum 1 Novartis Campus, 4056 Basel, Switzerland.

出版信息

Bioanalysis. 2015;7(4):425-35. doi: 10.4155/bio.14.292.

DOI:10.4155/bio.14.292

PMID:25747762

Abstract

AIM

An ultrafast, sensitive, selective and robust LDTD-APCI-MS/MS method was developed for the quantification of ceritinib in human plasma.

RESULTS

Samples were protein precipitated using acetonitrile containing [(13)C6]-ceritinib as internal standard. The assay was validated over a concentration range from 5.00 to 1000 ng/ml. Intra- and inter-day precision and accuracy met acceptance from EMA and US FDA guidelines. The normalized recovery was 69%, whereas no carryover and matrix effects were observed. The method was applied to clinical samples and resultant data were consistent with the LC-ESI-MS/MS reference method.

CONCLUSION

The new assay is suitable for ceritinib quantification in clinical trials, whereas the analysis time is significantly reduced to 10 s.

摘要

目的

开发一种超快速、灵敏、选择性强且稳健的液相色谱-大气压化学电离串联质谱法（LDTD-APCI-MS/MS）用于定量测定人血浆中的色瑞替尼。

结果

使用含[(13)C6]-色瑞替尼作为内标的乙腈沉淀血浆样品中的蛋白质。该测定法在5.00至1000 ng/ml的浓度范围内得到验证。日内和日间精密度及准确度符合欧洲药品管理局（EMA）和美国食品药品监督管理局（US FDA）指南的验收标准。归一化回收率为69%，未观察到残留和基质效应。该方法应用于临床样品，所得数据与液相色谱-电喷雾电离串联质谱法（LC-ESI-MS/MS）参考方法一致。