Development of an LC–MS/MS-based method for quantitation of osimertinib in human plasma and cerebrospinal fluid

• Published in: Bioanalysis Vol. 11; no. 9; pp. 847 - 854
• Main Authors: Irie, Kei, Nanjo, Shigeki, Hata, Akito, Yamasaki, Yuta, Okada, Yutaka, Katakami, Nobuyuki, Fukushima, Shoji
• Format: Journal Article
• Language: English
• Published: England Future Science Ltd 01.05.2019; Newlands Press
• Subjects: Accuracy; Acrylamides - blood; Acrylamides - cerebrospinal fluid; Acrylamides - chemistry; Adsorption; Aniline Compounds - blood; Aniline Compounds - cerebrospinal fluid; Aniline Compounds - chemistry; AZD9291; Biomedical research; Blood Chemical Analysis - methods; Calibration; Cerebrospinal fluid; Chromatography, Liquid; EGFR-TKI; Humans; LC–MS/MS; Limit of Detection; Metastasis; Mutation; nonspecific binding; Plasma; Proteins; Quality control; Quantitation; Tandem Mass Spectrometry; Targeted cancer therapy; United States > US; Japan; EGFR-TKI; LC–MS/MS; AZD9291; nonspecific binding; cerebrospinal fluid
• ISSN: 1757-6180; 1757-6199
• DOI: 10.4155/bio-2018-0292

The transitivity of osimertinib to cerebrospinal fluid (CSF) is of clinical concern. A quantitative LC–MS/MS method for the determination of osimertinib in human plasma and CSF was developed to evaluate its transitivity. The calibration range was 40–1000 nM in plasma and 0.8–100 nM in CSF. Accuracy and precision were within 15%. Osimertinib in the CSF but not in plasma strongly adsorbed onto the storage container. The mean adsorbed loss of osimertinib was 45.5% in CSF. Nonspecific binding in CSF was decreased by protein addition (mean loss = 5.8%). A robust validated method was developed for the quantification of osimertinib in human plasma and CSF.