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International Journal of Pharmacokinetics
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Preliminary Communication

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

    Kei Irie

    *Author for correspondence: Tel.: +81 78 302 4321; Fax: +81 78 302 5534;

    E-mail Address: kei_irie@kcho.jp

    Department of Pharmacy, Kobe City Hospital Organization, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-minami-machi, Chuo-ku, Kobe 650-0047, Japan

    Division of Pharmacy, Institute of Biomedical Research & Innovation Hospital, 2-2-1 Minatojima-minami-machi, Chuo-ku, Kobe 650-0047, Japan

    Division of Integrated Oncology, Institute of Biomedical Research & Innovation Hospital, 2-2-1 Minatojima-minami-machi, Chuo-ku, Kobe 650-0047, Japan

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    ,
    Shigeki Nanjo

    Division of Integrated Oncology, Institute of Biomedical Research & Innovation Hospital, 2-2-1 Minatojima-minami-machi, Chuo-ku, Kobe 650-0047, Japan

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    ,
    Akito Hata

    Division of Integrated Oncology, Institute of Biomedical Research & Innovation Hospital, 2-2-1 Minatojima-minami-machi, Chuo-ku, Kobe 650-0047, Japan

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    ,
    Yuta Yamasaki

    Department of Pharmaceutics, Faculty of Pharmaceutical Science, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan

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    ,
    Yutaka Okada

    Division of Integrated Oncology, Institute of Biomedical Research & Innovation Hospital, 2-2-1 Minatojima-minami-machi, Chuo-ku, Kobe 650-0047, Japan

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    ,
    Nobuyuki Katakami

    Division of Integrated Oncology, Institute of Biomedical Research & Innovation Hospital, 2-2-1 Minatojima-minami-machi, Chuo-ku, Kobe 650-0047, Japan

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    &
    Shoji Fukushima

    Department of Pharmaceutics, Faculty of Pharmaceutical Science, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan

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    Published Online:14 May 2019https://doi.org/10.4155/bio-2018-0292

    Abstract

    Aim: 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. Results: 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%). Conclusion: A robust validated method was developed for the quantification of osimertinib in human plasma and CSF.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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