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. 2018 Nov 6;23(11):2894.
doi: 10.3390/molecules23112894.

An Accurate and Effective Method for Measuring Osimertinib by UPLC-TOF-MS and Its Pharmacokinetic Study in Rats

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Free PMC article

An Accurate and Effective Method for Measuring Osimertinib by UPLC-TOF-MS and Its Pharmacokinetic Study in Rats

Song-Tao Dong et al. Molecules. .
Free PMC article

Abstract

Osimertinib, a new-generation inhibitor of the epidermal growth factor, has been used for the clinical treatment of advanced T790M mutation-positive tumors. In this research, an original analysis method was established for the quantification of osimertinib by ultra-performance liquid chromatography with time of flight mass spectrometry (UPLC-TOF-MS) in rat plasma. After protein precipitation with acetonitrile and sorafinib (internal standard, IS), they were chromatographed through a Waters XTerra MS C18 column. The mobile phase was acetonitrile and water (including 0.1% ammonia). The relative standard deviation (RSD) of the intra- and inter-day results ranged from 5.38 to 9.76% and from 6.02 to 9.46%, respectively, and the extraction recovery and matrix effects were calculated to range from 84.31 to 96.14% and from 91.46 to 97.18%, respectively. The results illustrated that the analysis method had sufficient specificity, accuracy and precision. Meanwhile, the UPLC-TOF-MS method for osimertinib was successfully applied into the pharmacokinetics of SD rats.

Keywords: UPLC-TOF-MS; osimertinib; pharmacokinetics; rat.

Conflict of interest statement

The authors declared no conflict of interest.

Figures

Figure 1
Figure 1
Structures of osimertinib (molecular weight = 499.619 Da) and sorafenib (molecular weight = 464.825 Da).
Figure 2
Figure 2
Product ion scan of osimertinib 500.2768 → 72.0810 (A), and IS 465.0953 → 270.0882 (B).
Figure 3
Figure 3
Typical chromatograms of (A) standard osimertinib (20 ng/mL) in rat plasma, (B) pharmacokinetic plasma sample, (C) blank plasma, (D) standard ion of sorafenib (IS) (500 ng/mL) in rat plasma, (E) pharmacokinetic plasma sample, and (F) blank plasma.
Figure 3
Figure 3
Typical chromatograms of (A) standard osimertinib (20 ng/mL) in rat plasma, (B) pharmacokinetic plasma sample, (C) blank plasma, (D) standard ion of sorafenib (IS) (500 ng/mL) in rat plasma, (E) pharmacokinetic plasma sample, and (F) blank plasma.
Figure 4
Figure 4
Plasma concentration-time profile after single oral administration of osimertinib (4.5 mg/kg) to rats. Data are expressed as the mean ± SD (n = 7).

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References

    1. Chen Z., Chen Y., Xu M., Chen L., Zhang X., To K.K., Zhao H., Wang F., Xia Z., Chen X., et al. Osimertinib (AZD9291) enhanced the efficacy of chemotherapeutic agents in ABCB1- and ABCG2-overexpressing cells in vitro, in vivo, and ex vivo. Mol. Cancer Ther. 2016;15:1845–1858. doi: 10.1158/1535-7163.MCT-15-0939. - DOI - PubMed
    1. Cross D.A., Ashton S.E., Ghiorghiu S., Eberlein C., Nebhan C.A., Spitzler P.J., Orme J.P., Finlay M.R., Ward R.A., Mellor M.J., et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014;4:1046–1061. doi: 10.1158/2159-8290.CD-14-0337. - DOI - PMC - PubMed
    1. Yang M., Tong X., Xu X., Zheng E., Ni J., Li J., Yan J., Shao Y.W., Zhao G. Case Report: Osimertinib achieved remarkable and sustained disease control in an advanced non-small-cell lung cancer harboring EGFR H773L/V774M mutation complex. Lung Cancer. 2018;121:1–4. doi: 10.1016/j.lungcan.2018.04.006. - DOI - PubMed
    1. Gao X., Le X., Costa D.B. The safety and efficacy of osimertinib for the treatment of EGFR T790M mutation positive non-small-cell lung cancer. Expert Rev. Anticancer Ther. 2016;16:383–390. doi: 10.1586/14737140.2016.1162103. - DOI - PMC - PubMed
    1. Ricciuti B., Chiari R., Chiarini P., Crino L., Maiettini D., Ludovini V., Metro G. Osimertinib (AZD9291) and CNS response in two radiotherapy-naive patients with EGFR-Mutant and T790M-Positive advanced non-small cell lung cancer. Clin. Drug Investing. 2016;36:683–686. doi: 10.1007/s40261-016-0411-1. - DOI - PubMed
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