A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor
A rapid, sensitive, and robust reversed-phase liquid chromatography with tandem mass spectrometry method was developed and validated for the determination of total and unbound ceritinib, a second-generation ALK inhibitor, in patient plasma and brain tumor tissue samples. Sample preparation involved...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-02-01
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| Series: | Journal of Pharmaceutical Analysis |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177917300953 |
| _version_ | 1818571821606240256 |
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| author | Xun Bao Jianmei Wu Nader Sanai Jing Li |
| author_facet | Xun Bao Jianmei Wu Nader Sanai Jing Li |
| author_sort | Xun Bao |
| collection | DOAJ |
| description | A rapid, sensitive, and robust reversed-phase liquid chromatography with tandem mass spectrometry method was developed and validated for the determination of total and unbound ceritinib, a second-generation ALK inhibitor, in patient plasma and brain tumor tissue samples. Sample preparation involved simple protein precipitation with acetonitrile. Chromatographic separation was achieved on a Waters ACQUITY UPLC BEH C18 column using a 4-min gradient elution consisting of mobile phase A (0.1% formic acid in water) and mobile phase B (0.1% formic acid in acetonitrile), at a flow rate of 0.4 mL/min. Ceritinib and the internal standard ([13C6]ceritinib) were monitored using multiple reaction monitoring mode under positive electrospray ionization. The lower limit of quantitation (LLOQ) was 1 nM of ceritinib in plasma. The calibration curve was linear over ceritinib concentration range of 1–2000 nM in plasma. The intra- and inter-day precision and accuracy were within the generally accepted criteria for bioanalytical method (<15%). The method was successfully applied to assess ceritinib brain tumor penetration, as assessed by the unbound drug brain concentration to unbound drug plasma concentration ratio, in patients with brain tumors. |
| first_indexed | 2024-12-14T18:49:22Z |
| format | Article |
| id | doaj.art-b9329cb85ffd4998b41cf930a1abd890 |
| institution | Directory Open Access Journal |
| issn | 2095-1779 |
| language | English |
| last_indexed | 2024-12-14T18:49:22Z |
| publishDate | 2018-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj.art-b9329cb85ffd4998b41cf930a1abd8902022-12-21T22:51:19ZengElsevierJournal of Pharmaceutical Analysis2095-17792018-02-0181202610.1016/j.jpha.2017.07.007A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumorXun Bao0Jianmei Wu1Nader Sanai2Jing Li3Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USAKarmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USABarrow Neurological Institute, St. Joseph's Hospital&Medical Center, Phoenix, AZ 85013, USAKarmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USAA rapid, sensitive, and robust reversed-phase liquid chromatography with tandem mass spectrometry method was developed and validated for the determination of total and unbound ceritinib, a second-generation ALK inhibitor, in patient plasma and brain tumor tissue samples. Sample preparation involved simple protein precipitation with acetonitrile. Chromatographic separation was achieved on a Waters ACQUITY UPLC BEH C18 column using a 4-min gradient elution consisting of mobile phase A (0.1% formic acid in water) and mobile phase B (0.1% formic acid in acetonitrile), at a flow rate of 0.4 mL/min. Ceritinib and the internal standard ([13C6]ceritinib) were monitored using multiple reaction monitoring mode under positive electrospray ionization. The lower limit of quantitation (LLOQ) was 1 nM of ceritinib in plasma. The calibration curve was linear over ceritinib concentration range of 1–2000 nM in plasma. The intra- and inter-day precision and accuracy were within the generally accepted criteria for bioanalytical method (<15%). The method was successfully applied to assess ceritinib brain tumor penetration, as assessed by the unbound drug brain concentration to unbound drug plasma concentration ratio, in patients with brain tumors.http://www.sciencedirect.com/science/article/pii/S2095177917300953CeritinibReversed-phase liquid chromatography with tandem mass spectrometry (LC–MS/MS)Fraction unbound in plasmaFraction unbound in brain tissueBrain tumor penetrationUnbound brain-to-plasma partition coefficient |
| spellingShingle | Xun Bao Jianmei Wu Nader Sanai Jing Li A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor Journal of Pharmaceutical Analysis Ceritinib Reversed-phase liquid chromatography with tandem mass spectrometry (LC–MS/MS) Fraction unbound in plasma Fraction unbound in brain tissue Brain tumor penetration Unbound brain-to-plasma partition coefficient |
| title | A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor |
| title_full | A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor |
| title_fullStr | A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor |
| title_full_unstemmed | A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor |
| title_short | A liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor |
| title_sort | liquid chromatography with tandem mass spectrometry method for quantitating total and unbound ceritinib in patient plasma and brain tumor |
| topic | Ceritinib Reversed-phase liquid chromatography with tandem mass spectrometry (LC–MS/MS) Fraction unbound in plasma Fraction unbound in brain tissue Brain tumor penetration Unbound brain-to-plasma partition coefficient |
| url | http://www.sciencedirect.com/science/article/pii/S2095177917300953 |
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