Development and validation of an LC-MS/MS method for simultaneous determination of SH-1028, an irreversible third-generation EGFR TKI, and two of its metabolites in human plasma : application in clinical pharmacokinetics
SH-1028 is a novel, potent, and highly selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) developed for the treatment of T790M Mutation-positive non-small cell lung cancer (NSCLC). The objective was to develop an LC-MS/MS method for the simultaneous determination of SH-1028 and its metabolites, Imp2 and Imp3, in human plasma.The plasma samples were extracted through protein precipitation with acetonitrile on wet ice conditions. A rapid, sensitive, and specific method was developed and successfully applied to evaluate the pharmacokinetic (PK) properties of SH-1028 in patients with advanced NSCLC following single and multiple doses of SH-1028 (60 mg).After single-dose administration, the Cmax of SH-1028, Imp2, and Imp3 was 11.2, 50.2, and 7.99 ng/mL, respectively. The mean AUC0-24 h was 138, 602, and 76.7 h*ng/mL, respectively. And the terminal half-life time was 19.9, 14.4, and 26.1 h, respectively. After multiple-dose administration, SH-1028 exhibited a slight accumulation, with a mean accumulation ratio (RAUC) of 2.00.The study assessed the PK properties of SH-1028 following single and multiple doses in patients with advanced NSCLC and would provide meaningful information for the further development of SH-1028.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:53 |
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| Enthalten in: |
Xenobiotica; the fate of foreign compounds in biological systems - 53(2023), 2 vom: 10. Feb., Seite 84-92 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Sufeng [VerfasserIn] |
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| Links: |
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| Themen: |
EC 2.7.10.1 |
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| Anmerkungen: |
Date Completed 12.05.2023 Date Revised 12.05.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/00498254.2023.2183367 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM353274984 |
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| 245 | 1 | 0 | |a Development and validation of an LC-MS/MS method for simultaneous determination of SH-1028, an irreversible third-generation EGFR TKI, and two of its metabolites in human plasma |b application in clinical pharmacokinetics |
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| 500 | |a Date Revised 12.05.2023 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a SH-1028 is a novel, potent, and highly selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) developed for the treatment of T790M Mutation-positive non-small cell lung cancer (NSCLC). The objective was to develop an LC-MS/MS method for the simultaneous determination of SH-1028 and its metabolites, Imp2 and Imp3, in human plasma.The plasma samples were extracted through protein precipitation with acetonitrile on wet ice conditions. A rapid, sensitive, and specific method was developed and successfully applied to evaluate the pharmacokinetic (PK) properties of SH-1028 in patients with advanced NSCLC following single and multiple doses of SH-1028 (60 mg).After single-dose administration, the Cmax of SH-1028, Imp2, and Imp3 was 11.2, 50.2, and 7.99 ng/mL, respectively. The mean AUC0-24 h was 138, 602, and 76.7 h*ng/mL, respectively. And the terminal half-life time was 19.9, 14.4, and 26.1 h, respectively. After multiple-dose administration, SH-1028 exhibited a slight accumulation, with a mean accumulation ratio (RAUC) of 2.00.The study assessed the PK properties of SH-1028 following single and multiple doses in patients with advanced NSCLC and would provide meaningful information for the further development of SH-1028 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a EGFR-TKIs | |
| 650 | 4 | |a LC-MS/MS | |
| 650 | 4 | |a SH-1028 | |
| 650 | 4 | |a human plasma | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 7 | |a EGFR protein, human |2 NLM | |
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| 650 | 7 | |a ErbB Receptors |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 700 | 1 | |a Sha, Bijun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yuqing |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhiqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xian |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Luwei |e verfasserin |4 aut | |
| 700 | 1 | |a Shao, Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xijing |e verfasserin |4 aut | |
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