<abstract xmlns="http://www.w3.org/1999/xhtml">1-(4-(Pyrrolidin-1-yl-methyl)phenyl)-3-(4-((3-(trifluoromethyl) phenyl)amino)quinazolin-6-yl)urea (ZCJ14), a novel epidermal growth factor receptor (EGFR) inhibitor, with diarylurea moiety, displays anticancer effect. In the present study, an LCMS/MS method was established to determine the concentration of ZCJ14 in rat plasma. Furthermore, the method was applied to investigate the pharmacokinetic characteristics of ZCJ14. Chromatographic separation of ZCJ14 and internal standard (IS) [1-phenyl-3-(4-((3-(trifluoromethyl)phenyl)amino) quinazolin-6-yl)urea] was accomplished by gradient elution using the Kromasil C18 column. The selected reaction monitoring transitions were performed at <italic>m</italic>/<italic>z</italic> 507.24→436.18 and 424.13→330.96 for ZCJ14 and IS, resp. The established method was linear over the concentration range of 10–1000 ng mL−1. The intra- and inter-day precisions were &lt; 11.0 % (except for <italic>LLOQ</italic> which was up to 14.3 %) and the respective accuracies were within the range of 87.5–99.0 %. The extraction recovery and matrix effect were within the range of 88.4–104.5 % and 87.3–109.9 %, resp. ZCJ14 was stable under all storage conditions. The validated method was successfully applied to the pharmacokinetic study of ZCJ14 in rats, and the pharmacokinetic parameters have been determined. The oral bioavailability of ZCJ14 was found to be 46.1 %. Overall, this accurate and reliable quantification method might be useful for other diarylurea moiety-containing drugs.</abstract>

1-(4-(Pyrrolidin-1-yl-methyl)phenyl)-3-(4-((3-(trifluoromethyl) phenyl)amino)quinazolin-6-yl)urea (ZCJ14), a novel epidermal growth factor receptor (EGFR) inhibitor, with diarylurea moiety, displays anticancer effect. In the present study, an LCMS/MS method was established to determine the concentration of ZCJ14 in rat plasma. Furthermore, the method was applied to investigate the pharmacokinetic characteristics of ZCJ14. Chromatographic separation of ZCJ14 and internal standard (IS) [1-phenyl-3-(4-((3-(trifluoromethyl)phenyl)amino) quinazolin-6-yl)urea] was accomplished by gradient elution using the Kromasil C18 column. The selected reaction monitoring transitions were performed at m/z 507.24→436.18 and 424.13→330.96 for ZCJ14 and IS, resp. The established method was linear over the concentration range of 10–1000 ng mL−1. The intra- and inter-day precisions were < 11.0 % (except for LLOQ which was up to 14.3 %) and the respective accuracies were within the range of 87.5–99.0 %. The extraction recovery and matrix effect were within the range of 88.4–104.5 % and 87.3–109.9 %, resp. ZCJ14 was stable under all storage conditions. The validated method was successfully applied to the pharmacokinetic study of ZCJ14 in rats, and the pharmacokinetic parameters have been determined. The oral bioavailability of ZCJ14 was found to be 46.1 %. Overall, this accurate and reliable quantification method might be useful for other diarylurea moiety-containing drugs.

Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS method

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

1-(4-(Pyrrolidin-1-yl-methyl)phenyl)-3-(4-((3-(trifluoromethyl) phenyl)amino)quinazolin-6-yl)urea (ZCJ14), a novel epidermal growth factor receptor (EGFR)...

Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS method

Online veröffentlicht: 31. Dez. 2020

Seitenbereich: 415 - 428

Akzeptiert: 04. Aug. 2020

DOI: https://doi.org/10.2478/acph-2021-0024

Schlüsselwörter
ZCJ14, epidermal growth factor receptor inhibitor, LC-MS/MS, pharmacokinetics, bioavailability

© 2021 Sai-Jie Zuo et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS method

Online veröffentlicht: 31. Dez. 2020

Seitenbereich: 415 - 428

Akzeptiert: 04. Aug. 2020

DOI: https://doi.org/10.2478/acph-2021-0024

SchlüsselwörterZCJ14, epidermal growth factor receptor inhibitor, LC-MS/MS, pharmacokinetics, bioavailability

© 2021 Sai-Jie Zuo et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Schlüsselwörter
ZCJ14, epidermal growth factor receptor inhibitor, LC-MS/MS, pharmacokinetics, bioavailability