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Original scientific paper

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

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

SAI-JIE ZUO orcid id orcid.org/0000-0001-7819-4069 ; School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, PR China
XIAO-LIANG CHENG orcid id orcid.org/0000-0001-7819-4069 ; Department of Pharmacy, The First Affiliated Hospital, Xian Jiaotong University, Xian, Shaanxi, 710061, PR China
DONG-ZHENG LIU orcid id orcid.org/0000-0001-7819-4069 ; Department of Pharmacology, School of Basic Medical Science, Xian Jiaotong University, Xian, Shaanxi, 710061, PR China
WEI-YI FENG orcid id orcid.org/0000-0001-7819-4069 ; Department of Pharmacy, The First Affiliated Hospital, Xian Jiaotong University, Xian, Shaanxi, 710061, PR China
YONG-XIAO CAO orcid id orcid.org/0000-0001-7819-4069 ; Department of Pharmacology, School of Basic Medical Science, Xian Jiaotong University, Xian, Shaanxi, 710061, PR China
SAN-QI ZHANG orcid id orcid.org/0000-0001-6371-0067 ; Department of Pharmacology, School of Basic Medical Science, Xian Jiaotong University, Xian, Shaanxi, 710061, PR China


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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 LC-MS/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.

Keywords

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

Hrčak ID:

242228

URI

https://hrcak.srce.hr/242228

Publication date:

30.9.2021.

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