Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS method
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 concentra...
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2021-09-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2021-0024 |
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| author | Zuo Sai-Jie Cheng Xiao-Liang Liu Dong-Zheng Feng Wei-Yi Cao Yong-Xiao Zhang San-Qi |
| author_facet | Zuo Sai-Jie Cheng Xiao-Liang Liu Dong-Zheng Feng Wei-Yi Cao Yong-Xiao Zhang San-Qi |
| author_sort | Zuo Sai-Jie |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2e95e5206504479781f5ebd219d9c593 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2021-09-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-2e95e5206504479781f5ebd219d9c5932025-02-02T15:46:50ZengSciendoActa Pharmaceutica1846-95582021-09-0171341542810.2478/acph-2021-0024acph-2021-0024Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS methodZuo Sai-Jie0Cheng Xiao-Liang1Liu Dong-Zheng2Feng Wei-Yi3Cao Yong-Xiao4Zhang San-Qi5School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei PRChinaDepartment of Pharmacy, The First Affiliated Hospital, Xi′an Jiaotong University, Xi′an, Shaanxi, 710061 PRChinaDepartment of Pharmacology, School of Basic Medical Science, Xi′an Jiaotong University, Xi′an, Shaanxi, 710061 PRChinaDepartment of Pharmacy, The First Affiliated Hospital, Xi′an Jiaotong University, Xi′an, Shaanxi, 710061 PRChinaDepartment of Pharmacology, School of Basic Medical Science, Xi′an Jiaotong University, Xi′an, Shaanxi, 710061 PRChinaDepartment of Pharmacology, School of Basic Medical Science, Xi′an Jiaotong University, Xi′an, Shaanxi, 710061 PRChina1-(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.https://doi.org/10.2478/acph-2021-0024zcj14epidermal growth factor receptor inhibitorlc-ms/mspharmacokineticsbioavailability |
| spellingShingle | Zuo Sai-Jie Cheng Xiao-Liang Liu Dong-Zheng Feng Wei-Yi Cao Yong-Xiao Zhang San-Qi Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS method Acta Pharmaceutica zcj14 epidermal growth factor receptor inhibitor lc-ms/ms pharmacokinetics bioavailability |
| title | Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS method |
| title_full | Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS method |
| title_fullStr | Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS method |
| title_full_unstemmed | Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS method |
| title_short | Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS method |
| title_sort | quantitative analysis and pharmacokinetic study of a novel diarylurea egfr inhibitor zcj14 in rat plasma using a validated lc ms ms method |
| topic | zcj14 epidermal growth factor receptor inhibitor lc-ms/ms pharmacokinetics bioavailability |
| url | https://doi.org/10.2478/acph-2021-0024 |
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