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Development of a sensitive UHPLC–MS/MS method for the pharmacokinetics study of a novel tyrosine kinase inhibitors, 1‐[4‐(4‐{5‐Chloro‐4‐[2‐(propane‐2‐sulfonyl)‐phenylamino]‐pyrimidin‐2‐ylamino}‐phenyl)‐piperazin‐1‐yl]‐propenone in rats
Author(s) -
Wang Lin,
Li Xiangping,
Kong Ying,
Zhang Qiuyan,
Xie Honglei
Publication year - 2021
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.5059
Subject(s) - pharmacokinetics , chemistry , erlotinib , pharmacology , bioavailability , in vivo , repeatability , t790m , epidermal growth factor receptor , chromatography , gefitinib , receptor , medicine , biochemistry , biology , microbiology and biotechnology
Targeted inhibition of epidermal growth factor receptor has become an important means of chemotherapy for nonsmall cell lung cancer, breast cancer, pancreatic cancer, colon cancer and other malignant tumors. Although remarkable curative effects have been achieved in the past few decades, the emergence of drug resistance is a problem. Therefore, new inhibitors need to be developed. XHL‐31 is a new candidate with significant inhibitory activity against T790M and C797S mutations in vitro . In order to study the pharmacokinetics in vivo , a sensitive and efficient UHPLC–MS/MS method was developed for the determination of XHL‐31 in rat plasma in this study. The lower limit of quantitation of this method was 1 ng/ml and the linear range was 1–2,000 ng/ml. Method validation showed a high accuracy and precision, a high stability, a high recovery and repeatability. The method was successfully applied to the pharmacokinetic study of XHL‐31 in rats. The results indicated that there were significant gender differences in oral absorption and the absolute bioavailability of XHL‐31 in female rats were extremely low (<10%).