Open AccessDetermination and pharmacokinetic study of AZD‐3759 in rat plasma by ultra performance liquid chromatography with triple quadrupole mass spectrometer
Author(s) -
Wu Qingjun,
Hua Ailian,
Sun Yaoguang,
Ma Chao,
Tian Wenxin,
Huang Chuan,
Yu Hanbo,
Jiao Peng,
Wang Shuanghu,
Tong Hongfeng,
Qiu Weiwen
Publication year - 2018
Publication title -
thoracic cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 28
eISSN - 1759-7714
pISSN - 1759-7706
DOI - 10.1111/1759-7714.12843
Subject(s) - medicine , formic acid , pharmacokinetics , chromatography , triple quadrupole mass spectrometer , mass spectrometry , electrospray ionization , analyte , high performance liquid chromatography , selected reaction monitoring , analytical chemistry (journal) , pharmacology , tandem mass spectrometry , chemistry
Background AZD‐3759 is a new, potent, oral, active central nervous system‐penetrant EGFR inhibitor. Despite promising clinical activity among patients pretreated and never treated with EGFR‐tyrosine kinase inhibitors, no time saving pharmacokinetic study method has been reported in an animal model. Methods Protein was precipitated with acetonitrile and then used for sample pre‐processing. A CORTECS BEH C18 column was used to separate the analytes at 40°C. Acetonitrile and water (containing 0.1% formic acid) were chosen as the mobile phase at a flow rate of 0.4 mL/min. The analytes were quantified by multiple reaction monitoring mode with positive electrospray ionization. Results The target fragment ions were m/z 460.38→141 for AZD‐3759 and m/z 285.1→193.1 for internal standard diazepam. The calibration curve exhibited good linearity for AZD‐3759 at a range of 1–500 ng/mL. The intra‐run and inter‐run precision variations were both < 8.22%. The recovery rate of AZD‐3759 from plasma was > 76.4%. Conclusion An accurate, simple ultra performance liquid chromatography with triple quadrupole mass spectrometer method was developed and validated to determine AZD‐3759 in rat plasma. Our validated method can be applied to the pharmacokinetic study of AZD‐3759 at an oral dosage of 10 mg/kg.