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Accurate determination of a novel vasodilatory β ‐blocker TJ0711 using LC‐MS/MS: Resolution of an isobaric metabolite interference in dog plasma
Author(s) -
Hu Yang,
Zhu Wenwen,
Guan Yeli,
Wu Sanlan,
Zhang Xiaoyin,
Li Gao,
Si Luqin,
Huang Jiangeng
Publication year - 2018
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.4196
Subject(s) - chemistry , chromatography , analyte , isobaric process , pharmacokinetics , bioanalysis , metabolite , liquid chromatography–mass spectrometry , mass spectrometry , extraction (chemistry) , resolution (logic) , selected reaction monitoring , active metabolite , tandem mass spectrometry , pharmacology , medicine , biochemistry , physics , artificial intelligence , computer science , thermodynamics
A rapid, robust and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for bioanalysis of TJ0711, a novel vasodilatory β ‐blocker in dog plasma. This assay is able to chromatographically separate TJ0711 from its isobaric metabolite as well as glucuronide conjugates. Chromatographic separation was achieved on a Welch Ultimate‐XB C 18 column (2.1 × 100 mm, 3 μm). The analyte and internal standard (propranolol) were extracted from plasma by liquid–liquid extraction using ethyl acetate. The mass spectrometric detection was carried out in positive ion multiple reaction monitoring mode. Good linearity was obtained over the concentration range of 0.5–500 ng/mL ( r > 0.99) for TJ0711. Moreover, the method had good accuracy (RE ranging from −2.70 to −0.32%) and precision (RSD < 7.55%). TJ0711 was stable in dog plasma for at least 6 h at ambient temperature, for at least 30 days at −20°C and after three freeze–thaw cycles. This method was successfully applied to a preclinical pharmacokinetic study and the results demonstrated linear pharmacokinetics of TJ0711 over a dose range from 0.03 to 0.3 mg/kg. No significant gender differences were observed in TJ0711 plasma pharmacokinetic parameters.