Accurate determination of a novel vasodilatory ß-blocker TJ0711 using LC-MS/MS: Resolution of an isobaric metabolite interference in dog plasma.
Biomed Chromatogr
; 32(6): e4196, 2018 Jun.
Article
em En
| MEDLINE
| ID: mdl-29357403
ABSTRACT
A rapid, robust and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for bioanalysis of TJ0711, a novel vasodilatory ß-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 C18 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.
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Base de dados:
MEDLINE
Assunto principal:
Cromatografia Líquida
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Fenoxipropanolaminas
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Espectrometria de Massas em Tandem
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article