AbstractA 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 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.

2017-11-01·Journal of Separation Science3区 · 化学

Enantioselective determination of 1‐[4‐(2‐methoxyethyl)phenoxy]‐3‐[2‐(2‐methoxyphenoxy)ethylamino]‐2‐propanol hydrochloride, a novel antihypertensive agent, in rat plasma and tissues by liquid chromatography–tandem mass spectrometry

3区 · 化学

Article

作者: He, Sijie ; Guan, Yeli ; Zhu, Wenwen ; Wu, Sanlan ; Si, Luqin ; Huang, Jiangeng ; Li, Gao

AbstractEnantioselective biodistribution studies of 1‐[4‐(2‐methoxyethyl)phenoxy]‐3‐[2‐(2‐methoxyphenoxy)ethylamino]‐2‐propanol hydrochloride (TJ0711), a novel antihypertensive agent, require the accurate and precise quantification of each TJ0711 enantiomer in biological fluids and tissues. Here we report a simple and sensitive liquid chromatography with tandem mass spectrometry method for simultaneous determination of (R)‐TJ0711 and (S)‐TJ0711 in rat plasma and tissue samples using protein precipitation. The influence of column type, temperature, mobile phase composition, and flow rate on the retention and enantioselectivity was evaluated. The separation of the TJ0711 enantiomers was ultimately achieved on a SUMICHIRAL OA‐2500 column in 15 min using isocratic elution with ethanol/hexane (40:60) at a flow rate of 0.8 mL/min. Good linearities of spiked analyte concentration from 5 to 2000 ng/mL were achieved and the correlation coefficients (R) were greater than 0.99. The intra‐ and inter‐day accuracy and precision for both analytes were <15% at all concentration levels, and the extraction recoveries were consistent among the five quality control concentrations. This assay was successfully applied to quantify plasma and tissue concentrations of TJ0711 enantiomers in a preclinical study.

2015-06-01·Journal of Separation Science3区 · 化学

Liquid Chromatography

3区 · 化学

Article

作者: Li, Gao ; Cao, Peng ; Xu, Xiaolong ; Si, Luqin ; Zhang, Chenghao ; Hu, Lei ; Lv, Zhenhua ; Huang, Jiangeng

TJ0711 (1-[4-(2-methoxyethyl)phenoxy]-3-[2-(2-methoxyphenoxy)ethylamino]-2-propanol) is a novel β-adrenoreceptor blocker with vasodilating activity. The aim of this study was to investigate the in vitro metabolic properties of TJ0711 from both qualitative and quantitative aspects using mouse, rat, dog, and human liver microsomes as well as rat hepatocytes. Two modern liquid chromatography with tandem mass spectrometry systems, ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and ultra fast liquid chromatography with quadrupole linear ion trap mass spectrometry, were utilized for the analysis. To better characterize the metabolic pathways of TJ0711, two major metabolites were incubated under the same conditions as that for TJ0711. TJ0711 was extensively metabolized in vitro, and a total of 34 metabolites, including 19 phase I and 15 phase II metabolites, were identified. Similar metabolite profiles were observed among species, and demethylation, hydroxylation, carboxylic acid formation, and glucuronidation were proposed as the major metabolic routes. Significant interspecies differences were observed in the metabolic stability studies of TJ0711. Furthermore, gender differences were significant in mice, rats, and dogs, but were negligible in humans. The valuable information provided in this work will be useful in planning and interpreting further pharmacokinetic, in vivo metabolism and toxicological studies of this novel β-blocker.

100 项与 TJ-0711 相关的药物交易

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