Determination of TJ0711 hydrochloride in rat plasma by high performance liquid chromatography with fluorescence detection and its application to pharmacokinetics

In vitro metabolic stability and metabolite profiling of TJ0711 hydrochloride, a newly developed vasodilatory β-blocker, using a liquid chromatography–tandem mass spectrometry method

“…Compared to UV and fluorescence detectors, the assay sensitivity for the quantitation of TJ0711 HCl has been enhanced by at least 100-fold using the LC-MS/MS method [11,20]. In this study, the [M+H] + → 252 transition was used for the parent compound quantification.…”

“…1), was synthesized as a new vasodilatory ␤-blocker for hypertension and other related syndromes [10]. Our previous preclinical pharmacokinetic results showed that a rapid in vivo clearance (half life <30 min) was observed in rats following a single intravenous dose of TJ0711 hydrochloride (TJ0711 HCl) [11]. One plausible explanation for the fast elimination of TJ0711 HCl is that it might undergo an extensive metabolism in rat liver.…”

In vitro enantioselective metabolism of TJ0711 hydrochloride by human liver microsomes using a novel chiral liquid chromatography–tandem mass spectrometry method

“…These LLOQ values are lower than those obtained from ultraviolet or fluorescence detection [3,11], but they are higher than those reported by a UPLC-MS/MS method [2]. Linearity was determined with the use of a weighting factor.…”

“…A liquid-liquid extraction (LLE) method using ethyl acetate has been reported for plasma sample clean-up [11], however, this method included multiple time-consuming procedures, and sample throughput was therefore greatly reduced. Recently, we developed a simple deproteinized procedure for in vitro metabolic incubation samples [2].…”

Accurate determination of a novel vasodilatory β‐blocker TJ0711 using LC‐MS/MS: Resolution of an isobaric metabolite interference in dog plasma

“…The LLOQ was determined as 0.5 ng/mL, with an ideal signal-to-noise ratio (>20) and acceptable precision and accuracy (Table 1), which was sufficiently sensitive for the quantification and pharmacokinetic analysis of TJ0711 in dog plasma. This method offered significantly higher sensitivity and broader dynamic range (1000-fold) compared with our previous methods (Fan et al, 2010;Huang et al, 2011Huang et al, , 2012Sun et al, 2009).…”