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

Synthesis and biological evaluation of 2-fluoro and 3-trifluoromethyl-phenyl-piperazinylalkyl derivatives of 1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione as potential antidepressant agents

“…The disappearance of the parent compound was monitored by calculating the percentage of each compound remaining relative to 0 min and this was plotted against the incubation time. Currently, commercially available human liver microsomes (HLM) have been the most widely used in vitro models for metabolic stability studies 49 . Compounds 9 and 20 were selected for in vitro metabolic stability assays.…”

New Arylpiperazinylalkyl Derivatives of 8‐Alkoxy‐purine‐2,6‐dione and Dihydro[1,3]oxazolo[2,3‐f]purinedione Targeting the Serotonin 5‐HT1A/5‐HT2A/5‐HT7 and Dopamine D2 Receptors

“…The tests without NADPH-regenerating system were conducted in parallel. All probes were done in duplicate [45,46].…”

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

“…The mobile phase consisted of 40% ethanol and 60% hexane, and the flow rate was 0.8 mL/min, with a post column flow splitter (1:1) to divert 0.4 mL/min to waste. The injection volume was 10 L and the column temperature was maintained at 20 • C. Mass spectrometric detection was carried out, using the same source and mass spectrometer conditions as previously reported [2], on an Applied Biosystem 4000 QTRAP ® hybrid triple quadrupole/linear ion trap (QqQ LIT ) mass spectrometer (Applied Biosystems/MDS Sciex, Foster City, CA, USA) equipped with an electrospray ionization (ESI) source. The 4000 QTrap was calibrated semiannually using polypropylene glycol (PPG) for mass accuracy.…”

“…1-[4-(2-Methoxyethyl) phenoxy]-3-[[2-(2-methoxyphenoxy) ethyl]amino]-2-propanol hydrochloride (TJ0711 HCl) was synthesized by us as a new vasodilatory ␤-blocker for hypertension and other related syndromes [1,2]. As stated previously, TJ0711 possesses a single chiral center and the two enantiomers exhibited differing pharmacokinetic properties in preclinical pharmacokinetic studies [3].…”

“…In 2011, we developed and validated an achiral ultraperformance liquid chromatography-multiple reaction monitoring-information dependent acquisition-enhanced product ion (UPLC-MRM-IDA-EPI) method for the simultaneous determination of racemic TJ0711 HCl as well as its metabolites [2]. The racemic mixture underwent a rapid in vitro phase I metabolism mediated by human liver microsomes (HLM) and a number of metabolites including demethylated and/or hydroxylated products were identified during in vitro incubations.…”