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

Abstract

Enantioselective 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.

Simultaneous Quantitation of a Novel α1/β1-Blocker TJ0711 and Its Two Metabolites in Dog Plasma Using LC-MS/MS and Its Application to a Pharmacokinetic Study after Intravenous Infusion

“…TJ0711∙HCl (1-[4-(2-methoxyethyl)phenoxy]-3-[2-(2-methoxyphenoxy)ethylamino]-2-propanol hydrochloride), a novel α 1 /β 1 adrenoceptor blocking agent with a ratio of 1:1 for α 1 /β 1 , is now under preclinical development (structure shown in Figure 1) [14,15,16,17,18]. As reported in previous research studies, TJ0711 could reduce diastolic blood pressure and systolic blood pressure in both spontaneously hypertensive rats and ouabain induced hypertensive rats following intravenous administration [19,20].…”

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

“…TJ0711, 1‐[4‐(2‐methoxyethyl) phenoxy]‐3‐{[2‐(2‐methoxyphenoxy)ethyl] amino}‐2‐propanol (structure shown in Figure ), is currently undergoing preclinical evaluation (He et al, ; Hu et al, ; Huang et al, ). TJ0711 has been found to be effective in the treatment of hypertension in rats by blocking α ‐ and β ‐adrenoceptors (Li, Qiu, Zhang, Chen, & Li, ).…”