Application of liquid chromatography—Tandem mass spectrometry method for the analysis of new nonselective β‐adrenergic blocker 1‐(1‐H‐indol‐4‐yloxy)‐3‐{[2‐(2‐methoxy phenoxy)ethylo]amino}propan‐2‐ol (2F109) in rat plasma

Abstract

A sensitive and specific liquid chromatography electrospray ionization-tandem mass spectrometry method for the enantioselective determination of the novel beta-adrenolytic compound, 1-(1-H-indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethylo]amino} propan-2-ol, in rat plasma has been developed and validated. Chromatography was performed on a reversed-phase Chiralcel OD-RH analytical column (150x4.6 mm, 5 microm, Daicel Chemical Industries, Tokyo, Japan) with isocratic elution using a mobile phase containing acetonitrile and water with 0.01% formic acid. Detection was achieved by an Applied Biosystems MDS Sciex (Concord, Ontario, Canada) API 2000 triple quadrupole mass spectrometer. Electrospray ionization (ESI) was used for ion production. The limit of detection in the MRM mode was found to be 1.25 ng/ml. The limit of quantification of both enantiomers was 2.5 ng/ml. The precision and accuracy for both intra- and inter-day determination of 2F109 enantiomers ranged from 2.6 to 12% and from 89.1 to 107.1%. This analytical method allowed us to carry out pharmacokinetic studies in rats. Our findings demonstrate that 2F109 shows stereoselective disposition in rat plasma after i.v. administration. The terminal half-lives of (+)-(R)-2F109 and (-)-(S)-2F109 were 33.5 and 42.6 min, respectively. The AUC0-inf of (+)-(R)-2F109 exceeded that of (-)-(S)-2F109.