LC-MS/MS METHOD FOR SIMULTANEOUS QUANTIFICATION OF SERIES OF AMINOPROPAN-2-OL DERIVATIVES-APPLICATION TO IN VIVO PHARMACOKINETIC STUDY

Abstract

A selective and a sensitive liquid chromatography-tandem mass spectrometry method for simultaneous determination of new aminopropan-2-ol derivatives with β-adrenolytic activity briefly called 2F109-(2RS)-1-(1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol, ANBL-(2RS)-1-(5-methoxy-1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol, and TWo8-(2RS)-1-(7-methoxy-1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol in rat serum was developed. The pharmacokinetics of 2F109, ANBL, and TWo8 in rats was performed following a single intravenous or intragastric administration of studied substances at a dose of 1 mg/kg. The work-up procedure involves a liquid–liquid extraction step using ethyl acetate and followed by gradient chromatography on a reversed-phase XBridge C18 column. Quantification analysis was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique, operating in the positive ionization and selected reaction monitoring mode. The limit of detection was found to be 0.5 ng/mL, the limit of quantification was 2 ng/mL. The intra-day and inter-day precision for quality control samples ranged from 6.3% to 14.2%, and intra-day and inter-day accuracy ranged from −0.8% to 10%. The terminal half-lives for 2F109, ANBL, and TWo8 after intravenous administration were 39.2 min, 262.3 min, and 169.4 min, respectively. The absolute bioavailability for 2F109, ANBL, and TWo8 were 40.2, 26.2, and 14.7%, respectively.