Determination of Trantinterol Enantiomers in Human Plasma by High‐Performance Liquid Chromatography – Tandem Mass Spectrometry Using Vancomycin Chiral Stationary Phase and Solid Phase Extraction and Stereoselective Pharmacokinetic Application

Abstract

A sensitive and enantioselective vancomycin chiral stationary phase high-performance liquid chromatography-tandem mass spectrometry method was developed for the determination of trantinterol enantiomers in human plasma. Baseline resolution was achieved using the vancomycin chiral stationary phase known as Chirobiotic V with polar ionic mobile phase consisting of acetonitrile-methanol (60:40, v/v) containing 0.01% ammonia and 0.02% acetic acid at a flow rate of 1.0 mL/min. Waters Oasis HLB C18 solid phase extraction cartridges were used in the sample preparation of trantinterol samples from plasma. The detection was performed on a triple-quadrupole tandem mass spectrometer by multiple reaction monitoring mode via electrospray ionization. The calibration curve was linear in a concentration range from 0.0606 to 30.3 ng/mL in plasma, with the lower limit of quantification of 0.0606 ng/mL. The intra- and interday precision (relative standard deviation) values were within 9.7% and the accuracy (relative error) was from -6.6 to 7.2% at all quality control levels. The method was successfully applied to a study of stereoselective pharmacokinetics in human.

Pharmacology and Therapeutics of Bronchodilators Revisited

“…This finding contrasts with the documentation that other (S)-enantiomers are effectively inert at the b 2 -AR (Jacobson et al, 2018). However, it was found that the concentration of (S)-trantinterol was higher than that of (R)-trantinterol, implying the stereoselective disposition of trantinterol enantiomers in humans (Qin et al, 2015). This drug is currently being evaluated in phase III clinical trials in China for the treatment of patients with asthma.…”

Enantioselective Liquid Chromatographic Separations Using Macrocyclic Glycopeptide-Based Chiral Selectors

“…Separation of enantiomers of trantinterol was carried out on Chirobiotic TM V using MeOH/MeCN/AcOH/NH 4 OH mobile phases [ 26 ]. The optimized method was applied to determine the concentration of enantiomers in human plasma.…”

Chirality of β2-agonists. An overview of pharmacological activity, stereoselective analysis, and synthesis

“…Enantioseparation of a new β 2 -agonist trantinterol was achieved on the Chirobiotic V column with a mobile phase consisting of acetonitrile-methanol (60:40, v/v) containing 0.05% ammonia and 0.1% acetic acid [104]. The LC-MS/MS method based on this separation condition was applied to a study of stereoselective pharmacokinetics of trantinterol in rats and humans [105].…”