Enantioselective determination of trantinterol in rat plasma by ultra performance liquid chromatography–electrospray ionization mass spectrometry after derivatization

An ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for the determination of trantinterol enantiomers in rat plasma. Diphenhydramine was employed as the internal standard. The plasma samples were prepared using liquid–liquid extraction with n-hexane–dichloromethane–isopropanol (20:10:1, v/v/v) as the extractant. Trantinterol enantiomers after pre-column derivatization using diacetyl-l-tartaric anhydride (DATAAN) were separated on a C18 column using a gradient solvent programme. The mobile phase was composed of 3 mM ammonium acetate and acetonitrile. The detection was performed on a triple-quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI). Linear calibration curve for each enantiomer was obtained in the concentration range of 1–80 ng/mL, with limit of quantification (LOQ) of 1 ng/mL. The intra- and inter- precision (R.S.D.) values were below 9.6% and accuracy (R.E.) was from −2.4 to 6.2% at all quality control (QC) levels. The developed method was applied to the enantioselective pharmacokinetic study of trantinterol in rats.