Chiral separation of terbutaline by supercritical fluid chromatography with peaks purity determination by UPLC-MS and modelling for chiral recognition mechanism

Abstract: Background: Terbutaline is the drug of choice for asthma patients but it exist in racemic mixture. (R)-(-)-terbutaline is 200 times more active than (S)-(+)-terbutaline and it is not advisable to prescribe racmix xiture due to certain side effects of (S)-(+)-terbutaline. Therefore, fast, effective and reproducible separation method is the need of today. Results: Chiral separation was achieved on Chiralpak IE and Chiralpak IG columns (250 mm x 4.6 mm, 5 µm) using CO2-MeOH (60:40) with 0.2% triethylamine mobile phase. The flow was 1.0 mL/min with detection at 223 nm using a PDA detector. The values of retention, separation and resolution factors were in the range of 1.88 to 2.38, 1.14 to 1.26 and 0.91 to 1.17; with best separation with Chiralpak IE. The tailing factors and number of theoretical plates were in the range of 1.0 to 1.23 and 487 to 3699. The purity of the separated peaks was determined by UPLC-MS; indicating 100% purity of the peaks. The chiral recognition was determined by modeling with binding affinities -5.0 and -6.0 of S- and R-enantiomers; indicating S-enantiomers elution first followed by R-enantiomers. The major forces responsible for the chiral resolution were hydrogen bonding and π-π interactions. Conclusion: Due to the great demand for optically active pure drugs and high economic pressure on analytical techniques, the chiral separation of terbutaline was achieved on inexpensive supercritical fluid chromatography. The reported method may be used to prepare optically active pure terbutaline drugs (R-enantiomers) at a pilot scale.