Chiral analysis of bambuterol, its intermediate and active drug in human plasma by liquid chromatography–tandem mass spectrometry: Application to a pharmacokinetic study

•Chiral analysis of bambuterol, its intermediate and active drug in human plasma.•The method achieved the highest sensitivity and the fastest analysis speed.•Application to a clinical pharmacokinetics study of rac-bambuterol.•Stereoselective metabolism exists in the metabolic process of rac-bambuterol. A sensitive liquid chromatography-tandem mass spectrometry (LC–MS/MS) method has been developed for simultaneous chiral analysis of an antiasthma drug bambuterol, its key intermediate monocarbamate bambuterol and its active drug terbutaline in human plasma. All samples were extracted with ethyl acetate and separated on an Astec Chirobiotic T column under isocratic elution with a mobile phase consisting of methanol and water with the addition of 20mm ammonium acetate and 0.005% (v/v) formic acid at 0.6mL/min. The analytes were detected by a Xevo TQ-S tandem mass spectrometer with positive electrospray ionization in multiple reaction monitoring mode. The established method has high sensitivity with the lower limit of quantifications of 25.00pg/mL for bambuterol enantiomers, and 50.00pg/mL for monocarbamate bambuterol and terbutaline enantiomers, respectively. The calibration curves for bambuterol enantiomers were linear in the range of 25.00–2500pg/mL, and for monocarbamate bambuterol and terbutaline enantiomers were linear in the range of 50.00–5000pg/mL. The intra- and inter-day precisions were