Determination of the enantiomers of salbutamol and its 4-O-sulphate metabolites in biological matrices by chiral liquid chromatography tandem mass spectrometry

Rapid Commun Mass Spectrom. 1998;12(23):1899-910. doi: 10.1002/(SICI)1097-0231(19981215)12:23<1899::AID-RCM417>3.0.CO;2-I.


Sensitive, mass spectrometry based bioanalytical methods are described for the determination of the R- and S-enantiomers of the beta-agonist salbutamol (albuterol) and its 4-O-sulphate metabolite in human plasma and urine. In both methods samples are prepared by 96 well format solid phase extraction using a custom built robotic system. Extracts are then analysed by liquid chromatography tandem mass spectrometry (LC-MS/MS) using a teicoplanin-based chiral stationary phase and selected reaction monitoring. The methods are accurate (bias < +/- 10%), precise (%CV < 11%) and sensitive, providing lower limits of quantitation (LLoQ) in plasma of 100 pg/mL and 5 ng/mL for the enantiomers of salbutamol and its 4-O-sulphate metabolite, respectively. By restricting the chiral method for plasma to the enantiomers of salbutamol only, it was possible to revalidate at an improved LLoQ of 25 pg/mL. A high throughout LC-MS/MS method has also been developed for racemic salbutamol only, which uses a similar extraction procedure but a conventional C8 column. The method has a reduced analysis time of three minutes per sample and using a high sensitivity, triple quadrupole mass spectrometer provides an LLoQ of 5 pg/mL based on extraction of 0.5 mL of plasma.

MeSH terms

  • Adrenergic beta-Agonists / analysis*
  • Adrenergic beta-Agonists / blood
  • Adrenergic beta-Agonists / pharmacokinetics
  • Albuterol / analysis*
  • Albuterol / blood
  • Albuterol / pharmacokinetics
  • Chromatography, Liquid
  • Humans
  • Indicators and Reagents
  • Mass Spectrometry
  • Quality Control
  • Stereoisomerism
  • Sulfates / analysis
  • Sulfates / blood


  • Adrenergic beta-Agonists
  • Indicators and Reagents
  • Sulfates
  • Albuterol