Determination of Albuterol Enantiomers in Animal Tissue Matrices by LC–MS/MS: Application in Therapeutic Myoanabolic Studies

Albuterol (salbutamol) is a widely used medication in respiratory disease including asthma and chronic obstructive airways disease; however, like other beta2-agonists, it also exerts some extrapulmonary effects on muscle and fat. Surprisingly, there have been relatively few reports of albuterol tissue distribution, and the distribution of individual albuterol enantiomers into tissue has not been reported. The method presented here explores the use of an HPLC tandem mass spectrometry (LC–MS/MS) system (LTQ Orbitrap hybrid mass spectrometer) with deuterated standard and solid-phase extraction to determine low levels of albuterol enantiomers in tissue. The lower limit of quantification (LLOQ) was 0.156 ng g⁻¹, with a precision RSD <15% for both enantiomers. The assay was linear over the calibration range of LLOQ-10.0 ng g⁻¹ in muscle tissue (r ² > 0.98). The assay was successfully applied to pharmacokinetic studies in rats and mice. By utilizing a deuterated internal standard and LC–MS/MS detection, this assay can be used to measure albuterol enantiomers in muscle tissue. This assay has also identified that albuterol uptake appears to be stereoselective, and enantioselective assays are clearly warranted for myoanabolic studies involving administration of racemic-albuterol.