Quantitation of salbutamol using micro-volume blood sampling–applications to exacerbations of pediatric asthma

Objectives: A novel gas chromatography-mass spectrometry (GC-MS) method has been developed to quantify salbutamol in micro-volumes (10 µL) of blood. A potential application is paediatric therapeutic dose monitoring (TDM) in acute severe asthma. Methods: At presentation, the children receive multiple doses of salbutamol (inhaled, nebulised and occasionally intravenous) but it is difficult to distinguish children who do not respond to treatment because of inadequate concentrations from those with toxicity, as symptoms are similar. A comparison was made between traditional dried blood spots (DBS) and the newly developed technique volumetric absorptive micro-sampling (VAMS), with specific investigation into the effect of drying time on analyte recovery. Results: For both sampling techniques, the final assay demonstrated good precision and accuracy across the concentration range tested (3–100 ng/mL), including both the normal therapeutic and toxic range. The method was developed to comply with FDA guidelines with precision and accuracy ≤15% for all concentrations, except the limit of quantification (5 ng/mL) where they were ≤20%. VAMS offered advantages in sampling ease and reduced GC-MS interference. The assay was successfully applied to the quantification of blood salbutamol concentrations in three healthy volunteers dosed with 1 mg salbutamol by inhalation. Conclusions: This demonstrated its potential for use in paediatric TDM studies, where in the acute situation considerably higher doses of salbutamol will have been administered. This is the first time that a TDM method for salbutamol has been carried out using VAMS and offers all the advantages provided by DBS, whilst eliminating the inherent sampling volume inaccuracies of traditional DBS collection.