Drug Bioanalysis by LC-MS: some pragmatic solutions to commonly occurring problems

The use of atmospheric pressure ionisation (API) LC-MS/MS has been very successful in drug bioanalysis. Despite this, many challenges, such as those presented by (a) sample matrix and mobile phase effects on ionisation, and (b) the determination of endogeneous analytes, remain. An aim was therefore set to investigate these problems with a view to attempting to find simple but effective solutions to them. It was found that late-eluting interferences could be dealt with by a change of mode of ionisation, that an order of magnitude improvement in limits of detection could be had by the post-column addition of an appropriate solvent and that ion enhancement could be induced by surfactants. In the determination of endogeneous analytes it was demonstrated that the use of non-matrix calibration standards and the use of a surrogate matrix were both useful approaches.