ABSTRACT
Quantitative mass spectrometry coupled with liquid chromatography has become the most widely used bioanalytical technique today. Its pre-eminence has arisen following the introduction of the robust and sensitive atmospheric pressure ionisation (API) techniques of electrospray ionisation (ESI) and atmospheric pressure chemical ionisation (APCI). These API techniques have allowed instruments to run for long periods of time with less maintenance from highly skilled operators. The dominance of API is such that there are few, if any, examples of the other ionisation methods such as EI, CI, and fast atom bombardment (FAB) present in the bioanalytical laboratory except when coupled to gas chromatography (GC). The second reason for this dramatic change has been the excellent selectivity of selected ion monitoring (SIM) of single-stage analysers and, more particularly, of selected reaction monitoring (SRM) of triple quadrupole instruments. The selectivity of these scan modes has dramatically reduced the time required to develop methods because endogenous components that may elute closely to the compound of interest are not detected in this mode of operation. However, the reduction in the amount of sample clean up that this selectivity provides may have a detrimental effect on the procedure as matrix effects can cause variable instrumental responses throughout the assay, leading to poor results.
