Chapter 5 - Application of chromatographic techniques for therapeutic drug monitoring

Abstract

Immunoassays are widely used for therapeutic drug monitoring because such assays can be easily adopted on automated chemistry analyzers and specimens can be analyzed in a batch. After programming the instrument, a technologist can walk away and later release the results. However, immunoassays are subjected to interferences not only from endogenous factors such as high bilirubin or paraprotein but also from metabolites of the drug or even structurally similar molecules. However, chromatographic methods especially liquid chromatography combined with mass spectrometry (LC–MS/MS) are more sensitive and specific compared to most immunoassays. Immunosuppressants require routine monitoring in organ transplant patients but immunoassays for cyclosporine, tacrolimus, sirolimus and everolimus and to some less extent mycophenolic acid suffer from significant interference from drug metabolites. Therefore, LC–MS/MS methods are considered as gold standard. In addition, more drugs which are less commonly monitored, immunoassays may not be commercially available. For such drugs chromatographic methods are the only available methods for therapeutic drug monitoring.