Advances in antifungal drug measurement by liquid chromatography-mass spectrometry

Fungal infections, especially invasive types, have become a serious healthcare problem as the immunocompromised population increases. There are five main classes of antifungal drugs: polyenes, flucytosine, allylamines, azoles, and echinocandins. Therapeutic drug monitoring (TDM) is justified for flucytosine and triazoles due to their large inter- and intra-individual pharmacokinetic variability and their high tendency for drug-drug interactions. Available methods for measuring these drugs include bioassay, liquid chromatography and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The LC-MS/MS approach is preferred due to its superior analytic sensitivity and specificity. In this review, we highlight TDM methods by LC-MS/MS for these antifungal drugs searchable in PubMed by December 1, 2018. LC-MS/MS methods that were developed for other purposes such as pharmacokinetics or toxicokinetics were also included. We have critically analyzed these methods with an emphasis on sensitivity, specificity, simplicity, throughput and robustness.