Utility, promise, and limitations of liquid chromatography‐mass spectrometry‐based therapeutic drug monitoring in precision medicine

Abstract

Therapeutic drug monitoring (TDM) is typically referred to as the measurement of the concentration of drugs in patient blood. Although in the past, TDM was restricted to drugs with a narrow therapeutic range in order to avoid drug toxicity, TDM has recently become a major tool for precision medicine being applied to many more drugs. Through compensating for interindividual differences in a drug's pharmacokinetics, improved dosing of individual patients based on TDM ensures maximum drug effectiveness while minimizing side effects. This is especially relevant for individuals that present a particularly high intervariability in pharmacokinetics, such as newborns, or for critically/severely ill patients. In this article, we will review the applications for and limitations of TDM, discuss for which patients TDM is most beneficial and why, examine which techniques are being used for TDM, and demonstrate how mass spectrometry is increasingly becoming a reliable and convenient alternative for the TDM of different classes of drugs. We will also highlight the advances, challenges, and limitations of the existing repertoire of TDM methods and discuss future opportunities for TDM‐based precision medicine.

How the VALID Act could affect patient access to laboratory developed testing for therapeutic drug monitoring

“…When compared with LCMS, patient results for tacrolimus tended to be positively biased (up to 40 %), indicating potential active or inactive tacrolimus metabolites cross-reacting in the immunoassay [28] . Because of direct mass detection along with multiple quality measures, LCMS is far less prone to interference from structurally similar metabolites, reinforcing why LDT LCMS-based assays are the reference method for testing and essential for precision medicine [22] , [28] , [29] .…”

“…However, patient populations may be at risk of experiencing diminished access to critical laboratory testing if the VALID Act is passed as currently written. LCMS-based LDTs provide much-needed flexibility to safely adjust analytical parameters to meet the needs of highly specialized and delicate patient populations for fast and accurate TDM [22] . As the healthcare model continues to shift towards providing quality care through personalized medicine [29] , [30] , passing the VALID Act in its current form would be a step backward.…”

“…This is especially important when focusing on LCMS-based assays. LCMS testing requires significant scientific and clinical training to understand the complexities and nuances of assay development, validation and implementation, which only highly specialized laboratorians understand [22] .…”

Molecular prediction of clinical response to anti‐PD‐1/anti‐PD‐L1 immune checkpoint inhibitors: New perspectives for precision medicine and mass spectrometry‐based investigations

“…MS-based proteomics using liquid chromatography (LC)-ESI-MS/MS is often the gold standard for both targeted and untargeted assays and should be included in the pipeline of molecular pathology and molecular pharmacology tests for precision medicine. [69][70][71][72][73] Thus, the next section will focus on this approach.…”

Isolation of Antidepressants and Their Metabolites from Saliva Using Supported Liquid Extraction (SLE)

“…When trying to use saliva to analyze the levels of active substances for therapeutic drug monitoring (TDM), it is essential to have a standardized correlation between the concentration of a compound in the saliva and the blood [ 3 ]. Studies on the suitability of saliva as a diagnostic material for the determination of amitriptyline, a first-generation drug approved by the FDA in 1961 [ 4 ], were conducted in the 1970s and confirmed the existence of a correlation between the concentrations of the free fraction of amitriptyline in blood and saliva [ 5 , 6 ].…”