The emerging role of multiplex tandem mass spectrometry analysis for therapeutic drug monitoring and personalized medicine

Abstract

Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) constitutes now a key instrumental component of medical laboratory centres and has greatly facilitated the development of a considerable number of drugs assays for Therapeutic Drug Monitoring (TDM). The concept of TDM implies the measurement of concentrations of certain drugs in patients' blood, followed by dosage individualization based on patients' circulating exposure, targeting a pre-defined concentration range. This approach aims at increasing the likelihood of achieving therapeutic efficacy, while reducing the risk of toxicity. TDM can contribute to the rational individualization of critical drug treatments, notably antivirals, antibiotics, antiepileptics, psychotropic drugs and targeted anticancer agents, in the context of growing efforts towards personalized medicine. This article aims at reviewing the basic concepts, the role and the perspectives of evolution of TDM. It presents selected examples of clinical applications and gives some insights on how TDM is definitely benefiting from the tremendous development of LC-MS/MS techniques.

The Steps to Therapeutic Drug Monitoring: A Structured Approach Illustrated With Imatinib

“…Launching a TDM program for a given drug firstly requires developing and validating an appropriate analytical method, which implies technical resources and expertise that we will not address here (Decosterd et al, 2016). As soon as the method is applied to clinical samples, the first question coming when facing a TDM result is about the expectedness of the blood levels measured: "Is this concentration normal under the dosing regimen received by this patient with such individual characteristics?"…”

“…Nowadays, TDM measurements are still mostly performed in clinical chemistry labs, and the delivery of results is rarely associated with specialized pharmacological interpretation. However, recent developments in analytical technologies enable at present the measurement of an unprecedented number of drugs with excellent performances at affordable costs (Decosterd et al, 2016). In addition, recommendations for TDM have been expressed about hundreds of therapeutic agents, e.g.…”

Functionalization of nanostructured gold substrates with chiral chromophores for SERS applications: The case of 5‐Aza[5]helicene

“…, and τ 6 (C 4 -C 5 -C 6 -C 7 ) range. We started by considering a set of models differing in the conformation of the alkyl chain, as described by the dihedrals τ 1 and τ 6 (Figure 7).…”

“…This is a clinical field devoted to the monitoring of the blood level of different classes of drug molecules. In this framework, it is currently of interest to develop time‐ and cost‐effective techniques complementary to those currently adopted (mainly high‐performance liquid chromatography‐mass spectrometry and immunoassay) …”

“…In this framework, it is currently of interest to develop time-and cost-effective techniques complementary to those currently adopted (mainly high-performance liquid chromatography-mass spectrometry and immunoassay). [6][7][8][9] Widening the available techniques in therapeutic drug monitoring would lead to better pharmacological treatments, with a more effective drug dosage, which would improve the life quality of patients treated with drugs characterized by a narrow therapeutic index. 10 Raman spectroscopy is a powerful molecular probe, and the detection threshold characteristic of biomedical applications can be conveniently achieved by surface enhanced Raman scattering (SERS) spectroscopy.…”