Can Pharmacometabolomics and LC-HRMS develop a new Concept for Therapeutic Drug Monitoring?

Olof Beck

doi:10.17145/jab.15.008

Abstract

Therapeutic drug monitoring (TDM) is a concept for individualized drug dosing that was developed into clinical routine as a consequence of research findings on variable drug effects and analytical technology developments made in the 1950th and onwards, and founded the clinical pharmacology discipline (1,2). TDM in practice is about measuring a specific drug concentration in blood, serum or plasma, but may also include pharmacogenetic and pharmacodynamic investigations (3). For some time big hopes were put on pharmacogenetics to help explain inter-individual variability in drug response. It is now realized that variability may occur over time and relate to influences from both inborn as well as environmental factors, and that a more multifactorial approach is needed for complex biological systems (4). Examples of important use of TDM comprise treatment of epilepsy, infection, psychiatric disease and immunosuppression after transplantation (1,5,6). Analytical methods for TDM were using immunochemical, HPLC and GC techniques for long time, but this has recently, but slowly, been challenged by LC-MS techniques (7). One good example of this is methods for the immunosuppressive drugs tacrolimus, ciclosporin, sirolimus and everolimus (8,9). LC-MS methods have offered significant improvements in the quality of analytical method performance. It has been demonstrated that LC-MS offer improvement in accuracy, precision and cost-effectiveness, and also can be made robust. With the use of LC-MS in LC-tandem MS SRM mode multi-component methods can be constructed with unique combination of selectivity and sensitivity. Analytical method demands in TDM are set by the requirements of accuracy, cost-effectiveness, rapid reporting and robustness in a routine laboratory environment.

Highlights

TDM today Therapeutic drug monitoring (TDM) is a concept for individualized drug dosing that was developed into clinical routine as a consequence of research findings on variable drug effects and analytical technology developments made in the 1950th and onwards, and founded the clinical pharmacology discipline [1,2]
Pharmacometabolomics has been used by the pharmaceutical industry in drug development, since it can make the process of discovery and documentation of pharmacological and toxicological profile more effective [12]
Taken together there are numerous examples where pharmacometabolomics has contributed to better understanding of drug treatment and risk for adverse effect

Summary

Introduction

TDM today Therapeutic drug monitoring (TDM) is a concept for individualized drug dosing that was developed into clinical routine as a consequence of research findings on variable drug effects and analytical technology developments made in the 1950th and onwards, and founded the clinical pharmacology discipline [1,2]. Analytical method demands in TDM are set by the requirements of accuracy, cost-effectiveness, rapid reporting and robustness in a routine laboratory environment. The pharmacometabolomic approach comprises using both NMR and mass spectrometry methods to collect non-targeted analytical data sets and apply statistical methods to make discoveries.

Results

Conclusion