Fundamental Study of Behaviors of In-Source Collision Induced Dissociation and Shifting the Linear Range of Calibration Curves of Various Drugs and the Metabolites Used for Therapeutic Drug Monitoring

Abstract

Therapeutic drug monitoring (TDM) is a clinical practice that designs personalized medication for patients with blood concentrations of the drug. TDM approach is used for many drugs, including immunosuppressant, antifungal, antiarrhythmic, and anti-cancer drugs. Combination therapies are often adopted in TDM. Liquid chromatography tandem mass spectrometry (LC-MS/MS) is a useful analytical method in such cases. However, the development of a simultaneous LC-MS/MS analytical method is difficult owing to the differences in MS sensitivity and the therapeutic range of each drug. In order to avoid saturation of the detector, in-source collision induced dissociation (CID) was used to reduce the ion inlet. In this study, we investigated the in-source CID behavior of 13 compounds of drugs and metabolites in TDM practice. As a result, all compounds provided a sharp reduction of ion inlet over the threshold ion guide voltage. In addition, a shift to the higher concentration of the calibration range was observed according to such changes. The intensity and linearity data in this study that all 13 drugs could be analyzed under in-source CID conditions simultaneously. These results might be useful for TDM of combination therapy in clinical practice.