Development of Simultaneous Drug Concentration Measurement Method Using an Automated Pretreatment Liquid Chromatography/Tandem Mass Spectrometry System for Therapeutic Drug Monitoring

Abstract

Therapeutic drug monitoring (TDM) is a personalized treatment approach that involves optimizing drug dosages based on patient-specific factors, such as drug plasma concentrations, therapeutic efficacy, or adverse reactions. The plasma concentration of drugs is determined using liquid chromatography/tandem mass spectrometry (LC-MS/MS) or various immunoassays. Compared with immunoassays, LC-MS/MS requires more pretreatment time as the number of samples increases. Recently, fully automated pretreatment LC-MS/MS systems have been developed to automatically perform whole-sample pretreatment for LC-MS/MS analysis. In this study, we developed a method for simultaneous concentration determination of five analytes (clozapine, mycophenolic acid, sunitinib, N-desethylsunitinib, and voriconazole) using LC-MS/MS for clinical TDM using a fully automated LC-MS/MS pretreatment system. In the developed method, the intra- and inter-assay relative error (RE) values ranged between −14.8% and 11.3%; the intra- and inter-assay coefficient of variation (CV) values were <8.8% and <10.5%, respectively. The analytes showed good stability, with RE values ranging between −13.6% and 10.9% and CV values <8.9%. Furthermore, the plasma concentrations in clinical samples using this method and the conventional manual pretreatment method showed similar results. Therefore, the method developed in this study could be considered a useful pretreatment method for routine TDM in patients.

Keywords

• automated sample preparation
• therapeutic drug monitoring
• LC-MS/MS
• plasma concentration
• simultaneous measurement method of drug efficacy