Development of Simultaneous Drug Concentration Measurement Method Using an Automated Pretreatment Liquid...

Area of Science:

• Clinical Chemistry
• Analytical Chemistry
• Pharmacology

Background:

• Therapeutic drug monitoring (TDM) personalizes medication by adjusting doses based on patient-specific drug levels, efficacy, and adverse reactions.
• Liquid chromatography/tandem mass spectrometry (LC-MS/MS) is a key technique for determining drug plasma concentrations, but manual pretreatment can be time-consuming.
• Fully automated LC-MS/MS systems offer a solution to reduce sample pretreatment time and improve efficiency in clinical laboratories.

Purpose of the Study:

• To develop and validate a simultaneous LC-MS/MS method for quantifying five analytes (clozapine, mycophenolic acid, sunitinib, N-desethylsunitinib, and voriconazole) in human plasma.
• To evaluate the performance of a fully automated LC-MS/MS pretreatment system for routine clinical TDM.
• To compare the results obtained from the automated method with conventional manual pretreatment techniques.

Main Methods:

• Development of a simultaneous LC-MS/MS assay for five target drugs.
• Utilization of a fully automated sample pretreatment system for LC-MS/MS analysis.
• Validation of the method by assessing intra- and inter-assay precision, accuracy, and analyte stability.

Main Results:

• The developed automated LC-MS/MS method demonstrated good accuracy and precision, with intra- and inter-assay relative error (RE) values between -14.8% and 11.3%, and coefficient of variation (CV) <8.8% and <10.5%, respectively.
• Analyte stability was confirmed, with RE values ranging from -13.6% to 10.9% and CV values <8.9%.
• Plasma concentrations measured using the automated method closely correlated with those obtained via conventional manual pretreatment.

Conclusions:

• A fully automated LC-MS/MS pretreatment method enables efficient and reliable simultaneous determination of multiple drug concentrations for clinical TDM.
• This automated approach provides results comparable to manual methods, making it suitable for routine TDM applications.
• The developed method supports personalized medicine by facilitating timely and accurate drug dosage optimization in patient care.