μPESI-MS/MS System for Screening and Quantitating Drugs in Plasma Samples

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Pharmacology

Background:

• Quantitative analysis of drugs in biological matrices is crucial for therapeutic drug monitoring and pharmacokinetic studies.
• Existing methods may require extensive sample preparation or specialized equipment.
• A novel microprobe electrospray ionization (μPESI) source coupled with tandem mass spectrometry (MS/MS) was previously developed.

Purpose of the Study:

• To validate the μPESI-MS/MS method for the quantitative analysis of drugs in plasma samples.
• To investigate the relationship between drug physicochemical properties and the quantitative performance of the μPESI-MS/MS method.

Main Methods:

• Development and validation of μPESI-MS/MS methods for 5 representative drugs.
• Assessment of linearity, accuracy, and precision against European Medicines Agency (EMA) guidelines.
• Analysis of 75 drugs in plasma samples, with a focus on quantitative performance and physicochemical properties (log P, pKa, charge).

Main Results:

• μPESI-MS/MS methods met EMA requirements for linearity, accuracy, and precision for the tested drugs.
• 48 out of 75 drugs were successfully quantified in plasma samples.
• Logistic regression indicated that higher log P values and physiological charge positively correlated with better quantitative performance.

Conclusions:

• The μPESI-MS/MS system is a validated and practical method for rapid drug quantification in plasma.
• Drug physicochemical properties, specifically lipophilicity and charge, influence the quantitative performance of the μPESI-MS/MS method.
• This technique offers a promising approach for high-throughput drug analysis in clinical and research settings.