Simultaneous Determination of Multiple Acid-Suppressing Drugs by UPLC-MS/MS Method and Application for...

Area of Science:

• Analytical Chemistry
• Pharmacology
• Clinical Diagnostics

Background:

• Proton pump inhibitors (PPIs) and potassium competitive acid blockers (P-CABs) are essential for managing acid-related diseases (ARDs).
• Accurate quantification of plasma drug concentrations is critical for effective clinical pharmacokinetic assessments and therapeutic drug monitoring.

Purpose of the Study:

• To develop and validate a universal and efficient ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay.
• To simultaneously determine the plasma concentrations of five PPIs (esomeprazole, rabeprazole, ilaprazole, lansoprazole, pantoprazole) and one P-CAB (vonoprazan).

Main Methods:

• Analyte extraction from human plasma using protein precipitation and a single dilution step.
• Detection via positive electrospray ionization on a triple quadrupole tandem mass spectrometer.
• Chromatographic separation on an ACQUITY UPLC BEH C18 column with gradient elution using acetonitrile and ammonium formate/ammonium hydroxide mobile phases.

Main Results:

• The assay demonstrated excellent linearity over specified ranges (0.2–200 ng/mL for PPIs, 0.5–500 ng/mL for P-CAB).
• High precision (1.1%–14.6%) and accuracy (0.0%–14.7%) were achieved, with consistent extraction recoveries (88.1%–96.7%) and no significant matrix effects.
• Analyte stability was confirmed under various conditions, with all metrics within acceptable limits (±15%).

Conclusions:

• The developed UPLC-MS/MS method is efficient and reliable for the simultaneous determination of six key acid-suppressing medications.
• This assay serves as a valuable tool for pharmacokinetic studies and therapeutic drug monitoring in clinical research settings.