A robust LC-MS/MS method for amikacin: application to cellular uptake and pharmacokinetic studies

Area of Science:

• Pharmacology
• Analytical Chemistry
• Toxicology

Background:

• Aminoglycosides are critical last-resort antibiotics.
• Nephrotoxicity is a significant concern with aminoglycoside use.
• A reliable method to link kidney drug accumulation and toxicity is needed.

Purpose of the Study:

• Develop and validate a robust LC-MS/MS assay for quantifying aminoglycosides in renal tissue.
• Establish a correlation between amikacin concentration in kidney cells and pharmacokinetic parameters.
• Facilitate future research on mitigating amikacin-induced nephrotoxicity.

Main Methods:

• Developed a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay.
• Optimized mobile phase composition (60 mM ammonium hydroxide, pH 11.2) for improved elution.
• Conducted renal cellular uptake and rat pharmacokinetic studies using amikacin.

Main Results:

• The LC-MS/MS assay demonstrated an extended quantifiable range and improved ionization efficiency.
• Increased amikacin uptake was observed in kidney cells with escalating drug concentrations.
• Single-dose pharmacokinetic profiles of amikacin in rats were successfully characterized.

Conclusions:

• The developed LC-MS/MS assay provides a reliable tool for studying aminoglycoside nephrotoxicity.
• This assay will advance the understanding of amikacin accumulation in the kidneys.
• Future studies can utilize this method to develop strategies for reducing amikacin-associated kidney damage.