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

Background: Aminoglycosides are last-resort antibiotics for bacterial infections due to concerns of nephrotoxicity. A robust method is needed to correlate the magnitude of drug accumulation in the kidneys and the onset of nephrotoxicity. Materials & methods: A LC-MS/MS assay was developed, circumventing common limitations associated with conventional assays. To demonstrate its applicability, renal cellular uptake and rat pharmacokinetic studies were performed with amikacin. Results: To improve elution, the mobile phases were optimized with 60 mM ammonium hydroxide (pH = 11.2). An extended quantifiable range was achieved with different ionization modes. Kidney cells incubated with escalating amikacin concentrations showed increased uptake. Single-dose pharmacokinetics of amikacin were reasonably characterized. Conclusion: This assay will facilitate future studies on improving amikacin-associated nephrotoxicity.