Quantification of amikacin, gentamicin, and tobramycin in capillary plasma microsamples by LC-MS/MS

Area of Science:

• Pharmacokinetics and Therapeutic Drug Monitoring
• Analytical Chemistry and Mass Spectrometry
• Clinical Diagnostics and Patient Care

Background:

• Aminoglycoside antibiotics (amikacin, gentamicin, tobramycin) require plasma concentration monitoring for effective treatment.
• Minimizing patient discomfort necessitates exploring less invasive blood collection methods.
• Capillary blood microsampling offers a promising alternative to conventional venous blood collection.

Purpose of the Study:

• To develop and validate an LC-MS/MS method for quantifying amikacin, gentamicin, and tobramycin in capillary plasma microsamples.
• To compare aminoglycoside concentrations in capillary plasma microsamples with those in conventional venous plasma.
• To assess the clinical applicability of capillary microsampling for therapeutic drug monitoring of aminoglycosides.

Main Methods:

• Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.
• Collection of capillary plasma microsamples using TASSO+® devices or heparinized glass capillaries.
• Validation according to ICH guidelines, including linearity, accuracy, precision, and matrix effects.

Main Results:

• The LC-MS/MS method demonstrated excellent linearity, high extraction efficiency (>85%), and acceptable accuracy and precision for all analytes.
• Analysis of 23 paired venous and capillary samples showed strong agreement (r > 0.97) between the two collection methods for amikacin and gentamicin.
• Matrix effects were within acceptable ranges (5.5% to 20.5%).

Conclusions:

• Capillary microsampling is a viable and clinically applicable alternative for therapeutic drug monitoring of aminoglycosides.
• This method reduces patient discomfort associated with traditional venous blood draws.
• The validated LC-MS/MS assay provides reliable quantification of aminoglycosides in small capillary plasma volumes.