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

Abstract

Aminoglycoside antibiotics, including amikacin (AMI), gentamicin (GEN), and tobramycin (TOB), are widely used to treat infections, necessitating plasma concentration monitoring to achieve therapeutic targets and optimize patient treatment. To minimize patient discomfort, less invasive blood collection methods are desirable. Capillary blood microsampling provides an alternative to conventional venous collection, enabling the extraction of small plasma volumes via distal puncture or self-lancing devices. This study developed and validated an LC-MS/MS method for quantifying AMI, GEN, and TOB in plasma microsamples, comparing concentrations obtained from venous and capillary plasma. Capillary samples were collected using the TASSO⁺® device or heparinized glass capillaries. The method was validated according to ICH guidelines, demonstrating linearity of 0.5–50 mg/L for GEN and 1.0–100 mg/L for AMI and TOB, with extraction efficiencies exceeding 85 % for all analytes. Accuracy ranged from 94.9 % to 108.1 %, with precision between 1.04 % and 5.62 %, and matrix effects of 5.5 % to 20.5 %. A total of 23 paired venous and capillary plasma samples were analyzed, with Passing-Bablok regression revealing strong agreement between venous and capillary plasma concentrations for AMI (r = 0.980, P < 0.0001) and GEN (r = 0.979, P < 0.0001). These findings suggest that capillary microsampling is a viable and clinically applicable alternative for therapeutic drug monitoring of aminoglycosides.