Feasibility verification of fingerstick capillary microsampling replacing venipuncture for therapeutic drug monitoring of 12 antibiotics using a rapid LC-MS/MS assay

Therapeutic drug monitoring (TDM) is essential for optimizing antimicrobial therapy and curbing resistance, yet conventional venipuncture limits its widespread application due to invasiveness and operational complexity. This study aimed to establish a rapid LC-MS/MS method for simultaneous quantification of 12 antimicrobial agents and to evaluate the feasibility of using fingertip capillary serum as an alternative to venous serum for TDM. A liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous quantification of vancomycin, linezolid, voriconazole, sulfamethoxazole, trimethoprim, piperacillin, cefoperazone, ceftazidime, ceftobiprole, meropenem, imipenem, and cilastatin in human serum. The method was applied to analyze 379 paired clinical samples (fingertip serum versus venous serum), and agreement between the two sampling approaches was assessed using Deming regression and Bland Altman analysis. The method required only 10 μL of serum and a total run time of 4 min. Deming regression slopes ranged from 0.910 to 1.017. Bland Altman analysis showed that 100.0% of the data points fell within ±20.0% limits of agreement for all antibiotics except vancomycin (96.7%) and cilastatin (97.5%). This study provides large scale clinical evidence demonstrating high concordance between fingertip serum and venous serum concentrations for 12 antimicrobial agents. By directly obtaining serum, this approach fundamentally avoids the hematocrit effect and matrix conversion issues inherent in whole blood microsampling, offering a minimally invasive TDM strategy fully aligned with the gold standard matrix. This strategy is particularly suitable for special populations such as children, the elderly, and critically ill patients.