LC-MS/MS analysis of five antibiotics in dried blood spots for therapeutic drug monitoring of ICU patients

In the intensive care unit (ICU), optimizing antimicrobial therapy through Therapeutic Drug Monitoring (TDM) can significantly improve patient outcomes. We developed and validated a DBS method for the simultaneous quantification of five antibiotics commonly used in ICUs, namely imipenem, meropenem, tigecycline, teicoplanin, and vancomycin. Dried blood spots (DBS) were prepared by spotting 30 μL of blood onto Whatman 903® cards and analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The DBS concentrations measured were compared with serum concentrations analyzed using standard laboratory methods. The paired DBS and serum samples were obtained from ICU. Deming regression and Bland-Altman difference plot were used to assess the consistency between the two methods. The DBS method was validated including selectivity, carryover, precision (0.078-16.70 %), accuracy (85.19-117.17 %), matrix effect, recovery (46.51 %-114.15 %), linearity, and dilution integrity. DBS samples stability at -80 °C for at least 30 days. DBS and serum concentrations of two antibiotics were compared, and statistical analysis confirmed good correlation (r > 0.97) between them. This study provides a new approach to TDM, suggesting that DBS may replace or complement traditional analytical sampling techniques. It has been validated for guiding individualized antimicrobial therapy in ICU patients.