Abstract: Objective To establish a fully automated 2-dimensional liquid chromatography with ultraviolet detection (2D-LC/UV) method for determining the concentration of meropenem in plasma from critically ill patients and to apply it in clinical practice. Methods A 2D-LC/UV system was adopted. Plasma samples were processed with a protein precipitant. Online solid-phase extraction was performed on a one-dimensional column-Aston SNCB (4.6 mm×50 mm, 5 μm)-for preliminary enrichment and separation of meropenem before the target analyte was transferred to a two-dimensional column-Aston SNBR (4.6 mm×200 mm, 5 μm)- for further separation and detection. The mobile phases for the one-dimensional and two-dimensional columns were meropenem-1D and BPI-1 alkaline, respectively, at a flow rate of 1.0 mL·min^-1. The column temperature was 40℃, and the detection wavelength was 310 nm. The external standard method was used for quantification. Results Meropenem showed good linearity at concentrations ranging from 1.837 5 to 147 μg·mL^-1, with a correlation coefficient (R²) of 0.999 98. The relative recoveries for the low-, medium-, and high-concentration (1.5、20.0、80.0 μg·mL^-1) quality controls (QCs) exceeded 95%, and both intra- and inter-day precision (RSD%) was below 5%. Conclusion This method proves to be capable of accurate and efficient automated analysis while streamlining the pretreatment process and reducing costs. Furthermore, it is sensitive enough for high-throughput monitoring of steady-state trough concentrations of meropenem.

Key words: Meropenem, Blood Drug Concentration, Plasma, 2-Dimensional Liquid Chromatography with Ultraviolet Detection(2D-LC/UV), Monitoring