Evaluation Study of Dried Blood Spot Technology for Guiding Precision Dosing of Meropenem in Critically Ill Patients with Severe Infection

OBJECTIVE To develop an assay for determining meropenem blood concentrations using dried blood spot(DBS) technology and to evaluate its application value in guiding precision dosing for critically ill patients with severe infection.

METHODS Meropenem concentrations in DBS samples were quantified using HPLC. The sample pretreatment procedures and chromatographic conditions were optimized, followed by a full method validation including specificity, linearity, accuracy, precision, extraction recovery, matrix effects, and stability. The agreement between meropenem concentrations measured in DBS and paired conventional venous plasma samples was assessed using Bland-Altman and Passing-Bablok regression analyses. Clinical utility of testing samples from critically ill patients with severe infection was verified.

RESULTS The established DBS-HPLC demonstrated excellent linearity over the concentration range of 1−100 μg·mL⁻¹(R²=0.9982), with a lower limit of quantification of 1 μg·mL⁻¹. The specificity, accuracy, precision, extraction recovery, matrix effects, and stability all met the acceptance criteria for bioanalytical method validation. DBS technology maintained the stability of meropenem for 72 h under ambient temperature, 4 ℃, and −20 ℃ conditions, with superior stability at ambient temperature compared to plasma samples. Meropenem blood concentration results obtained from DBS sampling demonstrated good consistency with those from traditional venous plasma sampling. Clinical monitoring showed that 98% (49/50) of patients achieved the target trough concentration of meropenem based on DBS analysis verified by conventional venous plasma testing.

CONCLUSION DBS-HPLC enables rapid and minimally-invasive monitoring of meropenem blood concentration, offering reliable support for personalized antimicrobial therapy in critically ill patients with severe infection.