Simultaneous Retrodialysis by Calibrator for Rapid In Vivo Recovery Determination in Target Site Microdialysis

Concentrations in the interstitial tissue space are of clinical interest for many antibiotics and can be directly measured by microdialysis. Quantitative microdialysis strongly depends on reliable recovery estimates obtained from a suitable calibrator. Cefazolin (CFZ) is frequently used as a prophylactic antibiotic to prevent surgical site infections. This study aimed to develop a reliable and rapid calibration technique for CFZ microdialysis using cefuroxime (CFR) as a calibrator, which is applied simultaneously in the opposite direction via retrodialysis. Liquid chromatography-tandem mass spectrometry method was used for the measurement of both CFZ and CFR in microdialysate. Results from in vitro microdialysis experiments confirmed that CFR does not interfere with physicochemical properties of CFZ, and the loss of CFR is proportional to the gain of CFZ in microdialysis studies. Therefore, the validated bioanalytical assay is suitable to be applied in clinical microdialysis study of CFZ where microdialysis probes are simultaneously calibrated by retrodialysis of CFR. This approach shortens the overall sampling time of in vivo microdialysis studies significantly since calibration and sampling can be performed simultaneously and not in sequence as usually done. It also eliminates the necessary washout period if probe calibration is carried out before the actual sampling time.