Therapeutic drug monitoring of cefepime with micellar electrokinetic capillary chromatography: Assay improvement, quality assurance, and impact on patient drug levels

Abstract

The improvement and performance of a micellar electrokinetic capillary chromatography assay for cefepime in human serum and plasma with a 50 μm id fused-silica capillary elongated from 40 to 60 cm is reported. Sample preparation with dodecylsulfate protein precipitation at pH 4.5, the pH 9.1 separation medium, and the applied voltage were as reported previously [16]. The change resulted in a significant lower current, higher resolution, and increased detection time intervals. The performance of the assay with multilevel internal calibration was assessed with calibration and control samples. Quality assurance data of a 2-year period assessed under the new conditions demonstrated the robustness of the assay. In serum samples of patients who received both cefepime and sulfamethoxazole, cefepime could not be detected due to the inseparability of the two compounds. The presence of an interference can be recognized by an increased peak width (width > 0.2 min), the appearance of a shoulder or an unresolved double peak. The patient data gathered during a 3-year period reveal that introduction of therapeutic drug monitoring led to a 50% reduction of the median drug level. The data suggest that therapeutic drug monitoring can help to minimize the risk of major adverse reactions and to increase drug safety on an individual basis.

Monitoring of cefepime in urine by micellar electrokinetic capillary chromatography with ultraviolet detection and liquid chromatography coupled to mass spectrometry

“…Intra‐ and interday drug level repeatability was found to be ≤5.9 and ≤8.6%, respectively. These data compare well with those reported for the MEKC assay to monitor cefepime levels in serum und plasma .…”

“…The cefepime results of urine and serum analyses are presented in Table . Cefepime serum levels were in the expected range, according to our previous experience with TDM . Cefepime urine levels showed a broad range of results, depending on renal function, dosing and excreted urinary volume.…”

“…In the used assay format, internal standard and cefepime were detected around 8.8 and 10.7 min, respectively (Figure ), and the current was about 24 μA, values that are comparable to those under the assay conditions for serum and plasma . Electropherograms obtained with a blank urine fortified with the internal standard and a calibrator urine comprising 60 μg/mL cefepime and the internal standard are presented in panels A and B, respectively, of Figure .…”

Monitoring of cefepime in human serum and plasma by micellar electrokinetic capillary chromatography: Improvement of sample preparation and validation by liquid chromatography coupled to mass spectrometry

“…Data gathered thus far suggest that TDM can help to minimize the risk of major adverse reactions and to increase drug safety on an individual basis . Analytical methods for monitoring cefepime in biosamples include bioassays , HPLC with UV detection , LC–MS , and MEKC . They should be capable of accurately monitoring cefepime levels in the range of 1 to 50 μg/mL .…”

“…MEKC electropherograms obtained for a patient sample comprising sulfomethoxazole by analysis (A) with sample matrix of the routine method , (B) of the aqueous phase after extraction with dichloromethane from the same sample matrix, (C) with the new sample matrix, (D) of the aqueous phase after extraction with dichloromethane from the new sample matrix, and (E) of sample D spiked with cefepime. The inserts in panels B and D depict corresponding electropherograms obtained for the analysis of the organic phases.…”