Validation and Application of an HPLC-UV Method for Routine Therapeutic Drug Monitoring of Cefiderocol

Cefiderocol is a new siderophore cephalosporin approved for the treatment of multidrug resistant bacteria including activity against carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa. As cephalosporins are known for their high pharmacokinetic variability in critically ill patients, cefiderocol therapeutic drug monitoring might become a valuable tool. Therefore, we aimed to develop and validate a simple, rapid, cost-effective high performance liquid chromatography (HPLC) method for the quantification of cefiderocol in serum. Samples were treated for protein precipitation followed by chromatographic separation on a reverse phase column (HPLC C-18) with gradient elution of the mobile phase. Cefiderocol was detected via UV absorption and quantification was performed with the internal standard (metronidazole) method. The calibration range showed linearity from 4 to 160 mg/L. The intra and interday precision was less than 10% with a recovery rate of 81%. The method was successfully used for the analysis of subsequent serum samples of critically ill patients and showed good performance in monitoring serum levels and optimizing antibiotic therapy.

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An UHPLC-UV Method for Determination of Vancomycin in human serum

Current Pharmaceutical Analysis ◽

10.2174/1573412916999200519140258 ◽

2020 ◽

Vol 16 ◽

Author(s):

Fang Fang ◽

Ning Li ◽

Chunli Xu ◽

Rong Tan ◽

Jihong Yang ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Human Serum ◽

Drug Monitoring ◽

Internal Standard ◽

Sample Pretreatment ◽

Gradient Elution ◽

Therapeutic Drug ◽

Serum Samples ◽

Column Temperature ◽

Limit Of Quantitation

Objective: To develop a rapid ultra-performance liquid chromatographic (UHPLC)-UV method for vancomycin determination in human serum for therapeutic drug monitoring (TDM). Methods: Human serum samples were precipitated with 10% perchloric acid, and the supernatant after centrifugation was analyzed on an ACQUITY UHPLC BEH C18 column (2.1 × 50mm, 1.7 μm) via gradient elution with a flow rate at 0.3 mL/min. The mobile phase consisted of acetonitrile and 0.005M KH2PO4 buffer (containing 0.1% triethylamine, pH 3.4). The detection wavelength was set at 210 nm, and the column temperature was set at 40. The total runtime was 6.0 min per analysis. Results: After comprehensive validation, the method was applied to determine the concentration of vancomycin in human serum. The chromatographic peaks of vancomycin and internal standard were not interfered by endogenous matrixes. The retention time (RT) of vancomycin was 1.91 min, while the internal standard was 1.58 min. The good linearity range of vancomycin concentration was 2.5-120 μg/mL (R2>0.999). The lower limit of quantitation (LLOQ) was 2.5 μg/mL. The precision at three quality control (QC) levels (including LLOQ) was restricted within 85-115%. The extraction recovery rate of QC samples (4.0, 20.0, 60.0 μg/mL) were 101.16%、97.70%、94.90%, respectively. Inter- and intra-day precision was less than 8% (RSD). Stability tests under different storage conditions were satisfactory. In patients, the concentration of vancomycin ranged from 7.30 to 89.12 μg/mL determined by the fully validated method. Conclusion: The simple, rapid sample pretreatment procedures and short analysis time made this UHPLC-UV method suitable for therapeutic drug monitoring (TDM) of vancomycin.

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Therapeutic Drug Monitoring of Fluconazole in Critically Ill Patients

Case Medical Research ◽

10.31525/ct1-nct04252027 ◽

2020 ◽

Author(s):

Keyword(s):

Therapeutic Drug Monitoring ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Therapeutic Drug

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How do we use therapeutic drug monitoring to improve outcomes from severe infections in critically ill patients?

BMC Infectious Diseases ◽

10.1186/1471-2334-14-288 ◽

2014 ◽

Vol 14 (1) ◽

Cited By ~ 51

Author(s):

Gloria Wong ◽

Fekade Bruck Sime ◽

Jeffrey Lipman ◽

Jason A Roberts

Keyword(s):

Therapeutic Drug Monitoring ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Therapeutic Drug ◽

Severe Infections

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Barriers and facilitators in the clinical implementation of beta-lactam therapeutic drug monitoring in critically ill patients

Therapeutic Drug Monitoring ◽

10.1097/ftd.0000000000000937 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Alan Abdulla ◽

Puck van den Broek ◽

Tim M.J. Ewoldt ◽

Anouk E. Muller ◽

Henrik Endeman ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Barriers And Facilitators ◽

Therapeutic Drug ◽

Clinical Implementation ◽

Beta Lactam

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Therapeutic Drug Monitoring of Protein Unbound Ciprofloxacin Concentrations to avoid inadequate Treatment of severe Bacterial Infections in Critically ill Patients

Journal of Applied Bioanalysis ◽

10.17145/jab.18.021 ◽

2018 ◽

Vol 4 (5) ◽

pp. 166-174

Author(s):

Nora J mabelis ◽

Kimberly N. Shudofsky ◽

Joost J. van Raaij ◽

Sjoerd D. Meenks ◽

Thomas Havenith ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Bacterial Infections ◽

Therapeutic Drug

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Personalized Antibiotic Therapy for the Critically Ill: Implementation Strategies and Effects on Clinical Outcome of Piperacillin Therapeutic Drug Monitoring—A Descriptive Retrospective Analysis

Antibiotics ◽

10.3390/antibiotics10121452 ◽

2021 ◽

Vol 10 (12) ◽

pp. 1452

Author(s):

Schrader Nikolas ◽

Riese Thorsten ◽

Kurlbaum Max ◽

Meybohm Patrick ◽

Kredel Markus ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Antibiotic Therapy ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Implementation Strategy ◽

Care Staff ◽

Therapeutic Drug ◽

Health Care Staff ◽

Standard Operating

Therapeutic drug monitoring (TDM) is increasingly relevant for an individualized antibiotic therapy and subsequently a necessary tool to reduce multidrug-resistant pathogens, especially in light of diminishing antimicrobial capabilities. Critical illness is associated with profound pharmacokinetic and pharmacodynamic alterations, which challenge dose finding and the application of particularly hydrophilic drugs such as β-lactam antibiotics. Methods: Implementation strategy, potential benefit, and practicability of the developed standard operating procedures were retrospectively analyzed from January to December 2020. Furthermore, the efficacy of the proposed dosing target of piperacillin in critically ill patients was evaluated. Results: In total, 160 patients received piperacillin/tazobactam therapy and were subsequently included in the study. Of them, 114 patients received piperacillin/tazobactam by continuous infusion and had at least one measurement of piperacillin serum level according to the standard operating procedure. In total, 271 measurements were performed with an average level of 79.0 ± 46.0 mg/L. Seventy-one piperacillin levels exceeded 100 mg/L and six levels were lower than 22.5 mg/L. The high-level and the low-level group differed significantly in infection laboratory parameters (CRP (mg/dL) 20.18 ± 11.71 vs. 5.75 ± 5.33) and renal function [glomerular filtration rate (mL/min/1.75 m2) 40.85 ± 26.74 vs. 120.50 ± 70.48]. Conclusions: Piperacillin levels are unpredictable in critically ill patients. TDM during piperacillin/tazobactam therapy is highly recommended for all patients. Although our implementation strategy was effective, further strategies implemented into the daily clinical workflow might support the health care staff and increase the clinicians’ alertness.

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