Development of a UHPLC-UV/Vis Method for Simultaneously Determining Six Beta-Lactam Antibiotics in Plasma: A Tool for the Clinical Implementation of Therapeutic Monitoring of Beta-Lactams
<b>Background/Introduction:</b> Beta-lactam antibiotics are among the most frequently prescribed drugs in clinical practice, yet their therapeutic drug monitoring remains underutilized despite high interindividual pharmacokinetic variability, especially in critically ill patients. <b&...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/14/6/613 |
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| Summary: | <b>Background/Introduction:</b> Beta-lactam antibiotics are among the most frequently prescribed drugs in clinical practice, yet their therapeutic drug monitoring remains underutilized despite high interindividual pharmacokinetic variability, especially in critically ill patients. <b>Methods:</b> To address this, we developed and validated an ultra-high-performance liquid chromatography (UHPLC-UV/Vis) method for the simultaneous quantification of six beta-lactams (cefepime, ceftolozane, ceftazidime, meropenem, ampicillin, and ertapenem) in plasma. <b>Results:</b> This method uses a single gradient mobile phase and a photodiode array detector, ensuring accurate separation, minimal interference, and robust analyte identification. Validation followed EMA bioanalytical guidelines, demonstrating selectivity, precision, accuracy, and linearity within clinically relevant ranges (1.0–50.0 mg/L). Stability tests showed that the analytes were stable in plasma for up to seven days at 4 °C and one month at −20 °C. Pilot clinical implementation in 35 patients revealed significant interindividual variability, supporting the need for routine beta-lactam monitoring. Approximately 26% of trough concentrations were below the minimal inhibitory concentration, while others exceeded thresholds associated with potential toxicity. <b>Discussion</b>: This study represents the first UHPLC-UV/Vis method for the simultaneous determination of these six beta-lactams, overcoming limitations of prior methods that required different mobile phases or excluded clinically relevant antibiotics. The method is universally applicable and easily transferable to routine clinical practice. <b>Conclusions:</b> These findings underline the importance of beta-lactam monitoring in optimizing treatment outcomes and combating antibiotic resistance in vulnerable populations. Further studies to assess free drug concentrations are warranted to enhance clinical applicability. |
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| ISSN: | 2079-6382 |