A high performance liquid chromatography-tandem mass spectrometry assay for therapeutic drug monitoring of 10 drug compounds commonly used for antimicrobial therapy in plasma and serum of critically ill patients: Method optimization, validation, cross-validation and clinical application.
Clin Chim Acta
; 559: 119690, 2024 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-38677452
ABSTRACT
BACKGROUND AND AIMS:
Intensive care antibiotic treatment faces challenges due to substantial pharmacokinetic differences in critically ill patients. Individualized antibiotic dosing guided by therapeutic drug monitoring (TDM) is considered to minimize the risk of treatment failure and toxicity. This study aimed to develop a valid method for simultaneous LC-MS/MS quantification of 10 drugs frequently used in intensive care antibiotic therapy for which TDM-guided dosing is recommended piperacillin, meropenem, flucloxacillin, cefuroxime, vancomycin, colistin A and B, linezolid, ciprofloxacin and tazobactam. METHODS ANDRESULTS:
Thorough optimization of sample preparation and chromatography resulted in a fast and simple method based on protein precipitation of 50 µL plasma or serum and gradient elution using an Acquity UPLC HSS-T3 column. Electrospray ionization-triple quadrupole mass spectrometry in dynamic multiple reaction monitoring was used for quantification, covering the therapeutic range of each drug compound. Validation following EMA and FDA recommendations, including inter-platform validation and inter-laboratory comparison, demonstrated high accuracy, precision and robustness of the new method. The assay was successfully used to monitor plasma antibiotic levels of critically ill patients (n = 35).CONCLUSION:
The established multiplex method covers major drug classes with documented dosing challenges, provides a reliable basis for the implementation of high-throughput TDM, and its application confirmed the clinical impact of TDM in a real-world setting.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Monitoreo de Drogas
/
Enfermedad Crítica
/
Espectrometría de Masas en Tándem
Límite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Clin Chim Acta
Año:
2024
Tipo del documento:
Article
País de afiliación:
Alemania