Liquid Chromatography-Tandem Mass Spectrometry to Monitor Unbound and Total Ceftriaxone in Serum of Critically Ill Patients

(E-pub Ahead of Print)

Author(s): Sjoerd Meenks*, Jos le Noble, Norbert Foudraine, Frank de Vries, Paddy Janssen

Journal Name: Current Reviews in Clinical and Experimental Pharmacology
(Formerly Current Clinical Pharmacology)


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Abstract:

Background: Ceftriaxone is recommended for empiric antimicrobial therapy in patients with sepsis. Therapeutic drug monitoring (TDM) guided dose optimisation could elucidate pharmacokinetic variabilities, improving treatment efficacy. However, detailed data on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for unbound ceftriaxone quantification in serum are scarce.

Objective: The authors aimed to develop a reliable UPLC-MS/MS method for serum ceftriaxone quantification and exhibit its application potential in routine hospital settings.

Methods: In this observational, single centre study, UPLC-MS/MS method validation included specificity, carry-over, linearity, repeatability, intermediate precision, accuracy, the limit of quantification, and plasma protein binding. Unbound and total ceftriaxone were quantified in the serum of 5 critically ill patients. Pharmacokinetic/pharmacodynamic (PK/PD) target attainment calculations were performed for both unbound and total ceftriaxone. The PK/PD target for unbound ceftriaxone in serum was set at 4 times the non-species related minimum inhibitory concentration breakpoint of 1 mg/L for at least 60% of the dosing interval.

Results: The UPLC-MS/MS method revealed acceptable limits for clinical samples, with coefficients of variation < 15.0% for concentrations between 0.2 – 400.0 mg/L. Ceftriaxone eluted at 1.94 min and ceftazidime, as internal standard, eluted at 1.42 min. Patients demonstrated a median unbound ceftriaxone fraction of 29.1% (IQR: 15.2 – 52.2). Day 1 of ceftriaxone treatment presented a median PK/PD target attainment of 100.0% (IQR: 81.1 – 100.0) for unbound ceftriaxone in serum, while for calculations based on total concentrations, this figure was 23.9% (IQR: 10.5 – 80.6).

Conclusion: The described UPLC-MS/MS method enables reliable and rapid ceftriaxone quantification in the serum of critically ill patients. Method feasibility was exhibited for TDM purposes in routine clinical practice.

Keywords: Ceftriaxone, unbound, monitoring, mass spectrometry, critically ill.

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1574884715666201228115150
Price: $95

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