Determination of free clindamycin, flucloxacillin or tedizolid in plasma: Pay attention to physiological conditions when using ultrafiltration

Abstract

Pharmacokinetic/pharmacodynamic indices of anti‐infective drugs should be referenced to free drug concentrations. In the present study, clindamycin, flucloxacillin and tedizolid have been determined in human plasma by HPLC–UV. The drugs were separated isocratically within 3–6 min on a C18 column using mixtures of phosphate buffer–acetonitrile of pH 7.1–7.2. Sample treatment for the determination of total drug concentrations in plasma included extraction/back‐extraction (clindamycin) or protein precipitation (flucloxacillin, tedizolid). The free drug concentrations were determined after ultrafiltration. An ultrafiltration device with a membrane consisting of regenerated cellulose proved to be suitable for all drugs. Maintaining a physiological pH was crucial for clindamycin, whereas maintaining body temperature was essential for tedizolid. The methods were applied to the analysis of total and free drug concentrations in clinical samples and were sufficiently sensitive for pharmacokinetic studies and therapeutic drug monitoring.

A meta-analysis of protein binding of flucloxacillin in healthy volunteers and hospitalized patients

“…For highly protein bound drugs, ultrafiltration performed at ambient temperature might lead to an underestimation of the unbound fraction (29)(30)(31). Ultrafiltration performed at physiological temperature (37°C) is likely to give a better representation of protein binding in vivo and is, therefore, recommended.…”

Measurement of Free Plasma Concentrations of Beta-Lactam Antibiotics: An Applicability Study in Intensive Care Unit Patients

“…The drugs were analyzed by high-performance liquid chromatography with ultraviolet detection using previously published methods. 11,14 The assays complied with the criteria for bioanalytical methods as issued by the European Medicine Agency. 15 The HPLC equipment consisted of a Shimadzu Prominence modular system with a quaternary solvent pump (LC-20AD) with 3 channel degasser (DGU-20 A3R), autosampler (SIL-20AC HT, set at 68C), column oven (CTO-20AC, set at 408C), and SPD-M30 A photodiode array detector, equipped with cells of 10 mm or 85 mm optical path length.…”

“…7 13 The aim of this study was to determine the free plasma concentrations of beta-lactam antibiotics in ICU patients administered as continuous infusion (CI) and to assess the applicability of an ultrafiltration method that mimics physiological conditions (378C/pH 7.4) for routine determination of free drug. 11…”

Importance and Reality of TDM for Antibiotics Not Covered by Insurance in Japan

“…Several methods for the quantification of TZD in plasma using HPLC have been reported [ 69 , 70 , 71 , 77 , 78 , 79 , 80 , 81 , 82 , 83 ]. In Japan, three reports were published in 2020–2021.…”