Development of a simple method for measuring tedizolid concentration in human serum using HPLC with a fluorescent detector

Abstract

The objective of the present study was to develop a method to measure tedizolid (TZD) concentration for studying target concentration intervention, pharmacokinetics, and pharmacodynamics of TZD. We established a high-performance liquid chromatography-fluorescence detector assay to measure the TZD concentration in serum for clinical application. Chromatographic separation was carried out on a 5 μm octadecyl silane hypersil column 150 mm × 4.6 mm. The mobile phase consisted of 0.1 M phosphoric acid and methanol (60:40, pH 7.0). Detection was performed at 300 nm and 340 nm for the excitation and emission wavelengths, respectively. The average retention times of TZD and the internal standard were 12.9 and 8.8 min, respectively. High linearity was exhibited over a concentration range of 0.025 to 10.0 μg/mL for TZD ( R 2 > 0.999). The intra- and inter-assay accuracies of TZD were 99.2% to 107.0% and 99.2% to 107.7%, respectively. The lower limit of quantitation and the lower limit of detection for TZD measurement were 0.025 and 0.01 μg/mL, respectively. The extraction recoveries of TZD were 100.4% to 114.1%. The high-performance liquid chromatography method developed in this study could separate the analytes with a single eluent (isocratic system), within a total run time of 15 min. Both TZD and IS were well separated, without interference from the peaks. Sharp peaks were observed in the chromatograms; problems such as double peaks, shoulder peaks, and broadened peaks were not observed. The proposed method showed acceptable analytical performance and could be used to evaluate serum TZD concentrations in patients.

High feasibility of salivary therapeutic drug monitoring in linezolid, but less in tedizolid: A single-dose study in healthy subjects

“…For tedizolid, the mean (range) tedizolid saliva-to-unbound serum concentration ratio was 0.39 (0.07-0.74), suggesting lower passage into the saliva than linezolid. As in previous studies (29,32), the serum protein-binding rates were different between linezolid and tedizolid in the present study. The median (IQR) serum protein-binding rates are 18.2 (15.8-19.8) in linezolid and 60.3 (48.0-71.1) in tedizolid, respectively (Table 1).…”

“…Total and unbound serum concentrations of linezolid and tedizolid were measured using the improved methodology based on our previously published high-performance liquid chromatography (HPLC) methods (30, 32). Saliva samples were applied in the same manner as serum to measure saliva concentration.…”

Synovial fluid and plasma concentrations of tedizolid in patients with osteoarthritis infected with Staphylococcus aureus effectively determined with fluorescence detection

“…Validated, simple, or enantio-separation of tedizolid using high-performance liquid chromatography has been proposed with tandem mass spectrometry, ultraviolet, or fluorescence detection [ 12 , 13 ]. Relatively good penetration of tedizolid into the interstitial fluid of adipose and muscle tissues has been demonstrated in healthy volunteers [ 9 ], whereas inadequate plasma-to-cerebrospinal fluid ratios of 54% have been reported for tedizolid [ 7 ].…”

“…Synovial fluid and plasma levels of tedizolid were measured using a reversed-phase, high-performance, liquid chromatography system (Shimadzu, Kyoto, Japan) with a Mightysil RP-18GP Aqua column (5 μm, 150 × 4.6 mm, Kanto Chemical, Tokyo, Japan) equilibrated in a mobile phase comprising 35% CH 3 CN in 0.1% aqueous phosphoric acid at a flow rate of 1.0 mL/min and a column temperature of 45 °C. Fluorescence monitoring was carried out at excitation and emission wavelengths of 300 and 340 nm [ 12 ], respectively, and ultraviolet monitoring was done at 254 nm. The samples (10 µL) were infused using an autosampler.…”

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

“…Finally, Tsuji et al reported the quantification of serum TZD concentrations using high-performance liquid chromatography-fluorescence (HPLC-FL) [ 84 ]. High linearity with R 2 > 0.999 was exhibited over a concentration range from 0.025 to 10 μg/mL for TZD.…”