期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 103, 期 3, 页码 1013-1019出版社
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.23872
关键词
tigecycline; microdialysis; bioanalysis; protein binding; liquid chromatography; mass spectrometry; atypical nonlinear plasma-protein binding
Tigecycline, a novel glycylcycline antibiotic, shows atypical nonlinear plasma-protein-binding behavior using ultrafiltration and ultracentrifugation techniques. The mechanism of such counterintuitive behavior is currently unknown. Ultrafiltration and ultracentrifugation cause fractional change in protein concentration and therefore may influence plasma-protein binding. Microdialysis (MD), a novel technique, can sample unbound drugs without any change in fractional protein concentration. To determine whether the atypical nonlinear plasma-protein-binding behavior is not related to measurement technique, the plasma-protein binding of tigecycline was determined using MD. A sensitive liquid chromatography-mass spectrometry method was developed and validated for the bioanalysis of tigecycline in the dialysate. The probe recoveries and plasma-protein binding of tigecycline at four different concentration levels 0.1, 1, 10, and 100 g/mL were determined. Similar to ultracentrifugation and ultrafiltration, MD also showed atypical nonlinear plasma-protein-binding behavior of tigecycline up to 10 g/mL, but unbound fraction increased at 100 g/mL indicating saturation of mechanism responsible for atypical nonlinear behavior. This study concludes that the atypical nonlinear binding behavior of tigecycline is not technique-dependent, rather it is a true behavior of tigecycline. Further investigations are necessary to elucidate the mechanism. (c) 2014 Wiley Periodicals, Inc.
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