tedizolid and pazufloxacin

Since severe infections frequently cause acute kidney injury (AKI), continuous renal replacement therapy (CRRT) is often initiated for regulation of inflammatory mediators and renal support. Thus, it is necessary to decide the antibiotic dosage considering the CRRT clearance in addition to residual renal function. Some of the hemofilters used in CRRT are known to adsorb antibiotics, and clearance of antibiotics may differ depending on the adsorptive characteristics of hemofilters. Although assay systems for blood and CRRT filtrate concentrations are required, no method for measuring antibiotics concentrations in filtrate has been reported. We developed a UHPLC-MS/MS method for simultaneous quantification of antibiotics commonly used in ICU, comprising carbapenems [doripenem (DRPM) and meropenem (MEPM)], quinolones [ciprofloxacin (CPFX), levofloxacin (LVFX) and pazufloxacin (PZFX)] and anti-MRSA agents [linezolid (LZD), and tedizolid (TZD)] in CRRT filtrate samples.. Filtrate samples were pretreated by protein precipitation. The analytes were separated with an ACQUITY UHPLC CSH C18 column under a gradient mobile phase consisting of water and acetonitrile containing 0.1% formic acid and 2 mM ammonium formate.. The method showed good linearity over wide ranges. Within-batch and batch-to-batch accuracy and precision for each drug fulfilled the criteria of the US Food and Drug Administration guidance. The recovery rate was more than 87.20%. Matrix effect ranged from 99.57% to 115.60%. Recovery rate and matrix effect did not differ remarkably between quality control samples at different concentrations.. This is the first report of a simultaneous quantification method of multiple antibiotics in filtrate of CRRT circuit.

Topics: Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Ciprofloxacin; Continuous Renal Replacement Therapy; Doripenem; Humans; Levofloxacin; Linezolid; Meropenem; Tandem Mass Spectrometry

Critically ill patients in intensive care unit (ICU) are susceptible to infectious diseases, thus empirical therapy is recommended. However, the therapeutic effect in ICU patients is difficult to predict due to fluctuation in pharmacokinetics because of various factors. This problem can be solved by developing personalized medicine through therapeutic drug monitoring. However, when different measurement systems are used for various drugs, measurements are complicated and time consuming in clinical practice. In this study, we aimed to develop an assay using ultra-high performance liquid chromatography coupled with tandem mass spectrometry for simultaneous quantification of 12 antimicrobial agents commonly used in ICU: doripenem, meropenem, linezolid, tedizolid, daptomycin, ciprofloxacin, levofloxacin, pazufloxacin, fluconazole, voriconazole, voriconazole N-oxide which is a major metabolite of voriconazole, and posaconazole.. Plasma protein was precipitated by adding acetonitrile and 50% MeOH containing standard and labeled IS. The analytes were separated with an ACQUITY UHPLC CSH C18 column, under a gradient mobile phase consisting of water and acetonitrile containing 0.1% formic acid and 2 mM ammonium formate.. The method fulfilled the criteria of US Food and Drug Administration for assay validation. The recovery rate was more than 84.8%. Matrix effect ranged from 79.1% to 119.3%. All the calibration curves showed good linearity (back calculation of calibrators: relative error ≤ 15%) over wide concentration ranges, which allowed determination of C. We have developed an assay for simultaneous quantification of 12 antimicrobial agents using a small sample volume of 50 μL with a short assay time of 7 min. Our novel method may contribute to simultaneous calculation of pharmacokinetic and pharmacodynamic parameters.

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Azoles; Carbapenems; Chromatography, High Pressure Liquid; Ciprofloxacin; Daptomycin; Doripenem; Drug Monitoring; Female; Fluconazole; Fluoroquinolones; Humans; Intensive Care Units; Levofloxacin; Linezolid; Male; Meropenem; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Oxazines; Oxazolidinones; Quinolones; Tandem Mass Spectrometry; Tetrazoles; Voriconazole