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A micellar electrokinetic chromatography method for simultaneous assay of ticarcillin and clavulanic acid in Timentin i.v. injection preparation was developed. This method ensures excellent separation of both components of Timentin preparation. The validation of the method was performed, and specificity, reproducibility, precision and accuracy were confirmed. The detection and quantitative limits for Timentin were established in the concentrations 0.04 and 0.08 mg/ml, respectively. The elaborated technique was compared with two methods routinely used-UV and high performance liquid chromatography (HPLC). The obtained results and their statistical analysis proved the same precision of all methods, however, no significant differences were observed between CE and HPLC. [Copyright &y& Elsevier]

Abstract: Linezolid is the first compound of a truly new class of antibiotics—the oxazolidinones. The elaborated method of capillary electrophoresis (CE) of linezolid separation from its achiral impurities was successfully performed using sweeping preconcentration, followed by UV absorption detection at 254nm. The best results were obtained with 125mM Tris buffer, pH 2.0, with addition of 20% (v/v) methanol as background electrolyte. Sodium dodecyl sulfate (150mM) was added to the electrolyte in the inlet vial as the sweeping agent. The separation was carried out at negative polarity. Then, the optimized method was validated in terms of linearity, accuracy and precision. Sweeping preconcentration of linezolid provides detection limit at 0.05μg/ml level. The evaluated CE method was applied in the analysis of medicinal product containing linezolid–linezolid solution for infusion. [Copyright &y& Elsevier]

A rapid, capillary electrophoresis method was evaluated for determination of amoxicillin and clavulanic acid in Augmentin as well as ampicillin and sulbactam in Unasyn preparations for injections. Phosphate–borate buffer at pH 8.66 containing 14.4% sodium dodecyl sulfate was used as a mobile phase. The method was validated. Reproducibility, precision, accuracy and assay linearity in concentration of amoxicillin 0.05–3.03 mg/ml and ampicillin 0.05–3.08 mg/ml, as well as clavulanic acid 0.02–2.02 mg/ml and sulbactam 0.05–2.08 mg/ml were established. This new method is fast, inexpensive and limits consumption of organic solvents when compared with alternative high performance liquid chromatography (HPLC) method, used for drug analysis. Statistical analysis by Student''s t-test showed no significant differences between the results obtained by the two methods tcalculated 0.32 and 1.69 for amoxicillin and clavulanic acid and 0.67 and 1.93 for ampicillin and sulbactam were smaller than ttabulated. [Copyright &y& Elsevier]

A series of 22 benzosiloxaboroles, silicon analogues of strong antimicrobial agents - benzoxaboroles, have been synthesized and tested against β-lactamases KPC- and pAmpC-producing strains of Gram-negative rods. Comprehensive structural-property relationship studies supported by molecular modelling as well as biological studies reveal that 6-B(OH) 2 -substituted derivative 27 strongly inhibits the activity of cephalosporinases (chromosomally encoded AmpC and plasmid encoded CMY-2) and KPC carbapenemases. It also shows strong ability to inhibit growth of the strains producing KPC-3 when combined with meropenem. In addition, halogen-substituted (mono-, di- or tetra-) benzosiloxaboroles demonstrate high antifungal activity (MIC 1.56–6.25 mg/L) against C. tropicalis , C. guilliermondii and S. cerevisiae. The highest activity against pathogenic yeasts (C. albicans , C. krusei and C. parapsilosis - MICs 12.5 mg/L) and against Gram-positive cocci (S. aureus and E. faecalis - 6.25 mg/L and 25 mg/L respectively) was displayed by 6,7-dichloro-substituted benzosiloxaborole. The studied systems exhibit low cytotoxity toward human lung fibroblasts. Image 1 • Synthesis and characterization of a series of 22 functionalized benzosiloxaboroles. • Strong antifungal activity of fluorinated derivatives. • KPC/AmpC inhibitory activity of selected benzosiloxaboroles. • Docking and molecular dynamics studies on the binding to the KPC-2 β-lactamase. [ABSTRACT FROM AUTHOR]

Ceftaroline fosamil, the prodrug of ceftaroline, is an advanced-generation cephalosporin antibacterial agent approved for treatment in the European Union in 2012. The drug is dedicated to curing complicated skin and soft tissue infections and community-acquired pneumonia. The developed analytical method of high performance liquid chromatography (HPLC) followed by diode array detector (DAD) set at 243 nm was used to identify and determine degradation products of ceftaroline fosamil. The elaborated method demonstrated good selectivity and linearity [r > 0.998 for the range 0.8–1.2 mg/mL (80–120%) and r > 0.997 for the range 0.005–0.015 mg/mL (0.5–1.5%)]. Limit of detection (LOD) and limit of quantification (LOQ) values were equal to 0.15 μg/mL and 0.5 μg/mL, respectively. The forced decomposition of ceftaroline fosamil carried out under acidic, basic, oxidative, photolytic and thermal conditions revealed the high sensitivity of ceftaroline on photodegradation and thermolysis processes. Representative ceftaroline samples were selected and analysed by LC coupled with electrospray ionisation time-of-flight mass spectrometry (LC-ESI-Q-TOF-MS) to identify the related substances that appeared under stress conditions. The LC-DAD method was transferred without any modification to LC–MS/MS system, allowing it to correlate results back to the LC-DAD method. Eight unknown signals were detected in the photolytic and thermal stress solutions for ceftaroline fosamil. The evaluated method was applied to the analysis of a medicinal product containing ceftaroline fosamil − Zinforo™, 600 mg, powder for concentrate for solution for infusion. Moreover, the optimised conditions allowed for the successful separation of eight cephalosporin antibiotics possessing a molecular structure similar to ceftaroline (cefepime, cefapirin, ceftazidime, cefpirome, cefalonium, cefotaxime, cefquinome, cefalotin). [ABSTRACT FROM AUTHOR]

Abstract: The oxazolidinones are a new and potent class of antimicrobial agents with activity mainly against Gram-positive strains. The commercial success of linezolid, the only FDA-approved oxazolidinone, has prompted many pharmaceutical companies to devote resources to this area of investigation. Until now, four types of chemical modifications of linezolid and oxazolidinone-type antibacterial agents, including modification on each of the A-(oxazolidinone), B-(phenyl), and C-(morpholine) rings as well as the C-5 side chain of the A-ring substructure, have been described. Division into sections according to side chain modification or the type of ring will be used throughout this review, although the process of synthesis usually involves the simultaneous modification of several elements of the linezolid substructure; therefore, assignment into the appropriate section depends on the structure–activity relationships (SAR) studies. This review makes an attempt to summarise the work carried out in the period from 2006 until mid-2012. [Copyright &y& Elsevier]

• 12 new degradation products and three new by-products were identified. • fragmentation pathways were proposed for related compounds. • structure elucidation was performed by high resolution mass spectrometry (HRMS). • the kinetics and shelf-life values in solution-state studies were determined. • activation energies were calculated for alkaline and thermolytic degradation. The aim of the study was to investigate the intrinsic stability and to identify potential degradation products of tedizolid disodium phosphate (TED-OPO 3 Na 2), which belongs to the antimicrobial agents of the oxazolidinone class. Tedizolid, as disodium phosphate (prodrug), is registered under the trade name SIVEXTRO®, at a dose of 200 mg, in the form of powder for injection or infusion. The stability-indicating assay method was optimised using HPLC with diode array detection and with electrospray ionisation time-of-flight mass spectrometry. In solution-state studies, the forced decomposition of TED-OPO 3 Na 2 carried out under acidic, basic, oxidative, photocatalytic, and thermal conditions revealed the lability of TED-OPO 3 Na 2 to acidic, basic, and photocatalytic (UV) conditions, while it was relatively stable in oxidative conditions and during thermolysis processes. The kinetics of degradation and shelf-life values in solution-state studies were determined, and activation energies were calculated for alkaline and thermolytic degradation. In contrast, in the solid state degradation study, TED-OPO 3 Na 2 was stable under thermal conditions at high humidity and in visible light, while moderate degradation was observed under thermal conditions of low humidity and ultraviolet light. The developed method enabled the identification of 12 new degradation products and 3 new by-products. [ABSTRACT FROM AUTHOR]