LC method for therapeutic drug monitoring of levetiracetam: Evaluation of the assay performance and validation of its application in the routine area

ObjectivesAn accurate and precise high-performance liquid chromatographic method using diode array detection for the determination of levetiracetam in human plasma has been developed and validated for use in pharmacokinetic studies.MethodsA harmonized validation strategy based on the accuracy profiles was used to select the most appropriate regression model and to determine the limits of quantitation as well as the concentration range of the developed analytical procedure. On the other hand, the present paper also shows this validation approach as a suitable tool to guaranty the quality of the results obtained by the use of the analytical validated methodology for plasma levetiracetam determination in a routine setting and to ensure the risk of obtaining the future measurements outside the previously fixed acceptance limits.ResultsAs pointed recently, the FDA, a weighted 1/x² quadratic regression model ranging from 0.53 to 107.00 mg/L was selected as the simplest calibration model that maximized the accuracy all over the range. Relative bias was < 5%, assay imprecision was always < 6% and mean extraction recovery from plasma was > 90%. So, accuracy did not exceed the acceptance limits settled at ± 20% according to the FDA or Washington conference regulatory requirements for bioanalytical methods. Internal quality control has been assessed over a 2 year time period. All controls were essentially found to provide levetiracetam concentrations within the target range according to the FDA.ConclusionsThe validated analytical procedure complies with strongest regulatory standards. The validated method has a sufficiently rapid turnaround time and their results are good enough to enable the laboratory to routinely provide useful and accurate pharmacokinetic data in time to adjust patient regimens.     

Hemodynamic,respiratory, and perfusion parameters during asphyxia,resuscitation, and post-resuscitation in a pediatric model of cardiac arrest

Purpose  

To analyze the evolution of hemodynamic, respiratory, and tissue perfusion parameters in an infant animal model of asphyxial cardiac arrest (CA).     

Atypical cilia in the bronchiolar epithelium of pigs experimentally infected with hog cholera virus.

To study the effect of hog cholera virus on the epithelial cells of the bronchiolar mucosa, 12 pigs were inoculated with a highly virulent strain. Immunohistochemical and ultrastructural examination of the ciliated epithelial cells demonstrated an increase in the number of atypical cilia. The latter showed alterations in the microtubular pattern, possibly resulting from viral interference with the normal metabolism of the epithelial cells.     

Titanium - castor oil based polyurethane composite foams for bone tissue engineering

Abstract

Polyurethanes (PU) foams with titanium particles (Ti) were prepared with castor oil (CO) and isophorone diisocyanate (IPDI) as polymeric matrix, and 1, 3 and 5?wt.% of Ti. Composites were physicochemically and mechanically characterized and their biocompatibility assessed using human dental pulp stem cells (HDPSC). PU synthesis was confirmed by FTIR, but the presence of Ti was detected by RAMAN, X-ray diffraction (peak at 2θ?=?40.2°) and by EDX-mapping. Materials showed three decomposition temperatures between 300?°C and 500?°C and their decomposition were not catalyzed by Ti particles. Compressive modulus (164–846?kPa), compressive strength (12.9–116.7?kPa) and density (128–240?kg/m³) tend to increase with Ti concentration but porosity was reduced (87% to 80%). Composites’ foams were fully degraded in acid and oxidative media while remained stable in distilled water. HDPSC viability on all composites was higher than 80% up to 14?days while proliferation dropped up to 60% at 21?days. Overall, these results suggest that these foams can be used as scaffolds for bone tissue regeneration.