Determination of mitragynine in plasma with solid-phase extraction and rapid HPLC–UV analysis, and its application to a pharmacokinetic study in rat

A new solid phase extraction method for rapid high performance liquid chromatography–UV determination of mitragynine in plasma has been developed. Optimal separation was achieved with an isocratic mobile phase consisting of acetonitrile–ammonium acetate buffer, 50 mM at pH 5.0 (50:50, v/v). The method had limits of detection and quantification of 0.025 and 0.050 μg/mL, respectively. The method was accurate and precise for the quantitative analysis of mitragynine in human and rat plasma with within-day and between-day accuracies between 84.0 and 109.6%, and their precision values were between 1.7 and 16.8%. Additional advantages over known methods are related to the solid phase extraction technique for sample preparation which yields a clean chromatogram, a short total analysis time, requires a smaller amount of plasma samples and has good assay sensitivity for bioanalytical application. The method was successfully applied in pharmacokinetic and stability studies of mitragynine. In the present study, mitragynine was found to be fairly stable during storage and sample preparation. The present study showed for the first time the detailed pharmacokinetic profiles of mitragynine. Following intravenous administration, mitragynine demonstrated a biphasic elimination from plasma. Oral absorption of the drug was slow, prolonged and was incomplete, with a calculated absolute oral bioavailability value of 3.03%. The variations observed in previous pharmacokinetic studies after oral administration of mitragynine could be attributed to its poor bioavailability rather than to the differences in assay method, metabolic saturation or mitragynine dose.     

Performance of Canadian clinical laboratories processing throat culture proficiency testing surveys

Proficiency testing results obtained from simulated throat swab cultures sent between 1999 and 2013 were analyzed to evaluate the ability of participants to process, analyze, and properly report results for these cultures. Eight percent of all pathogen-positive samples were reported as false negatives, and 11 % of the pathogen-negative ones were reported as false positives. More than 90 % of the participants achieved acceptable grades in each of the proficiency testing samples containing Streptococcus pyogenes. Laboratories were less successful in reporting other significant pathogens including group C and G streptococcus and Arcanobacterium haemolyticum, although an overall increase in performance was observed for each subsequent survey. Most laboratories recognized other respiratory pathogens as not being agents of pharyngitis; a common issue with these specimens was the suggestion of the organism’s clinical significance when their presence was reported. The presence of small colony-forming β-hemolytic streptococcus (Streptococcus anginosus group) proved to be challenging for many laboratories as 66 % of all unacceptable grades for pathogen-negative throat swabs occurred in these PT samples. Moreover, performance in this group did not improve with subsequent surveys. Results obtained in this study support the added value of clinical relevancy challenges for proficiency testing as laboratories that may not have problems with the analytical aspect of the testing process struggle with the appropriate interpretation of results.     

Controlling bubbles using bubbles--microfluidic synthesis of ultra-small gold nanocrystals with gas-evolving reducing agents

Microfluidic wet-chemical synthesis of nanoparticles is a growing area of research in chemical microfluidics, enabling the development of continuous manufacturing processes that overcome the drawbacks of conventional batch-based synthesis methods. The synthesis of ultra-small (<5 nm) metallic nanocrystals is an interesting area with many applications in diverse fields, but is typically very challenging to accomplish in a microfluidics-based system due to the use of a strong gas-evolving reducing agent, aqueous sodium borohydride (NaBH(4)), which causes uncontrolled out-gassing and bubble formation, flow disruption and ultimately reactor failure. Here we present a simple method, rooted in the concepts of multiphase mass transfer that completely overcomes this challenge-we simply inject a stream of inert gas bubbles into our channels that essentially capture the evolving gas from the reactive aqueous solution, thereby preventing aqueous dissolved gas concentration from reaching the solubility threshold for bubble nucleation. We present a simple model for coupled mass transfer and chemical reaction that adequately captures device behaviour. We demonstrate the applicability of our method by synthesizing ultra-small gold nanocrystals (<5 nm); the quality of nanocrystals thus synthesized is further demonstrated by their use in an off-chip synthesis of high-quality gold nanorods. This is a general approach that can be extended to a variety of metallic nanomaterials.