Toward the optimization of double-pulse LIBS underwater: effects of experimental parameters on the reproducibility and dynamics of laser-induced cavitation bubble.

Double-pulse laser-induced breakdown spectroscopy (LIBS) was recently proposed for the analysis of underwater samples, since it overcomes the drawbacks of rapid plasma quenching and of large continuum emission, typical of single-pulse ablation. Despite the attractiveness of the method, this approach suffers nevertheless from a poor spectroscopic reproducibility, which is partially due to the scarce reproducibility of the cavitation bubble induced by the first laser pulse, since pressure and dimensions of the bubble strongly affect plasma emission. In this work, we investigated the reproducibility and the dynamics of the cavitation bubble induced on a solid target in water, and how they depend on pulse duration, energy, and wavelength, as well as on target composition. Results are discussed in terms of the effects on the laser ablation process produced by the crater formation and by the interaction of the laser pulse with floating particles and gas bubbles. This work, preliminary to the optimization of the spectroscopic signal, provides an insight of the phenomena occurring during laser ablation in water, together with useful information for the choice of the laser source to be used in the apparatus.

Performance of the new mycophenolate assay based on IMPDH enzymatic activity for pharmacokinetic investigations and setup of Bayesian estimators in different populations of allograft recipients.

A new mycophenolate (MPA) assay based on the enzymatic activity of recombinant type II inosine monophosphate dehydrogenase (the pharmacological target of MPA) with excellent correlation with high-performance liquid chromatography has recently been released for the measurement of MPA plasma levels. This study aimed to (1) compare this new assay with liquid chromatography tandem mass spectrometry (LC-MS/MS) for MPA pharmacokinetic (PK) studies in different populations of allograft recipients given mycophenolate mofetil, (2) develop specific Bayesian estimators for this inhibition assay and test their accuracy, and (3) compare the resulting MPA area under the curve (AUC0-12h) estimates with those of Bayesian estimators developed based on the LC-MS/MS results. Sixty-four adult or pediatric, renal or lung transplant patients who were administered mycophenolate mofetil in association with cyclosporine, tacrolimus, or sirolimus at different post-transplant periods were enrolled as part of different PK studies. Eight hundred ninety-four patients' samples were analyzed in parallel with the enzymatic MPA assay and a reference LC-MS/MS method. Repeated analysis of quality control samples showed a mean difference of 6% between the 2 assays, whereas the results obtained in different populations of transplanted patients showed excellent correlation (r2 > 0.96) and small mean relative differences (2.0%-16.9%). The full profiles obtained with both assays were adequately fitted using either a 2-compartment model with 1 "gamma" absorption phase or a 1-compartment model with 2 gamma inputs. Several PK parameters were significantly affected by the analytical method used. Accurate Bayesian estimators could be specifically developed for the enzymatic MPA assay, using the same 3 concentration-time points (20 minutes, 1 hour, and 3 hours post dose) as with LC-MS/MS, with a median bias versus reference (trapezoidal) AUC0-12h values of -1.3% (range -45.2% to 40.4%), and 83% of the patients within +/-20% of the reference. These Bayesian estimates were significantly higher than those obtained with LC-MS/MS in patients on cyclosporine or sirolimus, but not in patients on tacrolimus.