Rapid detection and identification of impurities in ten 2-naphthalenamines using an atmospheric pressure solids analysis probe in conjunction with ion mobility mass spectrometry.

The atmospheric pressure solids analysis probe (ASAP), in conjunction with ion mobility time-of-flight mass spectrometry (IM-ToF-MS), has been applied to the impurity profiling study of ten 2-naphthalenamines. The impurity profiles achieved by ASAP-IM-MS were compared with those obtained by liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS). All the impurities at the level of 0.1 area % and above, except for one, detected by LC-ESI-MS, were also found by ASAP-IMS analyses. In addition, one non-polar compound was detected by ASAP-IM-MS alone. The IM-MS plot of ion drift time versus m/z values offered sufficient separation between the impurities with different m/z. Therefore, instead of LC as a separation tool, IM-MS is able to provide fingerprint profiling for the ten samples analysed. The time of each analysis has been reduced from 25 min by LC-MS to less than 3 min by ASAP-IM-MS. When collision energy was applied for the selected precursor ion in the transfer T-wave, a clean MS/MS spectrum was obtained for structural elucidation of unknown impurities. The hyphenation of ASAP and IM-MS techniques represents a highly efficient approach for rapid detection and identification of impurities generated in complex reactions involved in pharmaceutical development.

Pharmaceuticals in source separated sanitation systems: Fecal sludge and blackwater treatment.

This study investigated, for the first time, the occurrence and fate of 29 multiple-class pharmaceuticals (PhACs) in two source separated sanitation systems based on: (i) batch experiments for the anaerobic digestion (AD) of fecal sludge under mesophilic (37 °C) and thermophilic (52 °C) conditions, and (ii) a full-scale blackwater treatment plant using wet composting and sanitation with urea addition. Results revealed high concentrations of PhACs in raw fecal sludge and blackwater samples, with concentrations up to hundreds of µg L-1 and µg kg-1 dry weight (dw) in liquid and solid fractions, respectively. For mesophilic and thermophilic treatments in the batch experiments, average PhACs removal rates of 31% and 45%, respectively, were observed. The average removal efficiency was slightly better for the full-scale blackwater treatment, with 49% average removal, and few compounds, such as atenolol, valsartan and hydrochlorothiazide, showed almost complete degradation. In the AD treatments, no significant differences were observed between mesophilic and thermophilic conditions. For the full-scale blackwater treatment, the aerobic wet composting step proved to be the most efficient in PhACs reduction, while urea addition had an almost negligible effect for most PhACs, except for citalopram, venlafaxine, oxazepam, valsartan and atorvastatin, for which minor reductions (on average 25%) were observed. Even though both treatment systems reduced initial PhACs loads considerably, significant PhAC concentrations remained in the treated effluents, indicating that fecal sludge and blackwater fertilizations could be a relevant vector for dissemination of PhACs into agricultural fields and thus the environment.

The Oncolytic Efficacy and in Vivo Pharmacokinetics of [2-(4-Chlorophenyl)quinolin-4-yl](piperidine-2-yl)methanol (Vacquinol-1) Are Governed by Distinct Stereochemical Features.

Glioblastoma remains an incurable brain cancer. Drugs developed in the past 20 years have not improved the prognosis for patients, necessitating the development of new treatments. We have previously reported the therapeutic potential of the quinoline methanol Vacquinol-1 (1) that targets glioblastoma cells and induces cell death by catastrophic vacuolization. Compound 1 is a mixture of four stereoisomers due to the two adjacent stereogenic centers in the molecule, complicating further development in the preclinical setting. This work describes the isolation and characterization of the individual isomers of 1 and shows that these display stereospecific pharmacokinetic and pharmacodynamic features. In addition, we present a stereoselective synthesis of the active isomers, providing a basis for further development of this compound series into a novel experimental therapeutic for glioblastoma.