Kinetic Study on the Base-Catalyzed Imine-Enamine Tautomerism of a Chiral Biologically Active Isoxazoline Derivative by HPLC on Amylose Tris(3,5-dimethylphenylcarbamate) Chiral Stationary Phase.

Isoxazoline is a nitrogen- and oxygen-containing five-membered heterocyclic scaffold with diverse biological profiles such as antimicrobial, fungicidal, anticancer, antiviral, analgesic and anti-inflammatory activity. Accordingly, the use of this peculiar structural framework in drug discovery is a successful strategy for the development of new drug candidates. Here, a chiral saccharin/isoxazoline hybrid was considered to investigate the tendency of the imine moiety of the heterocyclic ring to tautomerize to the enamine form in the presence of a basic catalyst. The pseudo-first-order rate constants for the base-catalyzed tautomerization process were measured in different solvents and at different temperatures by off-column kinetic experiments based on the amylose (3,5-dimethylphenylcarbamate)-type chiral stationary phase. The kinetic results obtained in this study may be a useful aid in the perspective of designing experimental conditions to control the stereointegrity of these types of pharmacologically active compounds and drive their synthesis toward the preferred, imine or enamine, tautomer.

Estimation of legal and illegal drugs consumption in Valencia City (Spain): 10 years of monitoring.

Wastewater-based epidemiology (WBE) approach provides objective, quantitative, near real-time profiles of illicit drug consumption by monitoring the concentration of unchanged parent drugs or their metabolites entering the municipal sewage system. Valencia is the third most populous city in Spain (an important country for the use and transit of several of these drugs). Estimations of consumption over long periods of time will help get better understanding of spatial and temporal trends in the use of licit and illicit drugs. Accordingly, applying the "best practice" protocol, 16 drugs of abuse and metabolites were monitored in this study, and 8 were daily measured during one-two weeks between 2011 and 2020 at the inlet of three wastewater treatment plants of Valencia City. Analysis of the selected compounds was performed by liquid chromatography-triple quadrupole mass spectrometry, and the concentrations obtained were used to back-calculate the consumption data. Cannabis, tobacco, and cocaine were the most consumed drugs whereas opioids were less used. Cannabis and cocaine consumption are on average 2.7-23.4 and 1.1-2.3 g/day/1000inh, respectively, and their use tended to increase since 2018. Weekly profiles were characterized by higher consumption of cocaine, ecstasy, and heroin during weekends compared to weekdays. Similarly, during "Las Fallas" (main local festivity), increased use of cocaine and amphetamine-type stimulants, mainly MDMA, was measured. WBE proved to be an objective and useful methodology to get more insight on temporal drugs of abuse consumption, and the changes derived from local festivities.

Non-Occupational Exposure to Pesticides: Experimental Approaches and Analytical Techniques (from 2019).

BACKGROUND: Pesticide residues are a threat to the health of the global population, not only to farmers, applicators, and other pesticide professionals. Humans are exposed through various routes such as food, skin, and inhalation. This study summarizes the different methods to assess and/or estimate human exposure to pesticide residues of the global population. METHODS: A systematic search was carried out on Scopus and web of science databases of studies on human exposure to pesticide residues since 2019. RESULTS: The methods to estimate human health risk can be categorized as direct (determining the exposure through specific biomarkers in human matrices) or indirect (determining the levels in the environment and food and estimating the occurrence). The role that analytical techniques play was analyzed. In both cases, the application of generic solvent extraction and solid-phase extraction (SPE) clean-up, followed by liquid or gas chromatography coupled to mass spectrometry, is decisive. Advances within the analytical techniques have played an unquestionable role. CONCLUSIONS: All these studies have contributed to an important advance in the knowledge of analytical techniques for the detection of pesticide levels and the subsequent assessment of nonoccupational human exposure.

Analytical and semipreparative high performance liquid chromatography enantioseparation of bicalutamide and its chiral impurities on an immobilized polysaccharide-based chiral stationary phase.

Direct HPLC separation of enantiomers of Bicalutamide (BCT), a non-steroidal antiandrogen used for the treatment of prostate cancer, was performed by using the immobilized amylose-based Chiralpak IA chiral stationary phase (CSP). Enantioselective conditions were achieved using standard normal phase mixtures n-hexane-alcohol (ethanol or 2-propanol) and a "non-standard" mobile phase containing ethyl acetate (EA). The chromatographic behaviour of the IA CSP under these elution modes was evaluated and compared at different temperatures. The eluent mixture n-hexane-EA-ethanol 100-30-5 (v/v/v) and the column temperature of 40°C were identified as the best operational conditions to carry out semipreparative enantioseparations on a 1-cm I.D. IA column. Using this protocol, about 960mg of (R)-BCT, which is the enantiomer with the almost entire anti-androgenic activity of BCT, per day could be isolated. The analytical and semipreparative HPLC resolution of chiral impurities of BCT, and their empiric absolute configuration assignment by circular dichroism correlation method are also presented.