A simple and high‐resolution HPLC‐PDA method for simultaneous quantification of local anesthetics in in vitro buccal permeation enhancement studies

A simple, isocratic, high‐resolution and prompt HPLC‐PDA method was developed and validated for the simultaneous quantification of prilocaine (PCL) and lidocaine (LCL) hydrochlorides in in vitro buccal iontophoresis‐driven permeation studies. A reversed‐phase C₁₈ column (250 mm x 4.6 mm, 3μm, 110Å) was used for the chromatographic separation. The mobile phase contained acetonitrile: 0.1M sodium phosphate buffer, pH 7.0 (1:1, v/v), plus 0.05% (v/v) diethylamine. The isocratic flow rate was set at 1 mL/min and the detection wavelength was 203 nm. PCL and LCL eluted in 8.9 min and 13 min, respectively, and the system suitability parameters varied within an acceptable range. The method was selective, sensitive, precise, accurate and robust, producing a linear plot at the concentration range of 0.25 to 10 µg/mL. The application of this method was demonstrated by a significant enhancement of the permeation of PCL and LCL with the application of iontophoresis (1 mA/cm² per 1 h) through isolated porcine esophageal epithelium. The amount of the drug retained in the epithelium also increased with the application of an electrical current. Copyright © 2015 John Wiley & Sons, Ltd.     

Simple HPLC‐UV for the quantification of a new leishmanicidal candidate (E)‐1‐4(trifluoromethyl) benzylidene)‐5‐(2‐4‐dichlorozoyl) carbonylhydrazine (LASSBio‐1736) in rat plasma for pharmacokinetics assessment

In this study, a sensitive HPLC‐UV assay was developed and validated for the determination of LASSBio‐1736 in rat plasma with sodium diclofenac as internal standard (IS). Liquid–liquid extraction using acetonitrile was employed to extract LASSBio‐1736 and IS from 100 μL of plasma previously basified with NaOH 0.1 M. Chromatographic separation was carried on Waters Spherisorb^®S5 ODS2 C₁₈ column (150 × 4.6 mm, 5 μm) using an isocratic mobile phase composed by water with triethylamine 0.3% (pH 4), methanol and acetonitrile grade (45:15:40, v/v/v) at a flow rate of 1 mL/min. Both LASSBio‐1736 and IS were eluted at 4.2 and 5 min, respectively, with a total run time of 8 min only. The lower limit of quantification was 0.2 μg/mL and linearity between 0.2 and 4 μg/mL was obtained, with an R² > 0.99. The accuracy of the method was >90.5%. The relative standard deviations intra and interday were <6.19 and <7.83%, respectively. The method showed the sensitivity, linearity, precision, accuracy and selectivity required to quantify LASSBio‐1736 in preclinical pharmacokinetic studies according to the criteria established by the US Food and Drug Administration and European Medicines Agency. Copyright © 2016 John Wiley & Sons, Ltd.     

Gutmann's Donor Numbers Correctly Assess the Effect of the Solvent on the Kinetics of SNAr Reactions in Ionic Liquids

We report an experimental study on the effect of solvents on the model S_NAr reaction between 1‐chloro‐2,4‐dinitrobenzene and morpholine in a series of pure ionic liquids (IL). A significant catalytic effect is observed with reference to the same reaction run in water, acetonitrile, and other conventional solvents. The series of IL considered include the anions, NTf₂^?, DCN^?, SCN^?, CF₃SO₃^?, PF₆^?, and FAP^? with the series of cations 1‐butyl‐3‐methyl‐imidazolium ([BMIM]⁺), 1‐ethyl‐3‐methyl‐imidazolium ([EMIM]⁺), 1‐butyl‐2,3‐dimethyl‐imidazolium ([BM₂IM]⁺), and 1‐butyl‐1‐methyl‐pyrrolidinium ([BMPyr]⁺). The observed solvent effects can be attributed to an “anion effect”. The anion effect appears related to the anion size (polarizability) and their hydrogen‐bonding (HB) abilities to the substrate. These results have been confirmed by performing a comparison of the rate constants with Gutmann's donicity numbers (DNs). The good correlation between rate constants and DN emphasizes the major role of charge transfer from the anion to the substrate.     

Unprecedented Double aza‐Michael Addition within a Sapphyrin Core

A novel sapphyrin derivative was obtained from the reaction between a free‐base sapphyrin and dimethyl acetylenedicarboxylate (DMAD). The formation of the new compound involved a double aza‐Michael addition of two pyrrolic NH groups to a DMAD molecule, with the formation of a disubstituted ethano bridge. The NMR spectral data reveal a product with an unsymmetrical structure; DFT calculations provided support for a structure in which the ethano bridge links two adjacent pyrrole units. The present study provides a seemingly unprecedented example of an N,N′‐dinucleophile reacting with DMAD to form a heterocyclic compound in which the two N‐atoms are linked to the two sp³ carbon atoms derived from a substituted acetylene.     

Exploring the Reactivity of α‐Lithiated Aryl Benzyl Ethers: Inhibition of the [1,2]‐Wittig Rearrangement and the Mechanistic Proposal Revisited

By carefully controlling the reaction temperature, treatment of aryl benzyl ethers with tBuLi selectively leads to α‐lithiation, generating stable organolithiums that can be directly trapped with a variety of selected electrophiles, before they can undergo the expected [1,2]‐Wittig rearrangement. This rearrangement has been deeply studied, both experimentally and computationally, with aryl α‐lithiated benzyl ethers bearing different substituents at the aryl ring. The obtained results support the competence of a concerted anionic intramolecular addition/elimination sequence and a radical dissociation/recombination sequence for explaining the tendency of migration for aryl groups. The more favored rearrangements are found for substrates with electron‐poor aryl groups that favor the anionic pathway.     

Advanced Sensing of Antibiotics with Magnetic Gold Nanocomposite: Electrochemical Detection of Chloramphenicol

The sensing and accurate determination of antibiotics in various environments represents a big challenge, mainly owing to their widespread use in medicine, veterinary practice, and other fields. Therefore, a new, simple electrochemical sensor for the detection of antibiotic chloramphenicol (CAP) has been developed in this work. The amplification strategy of the sensor is based on the application of magnetite nanostructures stabilized with carboxymethyl cellulose (Fe₃O₄‐CMC) and decorated with nanometer‐sized Au nanoparticles (NPs) (Fe₃O₄‐CMC@Au). In this case, CMC serves as a stabilizing agent, preventing the aggregation of Fe₃O₄ NPs, and hence, enabling the kinetic barrier for electron transport to be overcome, and the Au NPs serve as an electron‐conducting tunnel for better electron transport. As a proof of concept, the developed nanosensor is used for the detection of CAP in human urine samples, giving a recovery value of around 97 %, which indicates the high accuracy of the as‐prepared nanosensor.