Capillary electrophoresis for the analysis of antidepressant drugs: A review

Depression is a common mental disorder that may lead to major mental health problems, and antidepressant drugs have been used as a treatment of choice to mitigate symptoms of major depressive disorders by ameliorating the chemical imbalances of neurotransmitters in brain. Since abusing antidepressant drugs such as selective serotonin reuptake inhibitors and tricyclic antidepressant drugs can cause severe adverse effects, continuous toxicological monitoring of the parent compounds as well as their metabolites using numerous analytical methods appears pertinent. Among them, capillary electrophoresis has been popularly utilized since the method has a lot of advantages viz. using small amounts of sample and solvents, ease of operation, and rapid analysis. This review paper brings a survey of more than 30 papers on capillary electrophoresis of antidepressant drugs published approximately from 1999 until 2018. It focuses on the reported capillary electrophoresis techniques and their applications and challenges for determining antidepressant drugs and their metabolites. It is organized according to the commonly used capillary zone electrophoresis method, followed by non‐aqueous capillary electrophoresis and micellar electrokinetic chromatography, with details on breakthrough findings. Where available, information is given about the background electrolyte used, detector utilized, and sensitivity obtained.     

Development of XIAP Antagonists Based On De Novo 8,5-Fused Bicyclic Lactams

In order to develop original water soluble antagonists of X-linked inhibitor of apoptosis protein (XIAP), a novel bicyclic scaffold was designed based on 8,5-fused bicyclic lactam. During its preparation, a spontaneous rearrangement from 8,5- to 7,5-fused bicyclic lactam was observed and confirmed by MS and NMR analyses, in particular the HMBC spectra. DFT calculations were performed to understand the corresponding mechanism. It was finally prevented through changing the reaction order in the synthesis route and a Smac mimetic with this core structure, ZJ-1 was successfully obtained. The structure of this new bicyclic scaffold was well confirmed by HRMS and NMR (¹H, ¹³C, NOESY) analyses. ZJ-1 presented in addition a binding affinity to XIAP-BIR3, nearly 6 times better than that of AVPI, similar to the reported SM-128 in an in vitro fluorescence polarization (FP) assay. This preliminary result suggests that this new bicyclic scaffold could be very attractive in the development of novel anticancer agents targeting XIAP.     

Development and validation of a liquid chromatography–tandem mass spectrometry analytical method for the therapeutic drug monitoring of eight novel anticancer drugs

To support therapeutic drug monitoring of patients with cancer, a fast and accurate method for simultaneous quantification of the registered anticancer drugs afatinib, axitinib, ceritinib, crizotinib, dabrafenib, enzalutamide, regorafenib and trametinib in human plasma using liquid chromatography tandem mass spectrometry was developed and validated. Human plasma samples were collected from treated patients and stored at −20°C. Analytes and internal standards (stable isotopically labeled analytes) were extracted with acetonitrile. An equal amount of 10 mm NH₄CO₃ was added to the supernatant to yield the final extract. A 2 μL aliquot of this extract was injected onto a C₁₈‐column, gradient elution was applied and triple‐quadrupole mass spectrometry in positive‐ion mode was used for detection. All results were within the acceptance criteria of the latest US Food and Drug Administration guidance and European Medicines Agency guidelines on method validation, except for the carry‐over of ceritinib and crizotinib. These were corrected for by the injection order of samples. Additional stability tests were carried out for axitinib and dabrafenib in relation to their reported photostability. In conclusion, the described method to simultaneously quantify the eight selected anticancer drugs in human plasma was successfully validated and applied for therapeutic drug monitoring in cancer patients treated with these drugs.     

TiO2@C Nanostructured Electrodes for the Anodic Removal of Cocaine

The generalization use of therapeutic and illicit drugs are introducing new several chemical pollutants in water. They have been detected in water and sewage samples worldwide, hence they are considered as emerging pollutants. The increase of water threats has a negative impact on the life quality and human health. Among the illicit drugs, cocaine and derivatives are increasingly present, making efficient detection and elimination of wastewater highly prioritaire. In that sense, the main core of this work is the assessment of a novel cost‐efficient electrochemical method based on substrate electro‐oxidation (EO) using low‐cost anodes based on common graphite modified with TiO₂ nanosized particles incorporated on the surface by assisted microwave deposition. Two different diameters (2 and 5 nm) of nanostructured TiO₂@C anodes were tested for cocaine EO reaction using three different electrolytic solutions (NaCl 50 mM, Na₂SO₄ 50 mM or Na₂SO₄ 100 mM). In all cases, the electrochemical oxidation of cocaine appears to be a combination of hypsochromic and hyperchromic processes. Reaching ca. 90 % degradation after 10 minutes for all electrodes, an enhanced efficiency was especially observed for the system with higher cylindrical diameter and NaCl salt medium. The differential pulse (DP) voltammogram, carried out with all assay solutions after 10 minutes of anodic remediation at both electrodes, exhibited an anodic peak consistent with catechol like compounds.     

Veterinary antimicrobials and antiparasitics in fee-fishing ponds: analytical method and occurrence*

ABSTRACT

The aim of this work was to develop and validate a method using online solid-phase extraction and ultra-high-performance liquid chromatography coupled to tandem mass spectrometry to determine residues of 22 veterinary drugs including sulfonamides, amphenicols, fluoroquinolones, benzimidazoles, trimethoprim (TMP) and oxytetracycline (OTC) in water from fee-fishing ponds. The optimal analytical conditions were as follows: XBridge C8 SPE column, Acquity UPLC CSH C18 analytical column, sample loading with water:methanol (98:2, v/v), mobile phase of water with 0.1% acetic acid:methanol (with gradient elution) and eluent flow rate of 0.3 mL min^?1. Quantification was performed in selected reaction monitoring mode and sulfadimethoxine-d₆, ciprofloxacin-d₈, florfenicol-d₃ and albendazole-d₃ were used as internal standards. Water samples collected from 11 fee-fishing ponds showed the presence of residues of FF (0.42–0.74 µg L^?1), albendazole (0.05–0.31 µg L^?1) and thiabendazole (0.45 µg L^?1). Thiamphenicol and TMP were detected at concentrations lower than the limits of quantification of the method (0.1 and 0.001 µg L^?1, respectively).     

Evaluation of the Stereochemical Lability of Benzo-Cycloheptene-Based Drugs Endowed with Potentially Modulable Planar Chirality

An experimental and theoretical study was carried out to analyze the configurational lability possessed by some of the most common drugs endowed with a central non-planar seven-membered cycloheptadiene ring, which confers chirality to these compounds. In fact, the absence of planarity allows the existence of two enantiomeric species that can interconvert thanks to a ring overturning mechanism. The energy barrier that opposes the inversion of the chiral tricyclic scaffold characterizing such species, which is strongly dependent on the presence of appropriate substituents on the two external cycles, has been investigated through Dynamic-HPLC and off-column racemization techniques, as well as through assessments based on molecular modelling approaches. Interesting indications were obtained by making targeted structural changes to allow accurate control of the stereolability characterizing the tricyclic framework.     

Bisindolylmaleimides New Ligands of CaM Protein

In the present study, we reported the interactions at the molecular level of a series of compounds called Bisindolylmaleimide, as potential inhibitors of the calmodulin protein. Bisindolylmaleimide compounds are drug prototypes derived from Staurosporine, an alkaloid with activity for cancer treatment. Bisindolylmaleimide compounds II, IV, VII, X, and XI, are proposed and reported as possible inhibitors of calmodulin protein for the first time. For the above, a biotechnological device was used (fluorescent biosensor hCaM M124C-mBBr) to directly determine binding parameters experimentally (K_d and stoichiometry) of these compounds, and molecular modeling tools (Docking, Molecular Dynamics, and Chemoinformatic Analysis) to carry out the theoretical studies and complement the experimental data. The results indicate that this compound binds to calmodulin with a K_d between 193–248 nM, an order of magnitude lower than most classic inhibitors. On the other hand, the theoretical studies support the experimental results, obtaining an acceptable correlation between the ΔG_Experimental and ΔG_Theoretical (r² = 0.703) and providing us with complementary molecular details of the interaction between the calmodulin protein and the Bisindolylmaleimide series. Chemoinformatic analyzes bring certainty to Bisindolylmaleimide compounds to address clinical steps in drug development. Thus, these results make these compounds attractive to be considered as possible prototypes of new calmodulin protein inhibitors.     

Quantification of Arbutin in Cosmetics,Drugs and Food Supplements by Hydrophilic-Interaction Chromatography

Arbutin, the glucoside of hydroquinone, exists in two isomers, α-arbutin and β-arbutin. The synthetic α isomer is mainly used as a skin brightening agent, while β-arbutin occurs naturally, for instance in bearberry, and is used in drugs for treatment of lower urinary tract infections and as a food supplement. Since both isomers can be harmful at high concentrations, methods for their quantification are required. Classically they have been determined by reversed-phase chromatography, but separation of both isomers is often unsatisfactory. Here we present a simple and reliable method for quantification of α- and β-arbutin based on hydrophilic-interaction chromatography. Prior to analysis, interfering compounds that would frequently be present in cosmetics and drugs, particularly biopolymers, were efficiently removed by precipitation with acetonitrile. In this paper, for separation, a Cyclobond I 2000 5 µm 250 × 4.6 mm column was employed as stationary phase and acetonitrile/water 92/8 (v/v) was used as an eluent at a flow rate of 0.8 mL min⁻¹. For quantification, a UV detector operating at 284 nm was applied. Although analysis took less than 10 min, baseline separation of α- and β-arbutin was achieved. The response was highly linear (r > 0.999) and the method had, for both α- and β-arbutin, a LOD of 0.003% (w/w) and a LOQ of 0.009% (w/w). Moreover, the method showed excellent intra-day and inter-day repeatability with relative standard deviations in the range of 0.5% to 2.3% and 1.0% to 2.2%, respectively, with cosmetics, drugs and food supplements as samples.     

Determination of Local Anesthetic Drugs in Human Plasma Using Magnetic Solid-Phase Extraction Coupled with High-Performance Liquid Chromatography

In this work, magnetic tetraethylenepentamine (TEPA)-modified carboxyl–carbon nanotubes were synthesized, characterized, and used as adsorbents to conduct magnetic solid-phase extraction (MSPE) for the preconcentration of seven local anesthetic drugs (procaine, lidocaine, mepivacaine, oxybuprocaine, bupivacaine, tetracaine, and cinchocaine) from human plasma. The separation and determination of analytes were performed on high-performance liquid chromatography with UV detection. Several factors affected the extraction efficiency, such as the amount of adsorbents used, extraction time, sample pH, and optimization of elution conditions. Under optimal conditions, satisfactory linear relationships were obtained in the range of 0.02–5.00 mg/L, with the limits of detection (LOD) ranging from 0.003 mg/L to 0.008 mg/L. The recoveries of analytes for spiked human plasma were in the range of 82.0–108%. Moreover, the precision with intra-day and inter-day RSD values were obtained in the range of 1.5–7.7% and 1.5–8.3%. The results indicated that this method could determine the concentration of seven local anesthetic drugs in human plasma with high precision and repeatability and provide support for the clinical monitoring of the concentration of local anesthetic drugs in human plasma.     

In silico analysis of the pyretic effect of drugs on antimalarial receptors

Malarial infection due to P. falciparum is prominent cause in worldwide fatality. PfCRT, PfDHPS, PfMDR1 and PfDHFR1 play vital role as targets in malarial infection. We chose PfCRT-specific ligands for our study and tested them against all P. falciparum targets. The study was carried out by performing MDS and MD analyses with the NAMD and AutoDock softwares, respectively. The study's goal is to find potential ligands that can act on all malarial targets at various temperatures.The MDS studies revealed structural conformational changes and protein stability from normal human body temperature, 98.6 ​°F, to maximum human body temperature, 107 ​°F. This MDS analysis of Plasmodium targets was carried out by creating a graph of RMSD vs time. Further MD analysis revealed that the ligands reported against PfCRT also had a high binding energy against PfDHPS and PfDHFR. As a result, those ligands can also be targeted for Plasmodium falciparum proteins other than the three mentioned above. These ligands can be subjected to SAR and QSAR studies in order to develop novel molecules for malaria treatment.