Forced degradation study of quinapril by UPLC-DAD and UPLC/MS/MS: Identification of by-products and development of degradation kinetics.

International audienceQuinapril undergoes a significant degradation in the solid state, specially in the presence of humidity, temperature and pharmaceutical excipients. Since dissolution increases the degradation, hydrolytic reactions are among the most common processes involved in drug degradation. Improving the knowledge regarding drug stability, particularly concerning the critical factors that can influence the stability of the active substance in solutions, such as the temperature, the pH and the concentration of catalytic species usually acids or bases are essential for pharmaceutical use. The aim of this study was therefore to develop a new chromatographic method for rapidly and accurately assessing the chemical stability of quinapril and to study the mechanism of quinapril degradation in acidic, neutral and alkaline media at 80°C according to the ICH guidelines. Ultra High Performance Liquid Chromatography (UPLC) coupled with electrospray ionization tandem mass spectrometry and/or diode array detector was used for the rapid and simultaneous analysis of quinapril and its by-products. Separation was achieved using a BEH C18 column and a mixture of acetonitrile-ammonium hydrogencarbonate buffer (pH 8.2; 10 mM) (65:35, v/v) at a flow rate of 0.4 mL/min as a mobile phase. This method allowed drug byproducts profiling, identification, structure elucidation and quantitative determination under stress conditions. The developed method also provides the determination of the kinetic rate constants for the degradation of quinapril and the formation of its major by-products. A complete model including degradation pathway observed under all tested conditions was proposed according to the kinetic study and the structure elucidation of by-products

Seasonal variation of plasma testosterone levels in Algerian male Arabia goats

The aim of the present work was to evaluate the general monthly averages of the testosterone hormone and the influence of  season and photoperiod on plasma testosterone levels in Arabia bucks of Algeria. Testosterone concentrations were determined throughout one year in blood samples collected every fortnight of the month from nine males of Arabia goat breeds, fed a constant diet, maintained without interactions with female goat. Plasma testosterone level was measured by radioimmunoassay. Analyses performed show that the monthly averages of the testosterone hormone vary during the year; higher levels were recorded during August (T=8.57±6.72, P=0.00***) however, bucks displayed the same change tendency during the same period (P=0.79). Plasma testosterone concentrations vary significantly between seasons (P=0.00***) being higher during autumn (6.15±3.81ng/ml) compared with spring (0.90 ± 1.27ng/ml) when hormone synthesis reaches its lowest levels. In conclusion, Arabia bucks of Algeria displayed a clear seasonality of plasma testosterone concentration with very low levels in winter and spring (from January to May) and high levels in summer and autumn (from July to November).Keywords: Arabia bucks, testosterone, season, photoperiod

The Effect of the Stationary Phase on Resolution in the HPLC-Based Separation of Racemic Mixtures Using Vancomycin as a Chiral Selector: A Case Study with Profen Nonsteroidal Anti-Inflammatory Drugs

\ua9 2023 by the authors.Chiral resolution is a technique of choice, making it possible to obtain asymmetric and enantiomerically pure compounds from a racemic mixture. This study investigated the behavior of vancomycin when used as a chiral additive in high-performance liquid chromatography (HPLC) to separate enantiomers of nonsteroidal anti-inflammatory drugs (NSAIDs), including ketoprofen, ibuprofen, flurbiprofen, and naproxen enantiomeric impurities. We compared two achiral stationary phases (C18 and NH2) to assess the impact of mobile phase composition and stationary phase on the vancomycin retention time in the racemic resolution of drug enantiomers. Our results demonstrated the successful enantioseparation of all drugs using vancomycin in the mobile phase (phosphate buffer 0.05 M/2-propanol, 50/50) with an NH2 column. This enhanced separation on the NH2 column resulted from the chromatography system’s efficiency and vancomycin dimers’ stereoselective interaction on the NH2 surface. This study underscores the importance of stationary phase selection in the chiral resolution of NSAIDs with vancomycin as a chiral additive. It offers valuable insights for future research and development of NSAID chiral separation methods, highlighting potential vancomycin applications in this context

Modeling and Optimization of Hybrid Fenton and Ultrasound Process for Crystal Violet Degradation Using AI Techniques

\ua9 2023 by the authors. This study conducts a comprehensive investigation to optimize the degradation of crystal violet (CV) dye using the Fenton process. The main objective is to improve the efficiency of the Fenton process by optimizing various physicochemical factors such as the Fe2+ concentration, H2O2 concentration, and pH of the solution. The results obtained show that the optimal dosages of Fe2+ and H2O2 giving a maximum CV degradation (99%) are 0.2 and 3.13 mM, respectively. The optimal solution pH for CV degradation is 3. The investigation of the type of acid for pH adjustment revealed that sulfuric acid is the most effective one, providing 100% yield, followed by phosphoric acid, hydrochloric acid, and nitric acid. Furthermore, the examination of sulfuric acid concentration shows that an optimal concentration of 0.1 M is the most effective for CV degradation. On the other hand, an increase in the initial concentration of the dye leads to a reduction in the hydroxyl radicals formed (HO•), which negatively impacts CV degradation. A concentration of 10 mg/L of CV gives complete degradation of dye within 30 min following the reaction. Increasing the solution temperature and stirring speed have a negative effect on dye degradation. Moreover, the combination of ultrasound with the Fenton process resulted in a slight enhancement in the CV degradation, with an optimal stirring speed of 300 rpm. Notably, the study incorporates the use of Gaussian process regression (GPR) modeling in conjunction with the Improved Grey Wolf Optimization (IGWO) algorithm to accurately predict the optimal degradation conditions. This research, through its rigorous investigation and advanced modeling techniques, offers invaluable insights and guidelines for optimizing the Fenton process in the context of CV degradation, thereby achieving the twin goals of cost reduction and environmental impact minimization

Efficiency of Hydrogen Peroxide and Fenton Reagent for Polycyclic Aromatic Hydrocarbon Degradation in Contaminated Soil: Insights from Experimental and Predictive Modeling

\ua9 2024 by the authors.This study investigates the degradation kinetics of polycyclic aromatic hydrocarbons (PAHs) in contaminated soil using hydrogen peroxide (H2O2) and the Fenton process (H2O2/Fe2+). The effect of oxidant concentration and the Fenton molar ratio on PAH decomposition efficiency is examined. Results reveal that increasing H2O2 concentration above 25 mmol/samples leads to a slight increase in the rate constants for both first- and second-order reactions. The Fenton process demonstrates higher efficiency in PAH degradation compared to H2O2 alone, achieving decomposition yields ranging from 84.7% to 99.9%. pH evolution during the oxidation process influences PAH degradation, with alkaline conditions favoring lower elimination rates. Fourier-transform infrared (FTIR) spectroscopy analysis indicates significant elimination of PAHs after treatment, with both oxidants showing comparable efficacy in complete hydrocarbon degradation. The mechanisms of PAH degradation by H2O2 and the Fenton process involve hydroxyl radical formation, with the latter exhibiting greater efficiency due to Fe2+ catalysis. Gaussian process regression (GPR) modeling accurately predicts reduced concentration, with optimized ARD-Exponential kernel function demonstrating superior performance. The Improved Grey Wolf Optimizer algorithm facilitates optimization of reaction conditions, yielding a high degree of agreement between experimental and predicted values. A MATLAB 2022b interface is developed for efficient optimization and prediction of C/C0, a critical parameter in PAH degradation studies. This integrated approach offers insights into optimizing the efficiency of oxidant-based PAH remediation techniques, with potential applications in contaminated soil remediation

Formulation and Characterization of Double Emulsions W/O/W Stabilized by Two Natural Polymers with Two Manufacturing Processes (Comparative Study)

\ua9 2024 by the authors.Four distinct types of multiple emulsions were synthesized using xanthan gum and pectin through two distinct manufacturing processes. The assessment encompassed the examination of morphology, stability, and rheological properties for the resulting water-in-oil-in-water (W/O/W) double emulsions. Formulations were meticulously crafted with emulsifiers that were compatible with varying compositions. Remarkably stable multiple emulsions were achieved with a 0.5 wt% xanthan concentration, demonstrating resilience for nearly two months across diverse storage temperatures. In contrast, multiple emulsions formulated with a higher pectin concentration (2.75 wt%) exhibited instability within a mere three days. All multiple emulsions displayed shear-thinning behavior, characterized by a decline in apparent viscosity with escalating shear rates. Comparatively, multiple emulsions incorporating xanthan gum showcased elevated viscosity at low shear rates in contrast to those formulated with pectin. These results underscore the pivotal role of the stepwise process over the direct approach and emphasize the direct correlation between biopolymer concentration and emulsion stability. This present investigation demonstrated the potential use of pectin and xanthan gum as stabilizers of multiple emulsions with potential application in the pharmaceutical industry for the formulation of topical dosage forms

Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses

G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NF\u3baB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5'-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place

Synthesis of novel biocomposite powder for simultaneous removal of hazardous ciprofloxacin and methylene blue: Central composite design, kinetic and isotherm studies using Brouers-Sotolongo family models

Over the past decades, extensive efforts have been made to use biomass-based-materials for wastewater-treatment. The first purpose of this study was to develop and characterize regenerated-reed/reed-charcoal (RR-ChR), an enhanced biosorbent from Tunisian-reed (Phragmites-australis). The second aim was to assess and optimize the RR-ChR use for the removal of binary ciprofloxacin antibiotic (CIP) and methylene blue dye (MB), using Central Composite Design under Response Surface methodology. The third purpose was to explain the mechanisms involved in the biosorption-process. The study revealed that the highest removal-percentages (76.66 % for the CIP and 100 % for the MB) were obtained under optimum conditions: 1.55 g/L of adsorbent, 35 mg/L of CIP, 75 mg/L of MB, a pH of 10.42 and 115.28 min contact time. It showed that the CIP biosorption mechanism was described by Brouers–Sotolongo-fractal model, with regression-coefficient (R2) of 0.9994 and a Person’s Chi-square (X2) of 0.01. The Hill kinetic model better described the MB biosorption (R2 = 1 and X2 = 1.0E-4). The isotherm studies showed that the adsorbent surface was heterogeneous and the best nonlinear-fit was obtained with the Jovanovich (R2 = 0.9711), and Brouers–Sotolongo (R2 = 0.9723) models, for the CIP and MB adsorption, respectively. Finally, the RR-ChR lignocellulosic-biocomposite-powder could be adopted as efficient and cost-effective adsorbent