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The preparation of titania-based photocatalysts has been largely investigated in the literature. Nevertheless, the study of the influence of different solvents in the synthesis mixture requires further analysis. Addressing this issue, we explored the potential of heterogeneous photocatalysis with nano-sized titanium dioxide (TiO2) synthesized via the sol–gel method with and without ultrasound for the degradation of sulfamethoxazole (SMX) in water. Specifically, we engineered TiO2 nanoparticles within the 20–30 nm range, in order to work in the same particle size range of Evonik P25. The synthesis was conducted in five distinct solvents, n-hexane, decane, isopropanol, ethanol, and 1-octanol, and it was evaluated with the presence and absence of ultrasound. Following synthesis, the powders were thoroughly characterized. When nonpolar solvents were used, the photocatalysts were characterized by the presence of both anatase and brookite phases, while with polar solvents, the only polymorph present was anatase. A different behavior was shown by 1-octanol, where the role of the solvent was so important that US did not affect the final sample features. The samples prepared in ethanol and isopropanol exhibited superior activity compared to those synthesized in other solvents in the SMX photodegradation (about 35% after 6 h), and the effect of US during preparation resulted positive for all solvents (an average increase of SMX photodegradation in the range of 5–10% for the different photocatalysts for each degradation time). [ABSTRACT FROM AUTHOR]

In recent years, due to the high consumption of drugs both for human needs and for their growing use, especially as regards antibiotics, in the diet of livestock, water pollution has reached very high levels and attracted widespread attention. Drugs have a stable chemical structure and are recalcitrant to many treatments, especially biological ones. Among the methods that have shown high efficiency are advanced oxidation processes (AOPs) which are, among other things, inexpensive and eco-friendly. AOPs are based on the production of reactive oxygen species (ROS) able to degrade organic pollutants in wastewater. The main problem related to the degradation of drugs is their partial oxidation to compounds that are often more harmful than their precursors. In this review, which is not intended to be exhaustive, we provide an overview of recent advances in the removal of organic drugs via advanced oxidation processes (AOPs). The salient points of each process, highlighting advantages and disadvantages, have been summarized. In particular, the use of AOPs such as UV, ozone, Fenton-based AOPs and heterogeneous photocatalysis in the removal of some of the most common drugs (tetracycline, ibuprofen, oxytetracycline, lincomycin) has been reported. [ABSTRACT FROM AUTHOR]

This study describes the synthesis of an innovative nanomaterial (patent application number BR 1020210000317) composed of cobalt ferrite functionalized in niobium pentoxide CoFe2O4@Nb5O2 (CFNb), synthesized via green synthesis using tangerine peel extract. The material emphasizes the combination of a magnetic material (which allows for easy recovery after application) with niobium pentoxide (a metal which is abundant in Brazil). CFNb was applied as a catalyst for the paracetamol (PCT) degradation by photocatalysis. The new materials were characterized through surface and pore analysis (SBET, SEXT, Smic, Vmic, and VTOTAL), photoacoustic spectroscopy (PAS), zero charge point (pHPZC, scanning electron microscopy (SEM/EDS), and X-ray diffraction (XRD). The reaction parameters studied included pH and catalyst concentration. The results indicated that the CFNb nanocatalysts were efficient in the paracetamol degradation, presenting better results in conditions of low pH (close to 2) and low catalyst concentration under irradiation of the 250 W mercury vapor lamp (greater than 28 mW·cm−2) at 60 min of reaction. [ABSTRACT FROM AUTHOR]

The stability of active pharmaceutical ingredients (APIs) and the corresponding pharmaceutical formulations are nowadays of great importance in pharmaceutical research and technology. The quality of an API or of finished pharmaceutical products (FPPs) is time dependent under the influence of several parameters, such as light and air exposure, temperature, and humidity. Additionally, the stability profile of an API is influenced by the formulation composition, due to the presence of excipients or by the characteristic of the packaging materials. In this sense, the main objective of this study was to analyze the degradation kinetics of the antihypertensive drug moxonidine as a pure ingredient (MOX) and in two different solid mixtures, one corresponding to a pharmaceutical formulation (MOXTAB) and the other to an enriched pharmaceutical formulation in MOX (MOXMIX). As investigation techniques, FTIR (Fourier transform infrared) spectroscopy and TG/DTG/HF analysis were employed, while the thermoanalytical data were processed according to the ASTM E698 kinetic method and the isoconversional methods of Flynn–Wall–Ozawa (FWO) and Friedman (FR). The kinetic methods revealed that the excipients have a stabilizing effect on MOX (in terms of Ea values), but the decomposition mechanism of the samples is complex, according to the results suggested by the analysis of Ea vs. α values. [ABSTRACT FROM AUTHOR]

In this study, three CuFe-MOFs were successfully synthesized by a solvothermal process by changing the ratio of solvents, salts, or temperature. These MOFs named CuFe(BDC-NH2)R, CuFe(BDC-NH2)S, and CuFe(BDC-NH2)D showed rod-shaped, spindle-like, and diamond-like structures, respectively. The CuFe(BDC-NH2)D and CuFe(BDC-NH2)S were found to exhibit an improved PMS activation for Rhodamine B removal attaining levels around 92%. Their effective removal capability was investigated as a function of the pH, catalyst dosage, and the effect of the application of UV radiation. The best degradation system was photo-assisted activation of PMS when CuFe(BDC-NH2)D and CuFe(BDC-NH2)S were used. Under these conditions, the degradation of a mixture of antibiotic and anti-inflammatory drugs (sulfamethoxazole and antipyrine) was evaluated with the results revealing the total degradation of both drugs after 1 h. A higher antibacterial activity was attained with the system CuFe(BDC-NH2)R/PMS due to the high copper content with respect to the others. [ABSTRACT FROM AUTHOR]

The formation of N-nitrosodimethylamine (NDMA) in ranitidine hydrochloride drug substance (DS) and drug products has attracted considerable attention over the last few years. The drug structure is unusual in that it contains a vinyl nitro moiety. Although a variety of studies have been carried out to understand how NDMA is formed in the DS solids, a mechanistic description of NDMA formation has remained elusive. A new mechanistic view of NDMA formation is detailed here. Autoxidation of ranitidine can rationalize nitrite ion and dimethylamine liberation from ranitidine. The subsequent nitrosation is argued to be due to conversion of nitrite ion to the gas phase nitrosating agent nitrosyl chloride, NOCl. Oxygen scavenging packaging systems should be able to stop the autoxidation, and thus shut down the nitrite release from ranitidine. Without nitrite release NDMA cannot form. This may provide a practical means to stabilize ranitidine DS and solid dosage formulations against NDMA formation. [ABSTRACT FROM AUTHOR]

• The carbon fiber amperometric methodology is suitable for monitoring NOR degradation. • Analytical sensitivity allows NOR to be quantified during electrolytic degradation. • The CF sensor is not affected by the byproducts of drug electrodegradation. • The method is promising for monitoring the treatment of NOR-contaminated water. In this work, an amperometric analysis strategy using a carbon fiber (CF) rod as an anode was developed to follow the degradation process of the norfloxacin (NOR) molecule via electrochemical advanced oxidation processes (EAOP). The voltammetric study showed that drug oxidation is an irreversible process which involves, in the determining stage of the reaction, a proton and an electron in an EC (electron transfer followed by chemical reaction) mechanism. After optimizing the electroanalytical conditions, CF sensor showed a linear amperometric response at concentrations ranging from 1.6 μmol L−1 to 30.0 μmol L−1, with detection and quantification limits of 0.5 μmol L−1 and 1.8 μmol L−1, respectively, which are sufficient to enable in monitoring the drug during its electrolytic degradation. The results clearly showed that the by-products generated during drug degradation do not interfere with the current signal. Other application scenarios were evaluated, such as the determination of NOR in river waters and in the presence of different drug degradation by-products, obtained after EAOPs in chloride-containing medium, and no interference was observed during the electroanalysis. Therefore, the proposed analytical methodology is promising for monitoring and controlling the treatment of water contaminated with NOR antibiotic. [ABSTRACT FROM AUTHOR]

This study describes the synthesis of an innovative nanomaterial (patent application number BR 1020210000317) composed of cobalt ferrite functionalized in niobium pentoxide CoFe2O4@Nb5O2 (CFNb), synthesized via green synthesis using tangerine peel extract. The material emphasizes the combination of a magnetic material (which allows for easy recovery after application) with niobium pentoxide (a metal which is abundant in Brazil). CFNb was applied as a catalyst for the paracetamol (PCT) degradation by photocatalysis. The new materials were characterized through surface and pore analysis (SBET, SEXT, Smic, Vmic, and VTOTAL), photoacoustic spectroscopy (PAS), zero charge point (pHPZC, scanning electron microscopy (SEM/EDS), and X-ray diffraction (XRD). The reaction parameters studied included pH and catalyst concentration. The results indicated that the CFNb nanocatalysts were efficient in the paracetamol degradation, presenting better results in conditions of low pH (close to 2) and low catalyst concentration under irradiation of the 250 W mercury vapor lamp (greater than 28 mW·cm−2) at 60 min of reaction.

TiO2 is one of the most used materials in the photocatalysis of organic pollutants. It can be prepared by different techniques including electrochemical methods. The influence of the structure of TiO2 films grown electrochemically using plasma electrolytic oxidation (PEO) was investigated in terms of the photocatalytic activity. The film microstructure and morphology were analyzed and its influence in photocatalytic response was evaluated by photodegradation of ciprofloxacin (CIP). A strong influence of the synthesis temperature on the structural properties (pore diameter and crystallite size) was observed, which could be correlated with the photocatalytic activity change of the synthesized materials. To correlate the structural to the photocatalytic activity, besides Pareto graphs and analysis, a variable called microstructure ratio-SR (pore diameter/crystallite size) was evaluated. Results have shown the F2020005 film (20 mA cm−2, 20 °C and 0.05 mol L−1) presented the highest photocatalytic activity. As a complementary study, ecotoxicity tests were realized using Lactuca sativa L. seeds and the macrophyte Lemna minor. In these experiments, it was observed that the effluents of the photocatalysis carried out with the materials synthesized by PEO presented lower toxicity, compared to the CIP solution without any treatment. The best results for the degradation of CIP were obtained using films synthesized at higher temperatures. CIP photocatalytic degradation using TiO2 films grown by PEO was effective, generating byproducts of low toxicity. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel TiO 2 @CuFe 2 O 4 /Ag nano-dandelion magnetic composites were synthesized by hydrothermal and sol–gel method. • CuFe 2 O 4 and Ag improved light absorption and electron charge transfer of composites. • The composites exhibited good photocatalytic activity for degradation of Naproxen and Rhodamine B above 90% • Type II heterojunction mechanism was proposed by performing radical scavenger experiments. • The reusability and recyclability of the photocatalyst and reaction kinetics were investigated. Nano-dandelion TiO 2 and magnetic CuFe 2 O 4 were synthesized with hydrothermal and sol–gel processes, respectively. A series of composites containing different amounts of CuFe 2 O 4 and Ag were also prepared using a photoreduction method. The composites were subsequently used for photodegradation of Naproxen and Rhodamine B under UV–Vis light irradiation. The synthesized photocatalysts were characterized by XRD, FTIR, FESEM, EDX, TEM, BET-BJH, DRS, and PL analyses. XRD and FESEM results confirmed the successful synthesis of the dandelion structure for the composites. The VSM analysis also demonstrated the enhancement of magnetic properties of composites. DRS results indicated that CuFe 2 O 4 loading and Ag doping resulted in a decrease in the band gap energy and enhanced absorption of light in the visible region as compared with pure TiO 2. The presence of CuFe 2 O 4 and Ag also increased charge transfer by decreasing electron-hole recombination rates by creating a Schottky-barrier interface which was indicated by the PL spectra. The composite containing 20% CuFe 2 O 4 and 3% Ag (designated as TC20-3Ag) showed better performance as compared with other photocatalysts for photodegradation of Naproxen (92.56%) and Rhodamine B (91.16%) over a 150-minute reaction time. The sample also exhibited good stability after 5 cycles. The effects of operating parameters such as the pH of the solution, the photocatalyst dosage, and initial pollutant concentration were also investigated. It was found that a pseudo-first-order model adequately described the photodegradation kinetics. The results indicated that superoxide and holes were reactive species, and a possible mechanism for the photodegradation of Naproxen by TC20-3Ag was suggested. [ABSTRACT FROM AUTHOR]

One of the most common functional groups encountered in drug molecules is the amide, and the most common degradation pathway for amides is base-mediated hydrolysis to its constituent amine and carboxylic acid. Herein, we report for the first time, a base-mediated oxidative degradation pathway of secondary amides to primary amides. This transformation also represents a novel synthetic methodology, reported for the first time in this work, in transforming secondary amides to primary amides without using any oxidative reagents. The introduction of this mechanism into the pharmaceutical literature is important given that the mechanism and required reactants are present to carry out the chemistry in dosage forms. [ABSTRACT FROM AUTHOR]

Stability studies performed by the pharmaceutical industry are principally designed to fulfill licensing requirements. Thus, post-dilution or post-reconstitution stability data are frequently limited to 24 h only for bacteriological reasons, regardless of the true physicochemical stability which could, in many cases, be longer. In practice, the pharmacy-based centralized preparation may require preparation in advance for administration, for example, on weekends, holidays, or in general when pharmacies may be closed. We report an innovative strategy for storing resuspended solutions of azacitidine, a well-known chemotherapic agent, for which the manufacturer lists maximum stability of 22 h. By placing the syringe with the azacitidine reconstituted suspension between two refrigerant gel packs and storing it at 4 °C, we found that the concentration of azacitidine remained above 98% of the initial concentration for 48 h, and no change in color nor the physicochemical properties of the suspension were observed throughout the study period. The physicochemical and microbiological properties were evaluated by HPLC–UV and UHPLC-HRMS analysis, FTIR spectroscopy, pH determination, visual and subvisual examination, and sterility assay. The HPLC-UV method used for evaluating the chemical stability of azacitidine was validated according to ICH. Precise control of storage temperature was obtained by a digital data logger. Our study indicates that by changing the storage procedure of azacitidine reconstituted suspension, the usage window of the drug can be significantly extended to a time frame that better copes with its use in the clinical environment.

A thorough analysis about iron speciation in the direct Fe-SBA-15 synthesis by using metal precursors with distinct counter-ions: (NO3)−, (SO4)2−, Cl− and (C5H7O2)− is presented. Long-range hexagonal ordering and high specific areas were achieved for all of silicates. Although a Si/Fe molar ratio of 20 allowed incorporating a similar metal content in the materials, several iron species were formed as a function of metal source. The solids were tested as Fenton catalysts for the paracetamol degradation and the importance of the different developed metal species on the catalytic efficiency could be corroborated. The presence of sulfate groups in the synthesis gel led to more active catalysts. Here, isolated Fe3+ ions, stabilized on the structure by multiple oxygen bridge bonds, could interact more efficiently with H2O2 to generate OH· oxidative species for the degradation of organic molecules. Finally, it was demonstrated that by means of sol–gel method and pH conditions control, it is possible handling the metal precursor to achieve certain chemical species on the surface with a higher catalytic efficiency for Fenton process. [ABSTRACT FROM AUTHOR]

Abstract The ability to produce and isolate relatively pure amounts of relevant degradation products is key to several aspects of drug product development: (a) aid in the unambiguous structural identification of such degradation products, fulfilling regulatory requirements to develop safe formulations (International Conference on Harmonization Q3B and M7); (b) pursue as appropriate safety evaluations with such material, such as chronic toxicology or Ames testing; (c) for a specified degradation product in a late-stage regulatory filing, use pure and well-characterized material as the analytical standard. Producing such materials is often a resource- and time-intensive activity, either relying on the isolation of slowly formed degradation products from stressed drug product or by re-purposing the drug substance synthetic route. This problem is exacerbated if the material of interest is an oxidative degradation product, because typical oxidative stressing (H 2 O 2 and radical initiators) tends to produce a myriad of irrelevant species beyond a certain stress threshold, greatly complicating attempts for isolating the relevant degradation product. In this article, we present reagents and methods that may allow the rapid and selective enrichment of active pharmaceutical ingredient with the desired oxidative degradation product, which can then be isolated and used for purposes described above. [ABSTRACT FROM AUTHOR]

[Display omitted] • Orange peel was utilized for synthesis of TM doped ZnO nanoparticles. • TM doping affected the charge separation of carriers. • Ni doped ZnO nanoparticles exhibited the maximum photocatalytic degradation efficiency. • The synthesized catalysts are highly stable and can be reused for 5 cycles. The present work investigates the degradation of Amoxicillin using ZnO and Fe, Ni, Co doped ZnO nanoparticles synthesized using orange peel extract. The synthesized catalysts were characterised with the help of X-ray diffraction, scanning electron microscopy, UV–Visible and photoluminescence spectroscopy for structural and optical properties and the study of charge transport behaviour of the catalysts. The observed results indicate that the Ni doped ZnO nanoparticles exhibit superior degradation efficiencies of 80.71% and 86.21% under UV light and UV + visible light irradiation. Moreover, the slightly basic environment was found to be favourable for optimizing the degradation efficiency of the catalyst, as confirmed by the pH variation experiment. The scavenging experiments were utilized to reveal the most prominent role of hydroxyl radicals in the degradation of Amoxicillin. Additionally, a mere 10.97% reduction in degradation efficiency was observed after fours cycles of degradation experiment. The plausible pathway of amoxicillin degradation has been included into this study as well. Hence, the transition metal (TM) doped ZnO nanoparticles synthesized through waste orange peels suggest their utilization as efficient photo catalyst in Amoxicillin degradation. [ABSTRACT FROM AUTHOR]

Stress factors caused by inadequate storage can induce the unwanted degradation of active compounds in pharmaceutical formulations. Resonance Raman spectroscopy is presented as an analytical tool for rapid monitoring of small concentration changes of tetracycline and the metabolite 4˗epianhydrotetracycline. These degradation processes were experimentally induced by changes in temperature, humidity, and irradiation with visible light over a time period of up to 23 days. The excitation wavelength λexc = 413 nm was proven to provide short acquisition times for the simultaneous Raman spectroscopic detection of the degradation of tetracycline and production of its impurity in small sample volumes. Small concentration changes could be detected (down to 1.4% for tetracycline and 0.3% for 4-epianhydrotetracycline), which shows the potential of resonance Raman spectroscopy for analyzing the decomposition of pharmaceutical products.

Cystinosis is an orphan disease caused by a genetic mutation that leads to deposition of cystine crystals in many organs including cornea. Ophthalmic manifestation of the disease can be treated with hourly instillation of cysteamine eye drops. The hourly eye drop instillation is tedious to the patients leading to poor compliance and additionally, significant degradation of the drug occurs within one week of opening the bottle, which further complicates this delivery approach. This paper focuses on designing a contact lens to treat the disease with improved efficacy compared to eye drops, and also exploring safety of the drug eluding contact lens in an animal model. Our goal is to design a lens that is safe and that can deliver a daily therapeutic dose of cysteamine to the cornea while retaining drug stability. We show that cysteamine diffuses out rapidly from all lenses due to its small size. Vitamin E incorporation increases the release duration of both ACUVUE ® OASYS ® and ACUVUE ® TruEye TM but the effect is more pronounced in TruEye TM likely due to the low solubility of vitamin E in the lens matrix and higher aspect ratio of the barriers. The barriers are not effective in hydrogel lenses, which along with the high aspect ratio in silicone hydrogels suggests that barriers could be forming at the interface of the silicone and hydrogel phases. The presence of vitamin E has an additional beneficial effect of reduction in the oxidation rates, likely due to a transport barrier between the oxygen diffusing through the silicone channels and drug located in the hydrogel phase. Based on this study, both Acuvue ® OASYS ® and ACUVUE ® TruEye TM can be loaded with vitamin E to design a cysteamine eluting contact lenses for effective therapy of cystinosis. The lenses must be worn for about 4–5 hr. each day, which is less than the typical duration of daily-wear. The vitamin E and cysteamine loaded lenses did not exhibit any toxicity in a rabbit model over a period of 7-days. [ABSTRACT FROM AUTHOR]

Pharmaceutical drugs are available to astronauts to help them overcome the deleterious effects of weightlessness, sickness and injuries. Unfortunately, recent studies have shown that some of the drugs currently used may degrade more rapidly in space, losing their potency before their expiration dates. To complicate matters, the degradation products of some drugs can be toxic. Here, we present a preliminary investigation of the ability of Raman spectroscopy to quantify mixtures of four drugs; acetaminophen, azithromycin, epinephrine, and lidocaine, with their primary degradation products. The Raman spectra for the mixtures were replicated by adding the pure spectra of the drug and its degradant to determine the relative percent contributions using classical least squares. This multivariate approach allowed determining concentrations in ~10 min with a limit of detection of ~4% of the degradant. These results suggest that a Raman analyzer could be used to assess drug potency, nondestructively, at the time of use to ensure crewmember safety.

An in-depth analysis of nanotechnology applications for the improvement of solubility, distribution, bioavailability and stability of reverse transcriptase inhibitors is reported. Current clinically used nucleoside and non-nucleoside agents, included in combination therapies, were examined in the present survey, as drugs belonging to these classes are the major component of highly active antiretroviral treatments. The inclusion of such agents into supramolecular vesicular systems, such as liposomes, niosomes and lipid solid NPs, overcomes several drawbacks related to the action of these drugs, including drug instability and unfavorable pharmacokinetics. Overall results reported in the literature show that the performances of these drugs could be significantly improved by inclusion into nanosystems.

Rigosertib is a novel anticancer drug in clinical development by Onconova therapeutics, Inc. Currently, it is in pivotal phase III clinical trials for myelodysplastic syndrome (MDS) patients. Chemically, it is a sodium salt of weak acid with low solubility in lower pH solutions. In the preliminary studies, it was found that rigosertib is unstable in acidic conditions and forms multiple degradation products. In this research, drug degradation kinetics of rigosertib were studied in acidic conditions. Rigosertib follows pseudo-first-order general acid catalysis reaction. Cholestyramine, which is a strong anion exchange resin, was used to form complex with drug to improve stability and dissolution in acidic conditions. Drug complex with cholestyramine showed better dissolution profile compared to drug alone. Effect of polyethylene glycol was investigated on the release of drug from the drug resin complex. Polyethylene glycol further improved dissolution profile by improving drug solubility in acidic medium. [ABSTRACT FROM AUTHOR]

Cyclodextrins (CDs) are enabling pharmaceutical excipients that can enhance both solubility and stability of wide variety of drugs in aqueous solutions through formation of drug/CD inclusion complexes where apolar moieties of the drug molecules are located inside the CD cavity. In properly designed pharmaceutical formulations CDs will improve physiochemical properties of lipophilic drugs without affecting their intrinsic ability to permeate biological membranes. Here the effect of CD complexes on the chemical stability of drugs is reviewed. Numerous studies shown that in aqueous solutions CD complexation can hamper hydrolysis, oxidation, photodegradation, isomerization and enzyme catalyzed degradation of dissolved drugs. However, some drugs, such as β-lactam antibiotics, can under certain conditions undergo CD catalyzed degradation in aqueous solutions. Also, some drugs that are stabilized by CDs in aqueous solutions are destabilized by the same CDs in solid dosage forms. Thus, the effects of CDs on drug stability have to be tested and verified in the final drug formulation and under the recommended storage conditions. [ABSTRACT FROM AUTHOR]

Antimicrobial drugs are used to treat pathogenic bacterial infections in animals and humans. The by-stander enteric bacteria of the treated host's intestine can become exposed to the drug or its metabolites reaching the intestine in antimicrobially active form. We consider which processes and variables need to be accounted for to project the antimicrobial concentrations in the host's intestine. Those include: the drug's fraction (inclusive of any active metabolites) excreted in bile; the drug's fractions and intestinal segments of excretion via other mechanisms; the rates and intestinal segments of the drug's absorption and re-absorption; the rates and intestinal segments of the drug's abiotic and biotic degradation in the intestine; the digesta passage time through the intestinal segments; the rates, mechanisms, and reversibility of the drug's sorption to the digesta and enteric microbiome; and the volume of luminal contents in the intestinal segments. For certain antimicrobials, the antimicrobial activity can further depend on the aeration and chemical conditions in the intestine. Model forms that incorporate the inter-individual variation in those relevant variables can support projections of the intestinal antimicrobial concentrations in populations of treated host, such as food animals. To illustrate the proposed modeling framework, we develop two examples of treatments of bovine respiratory disease in beef steers by oral chlortetracycline and injectable third-generation cephalosporin ceftiofur. The host's diet influences the digesta passage time, volume, and digesta and microbiome composition, and may influence the antimicrobial loss due to degradation and sorption in the intestine. We consider two diet compositions in the illustrative simulations. The examples highlight the extent of current ignorance and need for empirical data on the variables influencing the selective pressures imposed by antimicrobial treatments on the host's intestinal bacteria. [ABSTRACT FROM PUBLISHER]

Metal ions play an important role in oxidative drug degradation. One of the most ubiquitous metal ion impurities in excipients and buffers is Fe(III). In the field of oxidative drug degradation chemistry, the role of Fe(III) has been primarily discussed in terms of its effect in reaction with trace hydroperoxide impurities. However, the role of Fe(III) acting as a direct oxidant of drug molecules, which could operate in the absence of any hydroperoxide impurities, is less common. This work focuses on Fe(III)-induced oxidation of some aromatic drug molecules/drug fragments containing benzylic C-H bonds in the absence of initiating peroxides. Alcohol and ketone degradates are formed at the benzylic carbon atom. The formation of a π-stabilized cation radical is postulated as the key intermediate for the downstream oxidation. Implications are briefly discussed. [ABSTRACT FROM AUTHOR]

Contaminants of emerging concern (CECs), including pharmaceuticals, are frequently detected at low concentrations in natural water and can cause adverse effect in biota, such as antibiotic resistance. Therefore, it is important to reduce their introduction in the environment by increasing their removal efficiency from wastewaters. In this work, a new photocatalytic method for removal of three CECs target molecules (i.e. atenolol, levofloxacin, trimethoprim) from water is proposed. The photoactive species is decatungstate anion both in solution and immobilized on modified silica particles. The degradation process is studied at ambient temperature, atmospheric pressure and at pH values similar to that of natural waters. EPR spin trapping technique and HPLC–MS analysis give evidence that degradation is mediated by OH radicals. The heterogeneous catalyst is stable and can be recycled without a significant loss of efficiency thus opening the possibility of developing new solid materials with interesting photocatalytic performance. [ABSTRACT FROM AUTHOR]

Drug biotransformation by the host microbiome can impact the therapeutic success of treatment. In the context of cancer, drug degradation can take place within the microenvironment of the targeted tumor by intratumor bacteria. In pancreatic cancer, increased chemo-resistance against the frontline chemotherapy gemcitabine is thought to arise from drug degradation by the tumor microbiome. This bacterial-drug interaction highlights the need for developing rapid assays for monitoring bacterial gemcitabine breakdown. While chemical approaches such as high-performance liquid chromatography are suitable for this task, they require specialized equipment and expertise and are limited in throughput. Functional cell-based assays represent an alternate approach for performing this task. We developed a functional assay to monitor the rate of bacterial gemcitabine breakdown using a highly sensitive bacterial reporter strain. Our method relies on standard laboratory equipment and can be implemented at high throughput to monitor drug breakdown by hundreds of strains simultaneously. This functional assay can be readily adapted to monitor degradation of other drugs. Key features Quantification of gemcitabine breakdown by incubating bacteria that degrades the drug and subsequently testing the growth of a reporter strain on filtered supernatant. Use of an optimized reporter strain that was genetically engineered to be a non-degrader strain and highly sensitive to gemcitabine. A high-throughput assay performed in microplates that can be adjusted for identifying bacteria with a fast or slow gemcitabine degradation rate. The assay results can be compared to results from a standard curve with known drug concentrations to quantify degradation rate., Competing Interests: Competing interestsThe authors declare no conflicts of interest or competing interests., (©Copyright : © 2023 The Authors; This is an open access article under the CC BY-4.0 license.)

Argatroban (ARGA), used as intravenous anticoagulant drug, has been reported to photodegrade under light exposure, requiring specific precautions at handling, storage and administration. Thus, for the first time, aqueous ARGA photodegradation under aerobic conditions has been described in terms of photoproducts, phototransformation processes and potential implications. ARGA significant photoproducts were successfully separated and characterized by gradient reversed-phase liquid chromatography coupled with high-resolution multistage mass spectrometry (LC/HR–MS n ). Hitherto still not available in literature, ARGA in-depth fragmentation study was conducted so as to thoroughly sort out the main mechanisms specific to the molecule and therefore, to propose a fragmentation pattern relevant to the identification of ARGA related substances. Thereafter, in view of the structural characteristics of the photoproducts formed, ARGA photodegradation pathways could be worked out, showing that whether by direct photolysis or through photosensitization, the methyltetrahydroquinoline nitrogen and that of guanidine group would be mainly involved in photolysis initiation reactions, through one-electron oxidation along with proton loss. Desulfonation, cyclisation affording compounds of diazinane type, and/or rearrangements with transfer of the methyltetrahydroquinoline group toward the guanidine function were observed accordingly. Having a good insight into ARGA photodegradation pathways allows for consistent measures in view of mitigating or avoiding the drug decay and the related potential effects. [ABSTRACT FROM AUTHOR]

For pharmacokinetic/pharmacodynamic (PK/PD) assessment of antibiotics combinations in in vitro infection models, accurate and precise quantification of drug concentrations in bacterial growth medium is crucial for derivation of valid PK/PD relationships. We aimed to (i) develop a high-performance liquid chromatography (HPLC) assay to simultaneously quantify linezolid (LZD), vancomycin (VAN) and meropenem (MER), as typical components of broad-spectrum antibiotic combination therapy, in bacterial growth medium cation-adjusted Mueller-Hinton broth (CaMHB) and (ii) determine the stability profiles of LZD, VAN and MER under conditions in in vitro infection models. To separate sample matrix components, the final method comprised the pretreatment of 100 μL sample with 400 μL methanol, the evaporation of supernatant and its reconstitution in water. A low sample volume of 2 μL processed sample was injected onto an Accucore C-18 column (2.6 μm, 100 × 2.1 mm) coupled to a Dionex Ultimate 3000 HPLC+ system. UV detection at 251, 240 and 302 nm allowed quantification limits of 0.5, 2 and 0.5 μg/mL for LZD, VAN and MER, respectively. The assay was successfully validated according to the relevant EMA guideline. The rapid method (14 min) was successfully applied to quantify significant degradation of LZD, VAN and MER in in vitro infection models: LZD was stable, VAN degraded to 90.6% and MER to 62.9% within 24 h compared to t = 0 in CaMHB at 37 °C, which should be considered when deriving PK/PD relationships in in vitro infection models. Inclusion of further antibiotics into the flexible gradient-based HPLC assay seems promising. [ABSTRACT FROM AUTHOR]

INTRODUCTION: in spite of significant risks, as well as non-clinical importance due to loss of potency, stiff penalties against administration of expired medications are still not appropriately enforced by health policy makers in many developing countries, possibly because of little evidence to support that expired medications are hazardous. The purpose of this study therefore, was to investigate the effect of expiration dates on in vitro bacteriostatic potentials of oral paediatric antibiotics. METHODS: comparative bacteriostatic potentials of 31 expired and seven corresponding unexpired oral paediatric antibiotics were determined on infantile diarrhoeagenic bacteria, using a modification of agar well-diffusion method. RESULTS: verall total percentage in vitro resistance rates against expired and unexpired paediatric antibiotics respectively were - E. coli (d"100% vs. d"15.9%), Klebsiella pneumoniae (d"100% vs. d"31.3%), Proteus mirabilis (d"91.7% vs. d"41.7%) and Staphylococcus aureus (d"100% vs. d"18.2%). Resistance rates of 45.5-55.8% (sulfamethoxazole + trimethoprim 5), 39.5-63.6% (amoxycillin 6), 46.5-54.5% (cotrimoxazole 7), 37.5-63.6% (ampicillin + cloxacillin 18), and higher resistance rates of e"75.0-100% were exhibited towards remaining expired antibiotics. Higher total resistance and multiple antibiotic resistance (MAR) rates were also recorded against expired antibiotics (45.2-93.5%) compared to unexpired antibiotics (28.6-57.2%), except for few strains of E. coli and Proteus mirabilis. Furthermore, unexpired paediatric antibiotics exhibited wider zones of inhibition towards the test diarrhoeagenic bacteria (e"25.0 mm diameter). CONCLUSION: this study provided preliminary microbiological results on the appreciable reduction in in vitro bacteriostatic potentials, as well as higher resistance and multiple antibiotic resistance rates among expired oral paediatric antibiotics on infantile diarrhoeagenic bacteria. Apart from less-efficacy, administration of expired antibiotics can lead to increased antibiotic resistance and clinical treatment failure, as well as adverse drug reactions.