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Fungi are of considerable importance due to their capacity to biosynthesize various secondary metabolites with bioactive properties that draw high attention in new drug discovery with beneficial uses for improving human well-being and life quality. Aspergillus genus members are widespread and cosmopolitan species with varying economic significance in the fields of industry, medicine, and agriculture. Its species are renowned for their biosynthesis of secondary metabolites, characterized by both potent biological activity and structural novelty, making them a substantial reservoir for the development of new pharmaceuticals. The current work aimed at focusing on one species of this genus, Aspergillus wentii Wehmer, including its reported secondary metabolites in the period from 1951 to November 2023. A total of 97 compounds, including nitro-compounds, terpenoids, anthraquinones, xanthones, benzamides, and glucans. A summary of their bioactivities, as well as their biosynthesis was highlighted. Additionally, the reported applications of this fungus and its enzymes have been discussed. This review offers a useful reference that can direct future research into this fungus and its active metabolites, as well as their possible pharmacological and biotechnological applications. [ABSTRACT FROM AUTHOR]

Solubility is a critical parameter controlling drug absorption after oral administration. For poorly soluble drugs, solubility is influenced by the complex composition of intestinal media and the influence of dosage form excipients, which can cause bioavailability and bioequivalence issues. This study has applied a small scale design of experiment (DoE) equilibrium solubility approach in order to investigate the impact of excipients on fenofibrate solubility in simulated fasted and fed intestinal media. Seven media parameters (bile salt (BS), phospholipid (PL), fatty acid, monoglyceride, cholesterol, pH and BS/PL ratio) were assessed in the DoE and in excipient-free media, and only pH and sodium oleate in the fasted state had a significant impact on fenofibrate solubility. The impact of excipients were studied at two concentrations, and for polyvinylpyrrolidone (PVP, K12 and K29/32) and hydroxypropylmethylcellulose (HPMC, E3 and E50), two grades were studied. Mannitol had no solubility impact in any of the DoE media. PVP significantly increased solubility in a media-, grade- and concentration-dependent manner, with the biggest change in fasted media. HPMC and chitosan significantly reduced solubility in both fasted and fed states in a media-, grade- and concentration-dependent manner. The results indicate that the impact of excipients on fenofibrate solubility is a complex interplay of media composition in combination with their physicochemical properties and concentration. The results indicate that in vitro solubility studies combining the drug of interest, proposed excipients along with suitable simulated intestinal media recipes will provide interesting information with the potential to guide formulation development. [ABSTRACT FROM AUTHOR]

A computationally-assisted and green spectrophotometric method has been developed for the determination of fostemsavir, a recently FDA-approved drug used in combination with antiretroviral drugs to treat multidrug-resistant HIV-1 infection. The method was developed using computational studies and solvent selection based on green chemistry principles. The density functional theory method was employed to identify bromophenol blue as the preferred acid dye for efficient extraction of fostemsavir. The solvent selection process involved a careful evaluation of the green ranking of solvents, which led to the use of water as the solvent. The method involved the extraction of fostemsavir with bromophenol blue to form a yellow ion-pair complex, which exhibited maximally sharp peaks at 418 nm, enabling sensitive visible spectrophotometric determination of fostemsavir in bulk and pharmaceutical preparations. The extraction procedures were optimized, and the method was demonstrated to be sensitive over the concentration range of 2–12 μg/mL fostemsavir. Furthermore, the method was evaluated with respect to green chemistry principles using the analytical eco-scale, the green analytical method index, and analytical greenness metric approach, all of which confirmed that the data obtained by the proposed method were environmentally acceptable. [ABSTRACT FROM AUTHOR]

• Color based friendly analytical method. • Vericiguat is a brand-new, FDA-approved. • Environmentally friendly the presented procedure. • Compatibility with recognized green analytical chemistry. A novel spectrophotometric method aided by computational techniques has been developed to determine vericiguat, a soluble guanylate cyclase stimulator used for reducing the risk of heart failure and cardiovascular mortality. Using density functional theory calculations, 8-hydroxyquinoline was identified as the best coupling agent for the spectrophotometric determination of vericiguat. The method involves the creation of a red-colored chromogen by combining vericiguat with sodium nitrite to form a diazonium ion, which then reacts with 8-hydroxyquinoline. The resulting complex exhibits distinct absorption peaks at 515 nm. Various factors influencing the diazotization process were investigated, and the concentration range of 1–12 μg/mL vericiguat was found to adhere to Beer's law. Job's plot analysis revealed a 1:1 stoichiometric ratio between vericiguat and 8-hydroxyquinoline. This reaction formed the basis for determining vericiguat spectrophotometrically, both in its pure form and in pharmaceutical formulations. Additionally, an analytical greenness metric was employed to evaluate the environmental friendliness of the proposed procedure. The results demonstrated that the method aligns with established values of green analytical chemistry metrics. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sensitive synchronous spectrofluorimetric method for the determination of favipiravir and aspirin in plasma. • ICH M10 validation. • GAPI and AGREE tool greenness evaluation. Favipiravir and aspirin are co-administered during COVID-19 treatment to prevent venous thromboembolism. For the first time, a spectrofluorometric method has been developed for the simultaneous analysis of favipiravir and aspirin in plasma matrix at nano-gram detection limits. The native fluorescence spectra of favipiravir and aspirin in ethanol showed overlapping emission spectra at 423 nm and 403 nm, respectively, after excitation at 368 nm and 298 nm, respectively. Direct simultaneous determination with normal fluorescence spectroscopy was difficult. The use of synchronous fluorescence spectroscopy for analyzing the studied drugs in ethanol at Δλ = 80 nm improved spectral resolution and enabled the determination of favipiravir and aspirin in the plasma matrix at 437 nm and 384 nm, respectively. The method described allowed sensitive determination of favipiravir and aspirin over a concentration range of 10–500 ng/mL and 35–1600 ng/mL, respectively. The described method was validated with respect to the ICH M10 guidelines and successfully applied for the simultaneous determination of the mentioned drugs in pure form and in the spiked plasma matrix. Moreover, the compliance of the method with the concepts of environmentally friendly analytical chemistry was evaluated using two metrics, the Green Analytical Procedure Index and the AGREE tool. The results showed that the described method was consistent with the accepted metrics for green analytical chemistry. [ABSTRACT FROM AUTHOR]

[Display omitted] • FPSE-GC–MS for accurate analysis of pheniramine in postmortem forensic samples. • Proposed method shows great potential in postmortem toxicology sample preparation. • The optimized method was validated according to the SWGTOX guidelines. • Proposed method achieved superior performance to conventional SPE method. • Greenness assessment of the method was achieved using ComplexGAPI and Analytical Eco-Scale. Sample preparation is vital in postmortem toxicology to extract and purify analytes from complex matrices. Challenges like interfering substances and limited sample quantity can be overcome with effective preparation, ensuring accurate results. Hence, a simple, sustainable, affordable, and high-throughput method using fabric phase sorptive extraction (FPSE) - gas chromatography - mass spectrometry (GC–MS) was developed for pheniramine (PHN) analysis in postmortem biological samples (blood and liver). FPSE extraction efficiency was optimized by studying factors like membrane type, stirring time and speed, back-extraction solvent, sample pH, and ionic strength. The optimized method was validated following SWGTOX guidelines for linearity, precision, sensitivity, recovery, matrix effect, stability, and other relevant parameters. The method exhibited linearity in the range of 0.1–10 µg mL−1 for blood and 0.1–10 µg g−1 for liver samples under optimal conditions. The limit of quantification (LOQ) was 0.066 µg mL−1 and 0.073 µg g−1 for PHN in blood and liver, respectively. Intra-day and inter-day precision were < 5.8% and < 9.8%, respectively. Recovery and accuracy ranged from 74 to 80% and 95–100%, respectively. Real autopsy samples were analyzed using this method, compared to conventional solid-phase extraction (SPE), demonstrating its effectiveness. Additionally, the environmental impact and sustainability were assessed using ComplexGAPI and Analytical Eco-Scale tools. The FPSE-GC–MS method showed superior performance, marking a notable advancement in postmortem toxicology sample preparation. To the best of our knowledge, this is the first application of FPSE in the analysis of postmortem tissue samples. In conclusion, FPSE-GC–MS method offers a simple, sustainable, and affordable approach to sample preparation for postmortem forensic samples, overcoming challenges such as interfering substances and limited sample quantity. These advantages of FPSE make it a promising alternative to traditional methods, positions it as a significant advancement in the field, poised to shape the future of sample preparation in forensic toxicology. [ABSTRACT FROM AUTHOR]

The aim of the present research was to develop a magnetic coconut carbon composite (Fe2O3/Fe3O4@CNC) as a solid-phase extraction (SPE) sorbent for the analysis of carcinogenic N-nitrosodimethylamine (NDMA) in pharmaceuticals. Coconut composites modified with Fe2O3 and Fe3O4 were prepared and applied as SPE sorbent for the extraction of NDMA in pharmaceuticals. The sorbent was characterized with X-Ray, infrared spectroscopy and nitrogen porosimetry. The best ions for the Gas Chromatography-Mass Spectrometry with Selected Ion Monitoring (GC-MS/SIM) analysis were m/z 74 and 42 for NDMA, and m/z 80 and 46 for NDMA-d6 internal standard. System has offered great method performance in terms of sensitivity limit of quantitation (LOQ) 16 ng kg−1. The developed sorbent has enhanced the sensitivity and speed of analysis. The developed method was applied to authenticate the presence of NDMA in various pharmaceutical samples. Among the analyzed samples, NDMA impurities were relatively identified at high amounts in nizatidine samples. NDMA was verified in ranitidine, metformin and nizatidine Fe2O3/Fe3O4@CNC composite was used for NDMA identification without pretreatment SPE sorbent enhance sensitivity, reduce analysis time, sustain accuracy & precision High level of NDMA impurity were found in nizatidine pharmaceuticals. [ABSTRACT FROM AUTHOR]

It is widely recognised that drug solubility within the gastrointestinal tract (GIT) differs from values determined in a simple aqueous buffer and to circumvent this problem measurement in biorelevant fluids is determined. Biorelevant fluids are complex mixtures of components (sodium taurocholate, lecithin, sodium phosphate, sodium chloride, pancreatin and sodium oleate) at various concentrations and pH levels to provide systems simulating fasted (FaSSIF) or fed (FeSSIF) intestinal media. Design of Experiment (DoE) studies have been applied to investigate FaSSIF and FeSSIF and indicate that a drug's equilibrium solubility varies over orders of magnitude, is influenced by the drug type and individual or combinations of media components, with some of these interactions being drug specific. Although providing great detail on the drug media interactions these studies are resource intensive requiring up to ninety individual experiments for FeSSIF. In this paper a low sample number or reduced DoE system has been investigated by restricting components with minimal solubility impact to a single value and only investigating variations in the concentrations of sodium taurocholate, lecithin, sodium oleate, pH and additionally in the case of fed media, monoglyceride. This reduces the experiments required to ten (FaSSIF) and nine (FeSSIF). Twelve poorly soluble drugs (Ibuprofen, Valsartan, Zafirlukast, Indomethacin, Fenofibrate, Felodipine, Probucol, Tadalafil, Carvedilol, Aprepitant, Bromocriptine and Itraconazole) were investigated and the results compared to published DoE studies and literature solubility values in human intestinal fluid (HIF), FaSSIF or FeSSIF. The solubility range determined by the reduced DoE is statistically equivalent to the larger scale published DoE results in over eighty five percent of the cases. The reduced DoE range also covers HIF, FaSSIF or FeSSIF literature solubility values. In addition the reduced DoE provides lowest measured solubility values that agree with the published DoE values in ninety percent of the cases. However, the reduced DoE only identified single and in some cases none of the major components influencing solubility in contrast to the larger published DoE studies which identified multiple individual components and component interactions. The identification of significant components within the reduced DoE was also dependent upon the drug and system under investigation. The study demonstrates that the lower experimental number reduces statistical power of the DoE to resolve the impact of media components on solubility. However, in a situation where only the solubility range is required the reduced DoE can provide the desired information, which will be of benefit during in vitro development studies. Further refinements are possible to extend the reduced DoE protocol to improve biorelevance and application into areas such as PBPK modelling. [ABSTRACT FROM AUTHOR]