Future Journal of Pharmaceutical Sciences最新文献

Background

Fentanyl is a highly potent analgesic, used in surgery, frequently abused or used in drug-facilitated crimes (DFC) and in military activities. It is also increasingly used in the treatment of chronic pain (especially in cancer patients). The improper use of transdermal patch forms can cause toxicity and deaths, related to overdose or combined use with other drug substances. Methods are needed for fast, reliable and inexpensive fentanyl detection and we aimed to develop such a method in urine using LC–MS/MS, especially for toxic and fatal concentrations which lack in the literature.

Results

An LC–MS/MS method has been presented for the co-determination of fentanyl and its main metabolite, norfentanyl in urine. The recoveries of the extraction method were 95(± 6)% and 70(± 9)% for fentanyl and norfentanyl, respectively. LOD and LOQ values are 1.7 and 14.0 ng/mL for fentanyl, while they were 20.6 ng/mL and 42.0 ng/mL for norfentanyl.

Conclusion

A rapid, sensitive, very practical, inexpensive and a high-recovery analysis method is developed and validated. This is the only fentanyl monitoring LC–MS/MS method in urine having a linearity over a wide range up to 500.0 ng/mL and its success is demonstrated on real samples in the therapeutic drug monitoring of fentanyl and is expected to contribute to clarify intoxications/deaths related to its use.

Graphical Abstract

Background

In the current study, estimation of lamivudine (LMU) by UV spectroscopy, reverse-phase HPLC (RP-HPLC) and HPTLC methods in tablet formulation was developed, and comparative studies between the methods were investigated by analytical results and statistical test analysis of variance (ANOVA) to find out best method. In the UV spectral method, LMU was quantified at 271 nm absorption maxima using methanol as the solvent. In the RP-HPLC method, the Shimadzu C18 column (250 mm × 4.6 mm i.d., 5 µm particle size) was employed for chromatographic separation. The mobile phase used consists of methanol: water (70:30 v/v) in an isocratic mode with a 1.0 mL/min flow rate. In the HPTLC method, the chromatogram was developed on a pre-coated plate of silica gel 60 F254 with a mobile phase composition of chloroform: methanol (8:2 v/v). The quantification was performed at an absorbance mode of 271 nm by densitometry. The methods were validated according to the International Conference on Harmonization (ICH) guideline Q2 (R1). The degradation conditions were employed as per ICH guidelines Q1A(R2) and Q1B which include acid, alkaline, neutral, thermal and photostability to determine the intrinsic stability of the drug in varied environmental conditions.

Results

LMU absorption maxima was found to be 271 nm. The retention time of LMU was 3.125 min, and the total analysis time was 5 min. The R_f value of LMU was 0.49–0.62. The methods were linear within 2–12 μg/mL range. The correlation coefficient (r²) for UV, HPLC and HPTLC was 0.9980, 0.9993 and 0.9988, and percent recoveries were calculated as 98.40–100.52%, 99.27–101.18% and 98.01–100.30%, respectively, with percentage relative standard deviation (RSD) less than 2% showing that methods were precise and accurate.

Conclusion

Developed UV, RP-HPLC and HPTLC methods are free from intervention caused by excipients present in tablets and thus can be used for regular quantitative analysis of LMU in tablet formulation. Based on analytical results and statistical tests, ANOVA, it is inferred that the HPLC method is best for LMU quantification tablet formulation due to its high reproducibility, good retention time and sensitivity; it has a higher percent recovery and has less analysis time, i.e., 5 min. The degradation peaks were well separated from the LMU peak indicating stability of the HPLC method.

Background

In this work, we represent synthesis, in silico analysis and biological activity of 1,4 diazepine linked piperidine derivatives (6a–6o). All the derivatives were screened for their anti-microbial activity against gram-positive (Staphylococcus aureus, Bacillus Subtills, Bacillus megaterium) and gram-negative (Escherichia coli, Pseudonymous, Shigella sp.) bacteria. Compounds were synthesized from reaction of tert-butyl 1,4-diazepane-1-carboxylic, butyryl chloride and varied aromatic aldehyde, further characterized by ¹H NMR and LCMS spectral techniques.

Result

Using ampicillin as a positive control, the synthetic compounds 6a–6o were tested for their in-silico study and experimental anti-microbial activity against gram-positive (Staphylococcus aureus, Bacillus Subtills, Bacillus megaterium) and gram-negative (Escherichia coli, Pseudonymous, Shigella sp.) bacteria. According to in vitro assay compound 6a, compound 6c, compound 6d, compound 6m and compound 6I showed higher activity against all the tested strains. Molecule 6i, compound 6j, compound 6k, compound 6f has good to moderate antibacterial activity. DFT computations were used to optimize the molecular geometry at the B3LYP/6-31G (d, p) theoretical level. The corresponding energy values of molecular orbitals were visualized using optimized geometries. Moreover, Auto Dock Vina 1.2.0 is used to assess molecular docking against two target proteins, Bacillus subtilis (PDB ID: 6UF6) and Protease Vulgaris (PDB ID: 5HXW). The target molecule 6b displayed the best binding energies for both. Additionally, we calculated the ADME for each molecule (6a–6o).

Conclusion

All fifteen synthesized compounds were screened for their in vitro and in silico analysis. In vitro analysis for anti-microbial activity was carried out against gram-positive (Staphylococcus aureus, Bacillus Subtills, Bacillus megaterium) and gram-negative (Escherichia coli, Pseudonymous, Shigella sp.) bacteria and compound 6a, compound 6c, compound 6d, compound 6m and compound 6I exhibits more potent activity towards all tested strains. Molecular docking is performed against target proteins, L-amino acid deaminase from Proteus Vulgaris and LcpA ligase from Bacillus subtilis, representing the Gram-negative bacterium and Gram-positive bacterium, respectively. Compound 6b showed the highest no. of interaction with protein according to molecular docking. With the advent of innovative techniques like ADME, we select their hit compounds early on and anticipate future pharmacokinetic and pharmacodynamic benefits and drawbacks of these promising therapeutic candidates.

Graphical abstract

Background

Phellinus fastuosus is a wood-eating medicinal fungus from Western Ghats of India. Therefore, we investigated hypoglycemic and hepatoprotective effects of P. fastuosus aqueous extract on streptozotocin-induced diabetic and carbon tetrachloride (CCl₄) induced hepatotoxicity in rats, respectively.

Result

As compared to the diabetic control group, a 400 mg/kg dose had significant hypoglycemic effects, including a reduction in blood glucose (24.44%) and gain in body weight. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity reduced by 31.81% and 32.84%, respectively, were also noted, along with decreases in triglycerides (24.32%) and cholesterol (25.89%) levels. The albumin, bilirubin and creatinine levels were also significantly reduced after administration of P. fastuosus extract in diabetic rats. Administration of P. fastuosus extract showed a substantial decrease in the activity of ALT, AST, alkaline phosphatase (ALP), catalase (CAT) and superoxide dismutase (SOD) in addition a decrease in the level of lipid peroxidation (LPO) as compared to CCl₄-intoxicated rats. The cumulative effect of CCl₄ increased the erythrocyte membrane peroxidation, whereas P. fastuosus extract reduced the cholesterol and increased phospholipid, thus preventing the alteration of membrane fluidity as compared to CCl₄-intoxicated rats. FTIR and HR-LC-MS-based metabolic profiling revealed the presence of various functional groups and bioactive metabolites.

Conclusion

The extract showed the hypoglycemic and hepatoprotective effects due to the presence of various bioactive metabolites. Exploration of therapeutic potential of P. fastuosus using bioassay-guided fractionation is needed.

Background

The escalating concern regarding the environmental impact of plastic waste necessitates the adoption of biodegradable methodologies to curtail its adverse effects. A profound comprehension of the intricate interplay between bacteria and polymers becomes imperative for devising effective solutions to address plastic-induced environmental challenges.

Main body of the abstract

Numerous microorganisms have evolved specialized mechanisms for the degradation of plastics, rendering them amenable to application in green chemistry for the elimination of hazardous plastics from the ecosystem. This article offers a comprehensive survey of contemporary microbial bioremediation approaches geared towards augmenting plastic waste management and ameliorating plastic pollution. Emphasis is placed on elucidating the potential of microorganisms in mitigating the deleterious repercussions of plastics on ecosystems and human health, underscoring the significance of advanced strategies in green chemistry for sustainable plastic pollution mitigation.

Short conclusion

Current research emphasizes the effectiveness of naturally occurring soil microorganisms, particularly fungi like Aspergillus and bacteria like Bacillus, in breaking down plastics. To harness this potential on a broader scale, optimization of microbial activity conditions and pre-treatment with environmentally beneficial compounds are essential.

Background

Carbazoles are an important class of heterocyclic aromatic compounds that contain nitrogen atom in the ring. They have a large-conjugated system, attractive “electrical and charge-transport properties”, and the ability to efficiently incorporate different functional groups into the structurally inflexible carbazolyl ring.

Main text

Carbazole derivative ECCA acts as an anticancer agent by reactivating the P53 molecular signaling pathway; similarly, some other derivatives of carbazole show antifungal activity by acting on the RAS-MAPK pathway. Carbazole derivatives also show their effect on inflammation by inhibiting the p38 mitogen-activated protein kinase signaling pathway by stopping the conversion of DAXX protein into ASK-1. By modifying the AKT molecular signaling pathway through boosting protein phosphatase activity in the brain, they show anti-Alzheimer’s activity and also by translocating the GLUT4 these are effective against diabetes.

Conclusion

After exploring the literature on carbazole, it was found that carbazole has an immeasurably great potential for the treatment of various diseases as the carbazole nucleus leads to various synthesized derivatives which are used for their pharmacological activities. So there is a need to explore carbazole for some newer drugs.

Background

Allergic disorders, prevalent global health concerns, afflict a substantial portion of the world’s population. These maladies result from an exaggerated immune system response to ordinarily innocuous substances, such as pollen, dust mites, and specific dietary components. Clinical manifestations of this heightened immune response include itching, swelling, and respiratory impairment, often accompanied by releasing mediators like histamine. The pathophysiological mechanisms of allergy disorders are intricate, arising from a complex interplay between genetic and environmental factors. While clinical presentations may vary, all allergy conditions share a common foundation in the dysregulated immune response to allergens.

Result

The current aim of this study was to identify innovative anti-allergic agents capable of inhibiting histamine and effectively mitigating allergic reactions by utilizing the computer-aided drug design approach by discovery studio (DS) 2022 v 23.1.1 package. The overarching aim was identifying potential drug candidates targeting the active site within the histamine H1 receptor complex; therefore, a collection of 4000 small druggable compounds was curated from ZINC, PubChem, and DRUG BANK databases sources. Four compounds appeared as promising candidates after assessing docking scores and binding energies. Notably, Compound ID 34154, recognized as tymazoline, showed the highest affinity for the H1 receptor of 3RZE, suggesting it may be the most promising choice for more research. Further chemoinformatic and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analyses were conducted to assess the drug-like qualities of this chosen molecule. In addition, bioisosteric substitution techniques were employed to enhance tymazoline’s ADMET characteristics.

Conclusion

Tymazoline shows strong binding affinity with 3RZE and verified all the drug-likeness criteria to inhibit the allergic disorders. Furthermore, molecular dynamics (MD) studies corroborated tymazoline’s potential as an anti-allergic agent, demonstrating contact between the ligand and the receptor that is well defined and stable.

Background

The management of pain presents a significant challenge in healthcare, particularly in cases where conventional therapies prove inadequate. In response to this need, this study aims to devise two innovative UV spectrophotometric techniques rooted in the principles of green analytical chemistry for the analysis of Aceclofenac (ACE), Paracetamol (PAR), and Tramadol (TRM) in both bulk and tablet forms.

Results

Utilizing advanced mathematical methodologies such as the double divisor ratio spectra method and area under the curve, the concentrations of these drugs were accurately determined. Validation of the developed methods adhered to the guidelines outlined by the International Council for Harmonisation in the Q2 (R1), revealing linear calibration curves for ACE (8–12 µg/mL), PAR (22.75–35.75 µg/mL), and TRM (2.62–4.12 µg/mL). Furthermore, statistical analyses employing Student’s t test and F test were conducted to ensure the robustness of the proposed method. The evaluation of environmental impact through green metric tools confirmed the eco-friendliness of the proposed methodologies.

Conclusion

The assessment performed utilizing green metric tools has substantiated the environmental sustainability of the proposed approach. Thus, this methodology offers accurate and reliable outcomes for the determination of three drugs, as indicated by the complete overlap observed in the zero-order spectra.

Background

Hepatic cancer endures a major health scourge as the consequence of a high incidence of > 1 million cases by 2025. Plant-based products are typically effective in ameliorating health conditions. Pomegranate peel extract (PE) with its high polyphenolic content has anticancer effects against different types of cancer. Herein, we aimed to maximize the PE chemotherapeutic efficacy by loading it in a suitable delivery system to overcome the limitations of PE, to control its release and to achieve liver targeting.

Method

A nanoprecipitation procedure was adopted to incorporate PE into biodegradable and biocompatible natural polymeric zein (ZN)-based nanoparticles (NPs) (PE-ZN NPs). A full factorial design (2²× 3¹) was developed to study the effects of the formulation variables, namely pH of dispersion, PE-to-ZN ratio and surfactant concentration.

Results

The optimization revealed a surfactant-free stable PE-ZN NPs formula with a small particle size of 99.5 ± 6.43 nm, high PE encapsulation efficiency % of 99.31% ± 3.64 (w/w) and controlled release of PE over 24 h.

Conclusion

Moreover, the cytotoxicity of the optimum formula against hepatic cancer HepG2 cell lines was assessed and attained about a 2.5-fold reduction in the inhibitory concentration (IC₅₀) values compared to the free PE affording a promising green platform to combat hepatic cancer.

Graphical abstract

Background

Acyclovir is an anti-viral medication given to treat herpes simplex and herpes zoster infection. In some severe conditions such as herpes encephalitis, acyclovir is administered intravenously. However, high acyclovir doses may cause acute kidney injury and low acyclovir dose may predispose the patient to inadequate exposure to acyclovir which could be fatal in some conditions. In such cases, the acyclovir plasma concentrations will potentially guide the diagnosis and management of the kidney injury. In this study, we provide a simple and time-efficient method for analyzing acyclovir in human plasma using high-performance liquid chromatography (HPLC).

Results

The process starts with a single protein precipitation step by adding acetonitrile to deproteinize 300 µL of plasma. The chromatographic separation conditions consist of a mobile phase of water: methanol (97:3, v/v), a flow rate of 1 mL/min, a run time of 17 min, and a detection wavelength of 254 nm. The calibration curve was linear over the range of (0.70–60 mg/L) (r² ˃ 0.99). The retention times of acyclovir and the internal standard were around 15 and 12 min, respectively. The intra-day and inter-day analysis of acyclovir in plasma using this method exhibited accuracy and precision of less than 7%, which lies within the acceptable range. Different greenness assessment tools confirmed that the proposed method is eco-friendly.

Conclusion

The proposed method of analysis of acyclovir in the plasma using HPLC is simple, green and accurate method. This method could be applied in clinical settings where monitoring acyclovir concentrations is essential as it has wide range of the concentrations that could be detected.