Journal of pharmaceutical analysis最新文献

The acute toxicity of cyanide and its pharmaceutical residues has fueled interest in the development of analytical methods for its determination, particularly for sodium nitroprusside (SNP), a widely used vasodilator with potential cyanide residues. In this study, a dual-chamber derivatization bottle was designed to establish an interconnected gas environment, thereby facilitating chloramine T-mediated cyanide conversion to cyanogen chloride (CNCl) without direct contact with SNP. Subsequent determination of the analytes was undertaken using a headspace-gas chromatography-electron capture detector (HS-GC-ECD). The challenges of analyzing cyanide and the rapid degradation of SNP were addressed simultaneously. The method was subjected to rigorous validation, encompassing specificity, linearity, limit of detection (LOD), limit of quantitation (LOQ), accuracy, precision, and robustness. The validation process revealed a notable degree of linearity within the range of 0.012-1.56 μg/mL, with a LOQ of 12.0 ng/mL. The method was found to be both accurate and precise, thus satisfying the requisite criteria. This method facilitates reliable cyanide monitoring in degradation-prone pharmaceuticals.

Optical biosensors are gaining popularity owing to their portability, miniaturization, no requirement for additional attachments, and rapid responsiveness. These features render them suitable for various applications including at-home diagnostics, pharmacology, and continuous molecular monitoring. The integration of functionalized low-dimensional nanomaterials (zero-dimensional (0D), 1D, 2D, and 3D) has redirected focus towards the design, fabrication, and optimization of optical biosensors. This review summarizes the fundamental mechanisms underlying optical biosensing. The key mechanisms include localized surface plasmon resonance (LSPR), photoluminescence (PL), surface enhancement Raman scattering (SERS), nanozyme-based colorimetric strategies, chemiluminescence, bioluminescence, and electrochemiluminescence. The advantages of various low-dimensional nanomaterials for different types of optical biosensors are presented. This comparison emphasizes their potential superiority in targeted biosensing applications. Therefore, promoting optical biosensing techniques and recent developments in advanced biosensing strategies for biomedical research and biopharmaceutical applications are necessary to establish their future directions.

Urinary tract infections (UTIs) have become a major health concern globally, necessitating effective treatments for mitigating discomfort and avert complications. The uropathogens commonly associated with UTIs in humans such as Bacillus species, Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Escherichia coli (E. coli) are progressively developing resistance to current treatments and medications. The ancient wisdom of Ayurvedic medicines and its holistic approach can contribute to UTI treatment due to its lower toxicity, effectiveness against pathogens, and cost efficiency making it a viable option to complement or replace conventional treatments. This review delineates the key probable interactions between the bioactive components of antibacterial herbal drugs and UTI pathogens. Herbal drugs are rich in antioxidants such as flavonoids and polyphenols which can effectively neutralize free radicals and inhibit the formation of bacterial biofilms. These actions help alleviate oxidative stress and contribute to their anti-inflammatory effects. Certain specific herbs traditionally identified for their anti-inflammatory and antibacterial activity have been evaluated for their efficacy towards treatment of UTIs. Finally, the review addresses the challenges associated with herbal treatments of UTIs including issues related to standardization, dosage, and potential interactions with conventional medications that need to be overcome for broader acceptance and application.

Cardiometabolic diseases (CMDs) represent an ongoing major global health challenge, driven by complex interactions among genetic, environmental, microbiome-related, and other factors. While small-molecule drugs and lifestyle interventions can provide clinical benefits, they are possible to be constrained by the limited druggability of key target proteins, the potential risks of off-target effects, and difficulties in maintaining long-term adherence. In recent years, gut microbiota modulation and macromolecular drugs have emerged as promising therapeutic strategies. Gut microbiota modulation (e.g., probiotics, synbiotics, or natural products) exerts systemic metabolic and immune effects, supporting a therapeutic approach targeting multiple diseases. Meanwhile, macromolecular drugs (e.g., peptides, antibodies, and small nucleic acids) offer precise, pathway-targeted interventions. Despite advancements, limitations remain in addressing ethical considerations in microbiota modulation and optimizing targeted delivery systems, all of which may hinder clinical translation. Here, we provide a comprehensive overview of therapeutic approaches for CMDs, with a focus on obesity, type 2 diabetes mellitus (T2DM), and atherosclerosis (AS). The review is structured around three key aspects: i) conventional therapies, including small-molecule drugs and lifestyle interventions; ii) emerging therapies encompassing gut microbiota modulation, macromolecular drugs, and their interactions; and iii) challenges and opportunities for comorbidity management, microbiota ethics, and artificial intelligence (AI)-driven therapeutic optimization. We hope this review enhances the understanding of small-molecule drugs, lifestyle interventions, gut microbiota modulation, and macromolecular drugs in the management of CMDs, thereby fostering medical innovation and contributing to the development of system-based comprehensive therapeutic paradigms.

Chronic joint pain in rheumatoid arthritis (RA) represents a persistent therapeutic challenge, and although luteolin (LUT) exhibits established anti-inflammatory properties, its precise mechanism for alleviating RA-associated chronic pain remains undefined. Through systematic investigation in collagen-induced arthritis (CIA) mice, we demonstrated that LUT administration effectively attenuated chronic pain by modulating spinal cluster of differentiation 4 positive T (CD4⁺ T) cell dynamics and suppressing microglial activation. Integrated multi-omics profiling (cleavage under targets and tagmentation (CUT&Tag), RNA sequencing (RNA-seq), and metabolomics) coupled with functional validation revealed nuclear factor of activated T cells 2 (NFATC2) as the central transcriptional regulator governing T helper 17 (Th17) cell differentiation and spinal infiltration through protein kinase C epsilon (PRKCE)-signal transducer and activator of transcription 3 (STAT3) signaling transduction. Significantly, our mechanistic studies uncovered a previously unrecognized epigenetic cascade: LUT-mediated suppression of lactate dehydrogenase A (LDHA) activity disrupts glycolysis-fueled histone 3 lysine 9 lactylation (H3K9la), thereby epigenetically silencing NFATC2 transcription. Translational studies using RA patient-derived CD4⁺ T cells confirmed LUT's capacity to normalize pathological hyperactivity of the LDHA/H3K9la/NFATC2 axis, concomitantly regulating CD4⁺ T dynamics. Biophysical validation through molecular docking, surface plasmon resonance (SPR), and molecular dynamics (MD) simulations established LUT's direct binding to LDHA with high affinity. Collectively, these findings delineate a novel therapeutic paradigm wherein LUT alleviates RA-associated chronic pain by orchestrating Th17 differentiation and migratory capacity through coordinated blockade of the LDHA-H3K9la-NFATC2 signaling network, highlighting its potential as a disease-modifying agent for chronic pain management in RA.

The lack of a cell-based screening method limits urate-lowering drug development. A novel method combining aptamer sensor array (ASA), exonuclease III (Exo III)- powered 3D DNA walker (DW), and linear discriminant analysis (LDA) was developed for detecting uric acid (UA) in cell lysates, referred to as ASA-Exo III-DW-LDA. Three aptamers (Apts) with different affinities for UA and its structurally similar compound, xanthine (Xan), were used to design the ASA. The combination of ASA and Exo III-DW enabled the detection of UA at the picomolar level, whereas LDA was employed to differentiate UA signals from the mixed signals of UA and Xan. Significantly, Pearson correlation analysis revealed a strong correlation between our method and the ¹⁴C radioactive labeling method for urate anion exchanger 1 (URAT1) inhibitors, with r = 0.9880 for lesinurad and r = 0.9777 for benzbromarone. Using our method, kaempferol was identified as a promising hit compound for inhibiting the URAT1, because of its low half-maximal inhibitory concentration (IC₅₀) (18.96 μM) low toxicity in mouse renal tubular epithelial cells (mTECs), and significant urate-lowering effect in hyperuricemic mice at 5 mg/kg. Overall, this method is sensitive, cost-effective and safe, offering a novel strategy for routine urate-lowering drug screening in standard laboratories.

Chemical integrity is indispensable for advancing healthcare by ensuring the availability of high quality, safe, and effective pharmaceutical products. Ingredient quantification is particularly pivotal in this process. Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for both qualitative and quantitative analysis for complex systems. Compared with 1D quantitative ¹H NMR (¹H qNMR), quantitative ¹³C NMR (¹³C qNMR) holds some unique advantages. This technique offers a broader chemical shift range and the resulting much lesser signal overlap compare to ¹H NMR spectroscopy. This review summarizes relevant studies on the use of ¹³C qNMR as a quantification technique, along with a focus on quantitative principles, influencing factors, and technical improvements of ¹³C NMR. The review also highlights its applicability in quantifying diverse molecular structures in pharmaceutical analysis. In addition, potential of low-field NMR, artificial intelligence (AI)-driven method development, and hyphenation of NMR with other techniques for ¹³C qNMR analysis is discussed and summarized as well. As a versatile method, ¹³C qNMR holds great potential, and ongoing research is expected to unlock its full capabilities and expand its range of applications.

Glaucoma represents a predominant worldwide etiology of permanent vision impairment; it is clinically manifested through progressive neuronal atrophy in retinal ganglion cells (RGCs) and is accompanied by axonal degeneration in the optic pathway. Given the limited efficacy of conventional intraocular pressure-lowering therapies in halting RGC degeneration, the exploration of novel neuroprotective strategies has become imperative. An increasing amount of research emphasizes the pathogenic role of ferroptosis, a metal ion-associated programmed cellular demise mechanism recently implicated in neurodegenerative cascades, as a pivotal executor of RGC demise and putative central mechanism in glaucomatous pathology. This comprehensive review systematically examines the mechanistic interplay between ferroptosis and established contributors to glaucomatous optic neuropathy, including oxidative stress, mitochondrial dysfunction, glutamate excitotoxicity, and neuroinflammation. We provide evidence demonstrating that retinal ferroptosis is associated with the death of RGCs and discuss current therapeutic strategies to mitigate retinal ferroptosis, including treatments with natural products and gene therapy. Furthermore, by understanding ferroptosis, we provide insights into potential therapeutic targets and offer valuable directions for future research and clinical applications.

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Pyrrolizidine alkaloids (PAs), a class of secondary metabolites widely distributed in plants and the accidental ingestion or improper use of foods and herbs containing PAs, can lead to irreversible liver damage. Considering that the toxic mechanism of PAs is closely associated with metabolism, the hepatotoxicity was analyzed from the perspective of lipid metabolism. An integrated analytical approach was employed, combining mass spectrometry imaging (MSI) with liquid chromatography-mass spectrometry (LC-MS), to comprehensively investigate the spatial and temporal dynamics of lipid metabolites during PA exposure. The final lipidomics results combined with RNA sequencing showed that time-dependent changes in metabolite levels after the administration of PAs, involving the pathways of fatty acids, glycerophospholipids, glycerolipids and sphingolipids. Among them, phosphatidylcholines (PC), phosphatidylethanolamines (PE), phosphatidylinositols (PI) and sphingomyelins (SM) were downregulated to varying degrees within 0-24 h, while phosphatidylglycerol (PG), ceramides (Cer), diacylglycerols (DG) and triacylglycerols (TG) were upregulated. Notably, certain lipids exhibited distinct spatial distributions; for example, elevated levels of TG (56:13) were localized near the hepatic portal vein. Subsequently, the changes of lipid subclasses recovered within 24-48 h. Transcriptome RNA sequencing was used to enrich for key pathway-related differential genes Pemt, Gpat, etc. to explain the regulation of the hepatotoxic lipid pathway. The integration of MSI with LC-MS spectroscopy of endogenous metabolites provided intuitive insights into the alterations and spatial distribution of lipid metabolism in mice. Consequently, this study may enhance specific assessments and facilitate early diagnosis of acute toxicity associated with PAs.