Journal of Pharmaceutical Analysis

Current diagnostic and therapeutic strategies for COVID-19

Binbin Chen, Mengli Liu, Chengzhi Huang

2021, 11(2): 129-137. doi: 10.1016/j.jpha.2020.12.001

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The outbreak and spread of novel coronavirus disease 2019 (COVID-19) with pandemic features, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have greatly threatened global public health. Given the perniciousness of COVID-19 pandemic, acquiring a deeper understanding of this viral illness is critical for the development of new vaccines and therapeutic options. In this review, we introduce the systematic evolution of coronaviruses and the structural characteristics of SARS-CoV-2. We also summarize the current diagnostic tools and therapeutic strategies for COVID-19.

Chemically modified carbon-based electrodes for the determination of paracetamol in drugs and biological samples

Wafaa Boumya, Nawal Taoufik, Mounia Achak, Noureddine Barka

2021, 11(2): 138-154. doi: 10.1016/j.jpha.2020.11.003

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Paracetamol is a non-steroidal, anti-inflammatory drug widely used in pharmaceutical applications for its sturdy, antipyretic and analgesic action. However, an overdose of paracetamol can cause fulminant hepatic necrosis and other toxic effects. Thus, the development of advantageous analytical tools to detect and determine paracetamol is required. Due to simplicity, higher sensitivity and selectivity as well as costefficiency, electrochemical sensors were fully investigated in last decades. This review describes the advancements made in the development of electrochemical sensors for the paracetamol detection and quantification in pharmaceutical and biological samples. The progress made in electrochemical sensors for the selective detection of paracetamol in the last 10 years was examined, with a special focus on highly innovative features introduced by nanotechnology. As the literature is rather extensive, we tried to simplify this work by summarizing and grouping electrochemical sensors according to the by which manner their substrates were chemically modified and the analytical performances obtained.

Development of chromatographic technologies for the quality control of Traditional Chinese Medicine in the Chinese Pharmacopoeia

Ming-Rui Shen, Yi He, Shang-Mei Shi

2021, 11(2): 155-162. doi: 10.1016/j.jpha.2020.11.008

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As an important branch of medicine, Traditional Chinese Medicine (TCM) has been applied for the treatment of diseases for thousands of years in China and other countries in East Asia. The Chinese Pharmacopoeia (ChP) is a drug code formulated by the Chinese government, and it includes a special volume for the monographs of TCM, which plays an important role in ensuring the quality of drugs. The use of quality control technology has always been a complex and important factor in TCM. Owing to the chemical diversity of TCM, chromatography technology has been proven to be a comprehensive strategy for the assessment of the overall quality of TCM and has become the main analytical method in the ChP. This article provides an overview of the classical and modern chromatographic technologies applied in the ChP, and summarizes the advantages and disadvantages of each technique in the TCM monographs. In 2020, the new edition of the ChP (the 2020 edition) has been implemented at the end of 2020. This paper also contains a brief introduction about the application of chromatographic technologies in the new edition of the ChP.

Design and preparation of a new multi-targeted drug delivery system using multifunctional nanoparticles for co-delivery of siRNA and paclitaxel

Sara Hosayni Nasab, Amin Amani, Hossein Ali Ebrahimi, Ali Asghar Hamidi

2021, 11(2): 163-173. doi: 10.1016/j.jpha.2020.04.005

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Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel (PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid (FA) and glucose (Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCo-polyethyleneimine (FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol (PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu (NPsB) and FeCo-PEI-PLA-PEG-FA/Glu (NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX. Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.

The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors

Mirza Muhammad Faran Ashraf Baig, Chengfei Zhang, Muhammad Furqan Akhtar, Ammara Saleem, Jahanzeb Mudassir

2021, 11(2): 174-182. doi: 10.1016/j.jpha.2020.10.003

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DNA-nanotechnology-based nano-architecture scaffolds based on circular strands were designed in the form of DNA-nanowires (DNA-NWs) as a polymer of DNA-triangles. Circularizing a scaffold strand (84-NT) was the critical step followed by annealing with various staple strands to make stiff DNA-triangles. Atomic force microcopy (AFM), native polyacrylamide gel electrophoresis (PAGE), UV-analysis, MTT-assay, flow cytometry, and confocal imaging were performed to assess the formulated DNA-NWs and cisplatin (CPT) loading. The AFM and confocal microscopy images revealed a uniform shape and size distribution of the DNA-NWs, with lengths ranging from 2 to 4 μm and diameters ranging from 150 to 300 nm. One sharp band at the top of the lane (500 bp level) with the loss of electrophoretic mobility during the PAGE (native) gel analysis revealed the successful fabrication of DNA-NWs. The loading efficiency of CPT ranged from 66.85% to 97.35%. MTT and flow cytometry results showed biocompatibility of the blank DNA-NWs even at 95% concentration compared with the CPT-loaded DNA-NWs. The CPT-loaded DNA-NWs exhibited enhanced apoptosis (22%) compared to the apoptosis (7%) induced by the blank DNA-NWs. The release of CPT from the DNA-NWs was sustained at < 75% for 6 h in the presence of serum, demonstrating suitability for systemic applications. The IC₅₀ of CPT@DNA-NWs was reduced to 12.8 nM CPT, as compared with the free CPT solution exhibiting an IC₅₀ of 51.2 nM. Confocal imaging revealed the targetability, surface binding, and slow internalization of the DNA-NWs in the scavenger-receptor-rich cancer cell line (HepG2) compared with the control cell line.

A dual-signal sensor for the analysis of parathion-methyl using silver nanoparticles modified with graphitic carbon nitride

Yuan Li, Mengqi Wan, Guosheng Yan, Ping Qiu, Xiaolei Wang

2021, 11(2): 183-190. doi: 10.1016/j.jpha.2020.04.007

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A highly sensitive and selective method was developed for both UV–vis spectrophotometric and fluorimetric determination of organophosphorus pesticides (OPs). This method used silver nanoparticles (AgNPs) modified with graphitic carbon nitride (g-C₃N₄). The AgNPs reduced the fluorescence intensity of g-C₃N₄. Acetylthiocholine (ATCh) could be catalytically hydrolyzed by acetylcholinesterase (AChE) to form thiocholine, which induces aggregation of the AgNPs. This aggregation led to the recovery of the blue fluorescence of g-C₃N₄, with excitation/emission peaks at 310/460 nm. This fluorescence intensity could be reduced again in the presence of OPs because of the inhibitory effect of OPs on the activity of AChE. The degree of reduction was found to be proportional to the concentration of OPs, and the limit of fluorometric detection was 0.0324 μg/L (S/N = 3). In addition, the absorption of the g-C₃N₄/AgNPs at 390 nm decreased because of the aggregation of the AgNPs, but was recovered in presence of OPs because of the inhibition of enzyme activity by OPs. This method was successfully applied to the analysis of parathion-methyl in real samples.

Curcumin encapsulated dual cross linked sodium alginate/montmorillonite polymeric composite beads for controlled drug delivery

O. Sreekanth Reddy, M.C.S. Subha, T. Jithendra, C. Madhavi, K. Chowdoji Rao

2021, 11(2): 191-199. doi: 10.1016/j.jpha.2020.07.002

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The aim of the present work is fabrication of dual cross linked sodium alginate (SA)/montmorillonite (MMT) microbeads as a potential drug vehicle for extended release of curcumin (CUR). The microbeads were prepared using in situ ion-exchange followed by simple ionotropic gelation technique. The developed beads were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (X-RD) and scanning electron microscopy (SEM). The effect of MMT on encapsulation efficiency of CUR and intercalation kinetics was investigated. Dynamic swelling study and in vitro release study were investigated in simulated intestinal fluid (pH 7.4) and simulated gastric fluid (pH 1.2) at 37 °C. Results suggested that both the swelling and in vitro release studies were influenced by the pH of test media, which might be suitable for intestinal drug delivery. The release mechanism was analyzed by fitting the release data into Korsmeyer-Peppas equation.

Herb-drug interaction in the protective effect of Alpinia officinarum against gastric injury induced by indomethacin based on pharmacokinetic, tissue distribution and excretion studies in rats

Xuguang Zhang, Zhenrui Xie, Xun Chen, Junqiang Qiu, Yinfeng Tan, Xiaoliang Li, Hailong Li, Junqing Zhang

2021, 11(2): 200-209. doi: 10.1016/j.jpha.2020.05.009

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Alpinia officinarum Hance of the Chinese traditional herb for the treatment of emesis, abdominal pain and diarrhea has been used to counteract gastric disease induced by indomethacin in rats without obvious side effects. However, the role of herb-drug interaction between indomethacin and A. officinarum based on pharmacokinetic, tissue distribution and excretion still remains unknown. In this study, an ultra-fast liquid-tandem mass spectrometry (UFLC-MS/MS) method was developed for simultaneous determination of indomethacin and its three metabolites, O-desmethylindomethacin (ODI), deschlorobenzoylindomethacin (NDI) and indomethacin acyl-β-D-glucuronide (IDAβG) by oral administration of indomethacin solution with and without the ethanolic extract of A. officinarum and applied to comparative pharmacokinetic, tissue distribution and excretion studies. Our results clarified that oral administration of A. officinarum produced significant alterations in the pharmacokinetic parameters of indomethacin. And the pharmacokinetic interaction between indomethacin and A. officinarum reduced the systemic exposure of indomethacin and increased its elimination. Tissue distribution results demonstrated that co-administration of A. Officinarum could not reduce the accumulation of indomethacin in the target tissue of the stomach, but could accelerate the excretions of indomethacin and its three metabolites including ODI, NDI and IDAβG in the bile and feces of rats in the excretion study. Therefore, A. Officinarum might have a gastrointestinal protective effect through the interaction role with indomethacin based on the pharmacokinetics and excretion in rats.

Antimicrobial activity and mode of action of terpene linalyl anthranilate against carbapenemase-producing Klebsiella pneumoniae

Shun-Kai Yang, Khatijah Yusoff, Mokrish Ajat, Wai-Sum Yap, Swee-Hua Erin Lim, Kok-Song Lai

2021, 11(2): 210-219. doi: 10.1016/j.jpha.2020.05.014

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Mining of plant-derived antimicrobials is the major focus at current to counter antibiotic resistance. This study was conducted to characterize the antimicrobial activity and mode of action of linalyl anthranilate (LNA) against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). LNA alone exhibited bactericidal activity at 2.5% (V/V), and in combination with meropenem (MPM) at 1.25% (V/V). Comparative proteomic analysis showed a significant reduction in the number of cytoplasmic and membrane proteins, indicating membrane damage in LNA-treated KPC-KP cells. Up-regulation of oxidative stress regulator proteins and down-regulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that LNA increases both bacterial surface charge and membrane permeability. Ethidium bromide influx/efflux assay showed increased uptake of ethidium bromide in LNA-treated cells, inferring membrane damage. Furthermore, intracellular leakage of nucleic acid and proteins was detected upon LNA treatment. Scanning and transmission electron microscopies again revealed the breakage of bacterial membrane and loss of intracellular materials. LNA was found to induce oxidative stress by generating reactive oxygen species (ROS) that initiate lipid peroxidation and damage the bacterial membrane. In conclusion, LNA generates ROS, initiates lipid peroxidation, and damages the bacterial membrane, resulting in intracellular leakage and eventually killing the KPC-KP cells.

Neuroprotective effects of Ginkgo biloba dropping pills in Parkinson’s disease

Dingyi Yu, Pengli Zhang, Junying Li, Ting Liu, Yaodan Zhang, Qingqing Wang, Jianbing Zhang, Xiaoyan Lu, Xiaohui Fan

2021, 11(2): 220-231. doi: 10.1016/j.jpha.2020.06.002

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Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world; however, it lacks effective and safe treatments. Ginkgo biloba dropping pill (GBDP), a unique Chinese G. biloba leaf extract preparation, exhibits antioxidant and neuroprotective effects and has a potential as an alternative therapy for PD. Thus, the aims of this study were to evaluate the effects of GBDP in in vitro and in vivo PD models and to compare the chemical constituents and pharmacological activities of GBDP and the G. biloba extract EGb 761. Using liquid chromatography tandem-mass spectrometry, 46 GBDP constituents were identified. Principal component analysis identified differences in the chemical profiles of GBDP and EGb 761. A quantitative analysis of 12 constituents showed that GBDP had higher levels of several flavonoids and terpene trilactones than EGb 761, whereas EGb 761 had higher levels of organic acids. Moreover, we found that GBDP prevented 6-hydroxydopamine-induced dopaminergic neuron loss in zebrafish and improved cognitive impairment and neuronal damage in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice. Although similar effects were observed after EGb 761 treatment, the neuroprotective effects were greater after GBDP treatment on several endpoints. In addition, in vitro results suggested that the Akt/GSK3β pathway may be involved in the neuroprotective effects of GBDP. These findings demonstrated that GBDP have potential neuroprotective effects in the treatment of PD.

Taxifolin stability: In silico prediction and in vitro degradation with HPLC-UV/UPLC–ESI-MS monitoring

Fernanda Cristina Stenger Moura, Carmem Lúcia dos Santos Machado, Favero Reisdorfer Paula, Angélica Garcia Couto, Maurizio Ricci, Valdir Cechinel-Filho, Tiago J. Bonomini, Louis P. Sandjo, Tania Mari Bellé Bresolin

2021, 11(2): 232-240. doi: 10.1016/j.jpha.2020.06.008

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Taxifolin has a plethora of therapeutic activities and is currently isolated from the stem bark of the tree Larix gmelinni (Dahurian larch). It is a flavonoid of high commercial interest for its use in supplements or in antioxidant-rich functional foods. However, its poor stability and low bioavailability hinder the use of flavonoid in nutritional or pharmaceutical formulations. In this work, taxifolin isolated from the seeds of Mimusops balata, was evaluated by in silico stability prediction studies and in vitro forced degradation studies (acid and alkaline hydrolysis, oxidation, visible/UV radiation, dry/humid heating) monitored by high performance liquid chromatography with ultraviolet detection (HPLC-UV) and ultrahigh performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS). The in silico stability prediction studies indicated the most susceptible regions in the molecule to nucleophilic and electrophilic attacks, as well as the sites susceptible to oxidation. The in vitro forced degradation tests were in agreement with the in silico stability prediction, indicating that taxifolin is extremely unstable (class 1) under alkaline hydrolysis. In addition, taxifolin thermal degradation was increased by humidity. On the other hand, with respect to photosensitivity, taxifolin can be classified as class 4 (stable). Moreover, the alkaline degradation products were characterized by UPLC-ESI-MS/MS as dimers of taxifolin. These results enabled an understanding of the intrinsic lability of taxifolin, contributing to the development of stability-indicating methods, and of appropriate drug release systems, with the aims of preserving its stability and improving its bioavailability.

Diversity, novelty, antimicrobial activity, and new antibiotics of cultivable endophytic actinobacteria isolated from psammophytes collected from Taklamakan Desert

Ting Wang, Feina Li, Qinpei Lu, Gang Wu, Zhongke Jiang, Shaowei Liu, Xugela Habden, Elizaveta A. Razumova, Ilya A. Osterman, Petr V. Sergiev, Olga A. Dontsova, Xinxin Hu, Xuefu You, Chenghang Sun

2021, 11(2): 241-250. doi: 10.1016/j.jpha.2020.06.004

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Three hundred and twenty endophytic actinobacterial strains were isolated from psammophytes collected from Taklamakan Desert and identified. Among them, three strains already had been identified as new species of two genera and sixteen isolates showed relatively low 16S rRNA similarities < 98.6% to validly described species. Seventy-five of the isolates were selected as representative strains to screen antibacterial activity and mechanism. Forty-seven strains showed antagonistic activity against at least one of the indicator bacteria. Two Streptomyces strains produced bioactive compounds inducing DNA damage, and two Streptomyces strains produced bioactive compounds with inhibitory activity on protein biosynthesis. Notably, the strain Streptomyces sp. 8P21H-1 that demonstrated both strong antibacterial activity and inhibitory activity on protein biosynthesis was prioritized for exploring new antibiotics. Under the strategy of integrating genetics-based discovery program and MS/MS-based molecular networking, two new streptogramin-type antibiotics, i.e., acetyl-griseoviridin and desulphurizing griseoviridin, along with known griseoviridin, were isolated from the culture broth of strain 8P21H-1. Their chemical structures were determined by HR-MS, and 1D and 2D NMR. Desulphurizing griseoviridin and griseoviridin exhibited antibacterial activities by inhibiting translation.

Development of a rapid GC-FID method to simultaneously determine triethylamine, diisopropylamine, and 1,1,3,3-tetramethylguanidine residues in an active pharmaceutical ingredient

Minshan Shou, Haixiao Qiu

2021, 11(2): 251-256. doi: 10.1016/j.jpha.2020.06.007

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A rapid GC-FID method was developed to simultaneously determine residual levels of triethylamine (TEA), 1,1,3,3-tetramethylguanidine (TMG), and diisopropylamine (DIPA) in the synthetic route of an active pharmaceutical ingredient (API). Due to the severe absorption of amines on GC stationary phases, GC columns with various stationary phases were evaluated for optimal peak shape and reproducibility. The final conditions used the Agilent CP-Volamine column to resolve the three amines in 12 min. Various inlet liners were also screened to further improve the sensitivity of the analysis. The Restek Siltek® liner was selected to achieve the desired detectability for the method. The quantitation limits were 4, 3, and 4 μg/mL for TEA, DIPA, and TMG in the presence of API, respectively. All three amines showed good linearity (r > 0.999) and recoveries (> 90%) over the concentration range of 3 to 16 μg/mL. The testing of residual amines was initially performed at the penultimate stage of the synthesis. However, this work demonstrates that TMG can act as a proton sponge to react with salicylic acid, the counter ion of the penultimate, to form a volatile component that elutes at a different retention time. Consequently, in the final method, these three amines were monitored in the final API to circumvent the matrix interference. Key parameters of the method were qualified per method validation requirements in ICH guidelines. The method was successfully applied for batch testing during development and implemented as an in-process control procedure at manufacturing sites.

2021 Vol. 11, No. 2