Chemical composition combined with network pharmacology and quality markers analysis for the quality evaluation of Qing-fei-da-yuan granules.

Qing-fei-da-yuan granules (QFDYGs) had been proved to be an effective TCM prescription for treating coronavirus disease 2019 (COVID-19), which are composed of a variety of TCMs, and characterized by multiple components, multiple targets and overall regulation. It is meaningful to further study the chemical composition and pharmacology of QFDYGs for quality evaluation. However, due to the complexity of the components of QFDYGs, there are no reliable and simple analytical methods for current quality evaluation. In this work, antipyretic activity assessment of QFDYGs in the LPS-induced New Zealand rabbit model was carried out to verify the efficacy firstly. It was proved that QFDYGs can be used to relieve fever to help preventing or controlling the prevalence of influenza and pneumonia. Subsequently, UHPLC-ESI-QTOF-MS/MS combined with network pharmacology, quality markers and fingerprint analysis were used to establish the quality control condition. The chemical compositions were analyzed by UHPLC-ESI-QTOF-MS/MS, and 79 of them were identified, such as arecoline, mangiferin, paeoniflorin, etc. Then, the network pharmacology strategy based on 45 candidate components (CCs) in conjunction with influenza and pneumonia diseases was employed to screen the potential active ingredients. According to the drug-CCs-genes-diseases (D-CCs-G-D) networks, baicalein, honokiol, baicalin, paeoniflorin, saikosaponin A, glycyrrhizic acid and hesperidin were selected as quality markers. And a method for content determination of the 7 quality markers was established by optimizing extraction methods, chromatographic conditions and methodological verification. Finally, the quality of 15 batches of QFDYGs was evaluated by using the 7 quality markers combined with fingerprints and principal component analysis (PCA). The analyzed results showed that baicalin, paeoniflorin, glycyrrhizic acid and hesperidin were the high content and stable quality markers. QFDYGs were characterized by overall consistency and individual ingredient differences among the 15 batches. Our quality evaluation study will provide reference for the further development and research of QFDYGs.

[Determination of four antipyretic and analgesic drugs in water by solid-phase extraction coupled ultra-performance liquid chromatography-tandem mass spectrometry].

The widespread use of pharmaceutical and personal care products (PPCPs), including antipyretic and analgesic drugs, in the last two decades had led to the existence of PPCP residues in the environment, thus raising concerns about their pseudo-persistent nature and potential threat to human health. Generally, most of the detected contaminants are present at low levels (ranging from ng/L to µg/L) in environmental water. Therefore, advanced analytical methodologies are crucial to monitor the occurrence and distribution of antipyretic and analgesic drugs in environmental water. However, trace analysis of environmental pollutants is always challenging because it is necessary to extract analytes present in the sample at ultralow levels from complex environmental matrices. Therefore, an appropriate sample pretreatment is necessary to enrich the target compounds. Conventional solid-phase extraction materials show poor efficiency for the enrichment of antipyretic and analgesic drugs. We herein report a hydrophilic and lipophilic amphiphilic porous polymeric material GCHM (Guochuang hydrophilic material). GCHM was successfully prepared by a stepwise emulsification and micellization process using N-vinyl-2-pyrrolidone (NVP) and divinylbenzene (DVB) as raw materials. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of four antipyretic and analgesic drugs in water using our solid-phase extraction (SPE) column. The water samples were extracted and purified by the GCHM solid-phase extraction column, and then analyzed by UPLC-MS/MS. Gradient elution was carried out with 0.1% formic acid aqueous solution and acetonitrile as the mobile phase. The target analytes were separated on an ACQUITY UPLC HSS T3 column (100 mm×2.1 mm, 1.8 µm), and multiple reaction monitoring (MRM) was conducted in the positive electrospray ionization mode. The isotope internal standard method was used for quantitative correction. Comparison of the enrichment efficiencies of Oasis HLB, Bond Elut Plexa, and GCHM revealed that GCHM showed the best performance. Different pH values affecting the enrichment efficiency of the GCHM SPE column were optimized, and the matrix effect was evaluated. The results showed that the four target analytes gave the best enrichment effect on the SPE column at pH 7, and the matrix effect for each substance was between 82.8% and 102.2%, indicating obvious matrix removal after the water sample was purified by the GCHM SPE column. Good correlation coefficients (r) greater than 0.995 were observed for all the target compounds in the range of 1-100 µg/L. The method limits of quantitation (S/N=10) ranged from 1 ng/L to 5 ng/L. The corrected recoveries were 85.6% to 106.4%, and the relative standard deviations (RSD) were under 5.6%. The GCHM solid-phase extraction column is inexpensive and efficient, being suitable for the detection of the four antipyretic and analgesic drugs in water. Subsequently, the occurrence of these selected antipyretic and analgesic drugs in water samples from Shanghai, Jiangsu, and Guangdong provinces were studied. The GCHM column has potential advantages over the commercial imported SPE column and is worthy of widespread application. This column can also aid the enrichment and purification of other compounds with similar structures or properties in water.

[Analysis of three antipyretic analgesic drugs by open-tubular capillary electrochromatography].

The advantages of capillary electrophoresis, such as small sample consumption, high separation efficiency, and multiple separation modes, have been known for decades. However, exploring unique capillary electrophoresis techniques for the analysis of fluid drugs in living bio-systems remains an important and urgent task. Owing to the similar structures and mass-to-charge ratios of antipyretic analgesic drugs, efficient baseline separation of these analytes by capillary zone electrophoresis method cannot be easily achieved. Micellar electrokinetic chromatography can improve the baseline separation of these drugs, but the substantial amounts of non-volatile surfactants (such as sodium dodecyl sulfate, sodium dodecyl sulfonate, sodium deoxycholate and cetylammonium bromide) in running buffer solutions would pollute the ion source during mass spectrometric analysis. For this reason, it is difficult to analyze unknown drugs by capillary electrophoresis-electrospray ionization-mass spectrometry. To overcome these drawbacks, much attention has been paid to capillary electrochromatography (CEC) because combines the high separation efficiency of capillary electrophoresis with the high selectivity of high performance liquid chromatography (HPLC). Recent challenges encountered in open-tubular capillary electrochromatography (OT-CEC) expanding the range of suitable functional polymer monomers and improvement of the separation efficiency by tuning the characteristics of the polymer coatings without using any organic solvent additives. In this study, a protocol based on OT-CEC using a block co-polymer coating is proposed for the analysis of three test antipyretic analgesic drugs (4-aminoantipyrine, antipyrine and phenacetin), without adding organic solvents and surfactants in the running buffer solutions. First, an amphiphilic block co-poly(styrene-co-glycidyl methacrylate) (P(St-GMA)), was synthesized by reversible addition-fragmentation chain transfer polymerization under mild conditions. Then, P(St-GMA) was coated onto the capillary surface, and an OT-CEC analysis was performed. Next, the effect of some key factors, including the polymerization time for obtaining P(St-GMA) with different molecular weights, coating concentrations of the block copolymer, the species of the running buffer solutions, pH and concentrations of the running buffer solutions, and organic solvent additives, on the OT-CEC separation efficiency were investigated. Under the optimized conditions with 50.0 mmol/L NaAc-HAc as the running buffer solution at pH 5.7, the three test antipyretic analgesic drugs were base-line separated by the constructed OT-CEC system. Good linear relationships between peak area and concentration of the test analytes in the range of 8.0-2.5×103 µmol/L were obtained (R2 ≥ 0.995). The limits of detection (LODs) were 1.0-2.5 µmol/L. Furthermore, the reason for the OT-CEC separation efficiency was clarified based on the decreased electro-osmotic flow in the coated capillary compared with that in the uncoated capillary. Finally, the proposed OT-CEC assay without using any organic solvents and surfactants as additives was applied for analysis of the three test antipyretic analgesic drugs in rat serum samples. Importantly, it was found that despite peak tailing, the OT-CEC separation efficiency of the drugs was dramatically enhanced because the block co-polymer could self-assemble in the solution and form pseudo-micelles, which further increased the interactions between the P(St-GMA) and these drugs. Our results not only reveal the great potential of block co-polymer coatings in OT-CEC for the analysis of drugs in real biological samples, but also serve asa platform for the preparation of diverse block co-polymers to be used in OT-CEC analysis. We believe that in the near future, the peak tailing problem in OT-CEC analysis can be resolved by using the designed unique block co-polymers, which possess a greater number of functional sites, as coatings and by appropriately tuning the interactions between the analytes and the coatings.

Enhanced amperometric detection of paracetamol by immobilized cobalt ion on functionalized MWCNTs - Chitosan thin film.

In the present study, a nanocomposite of f-MWCNTs-chitosan-Co was prepared by the immobilization of Co(II) on f-MWCNTs-chitosan by a self-assembly method and used for the quantitative determination of paracetamol (PR). The composite was characterized by field emission scanning electron microscopy (FESEM) and energy dispersive x-ray analysis (EDX). The electroactivity of cobalt immobilized on f-MWCNTs-chitosan was assessed during the electro-oxidation of paracetamol. The prepared GCE modified f-MWCNTs/CTS-Co showed strong electrocatalytic activity towards the oxidation of PR. The electrochemical performances were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). Under favorable experimental conditions, differential pulse voltammetry showed a linear dynamic range between 0.1 and 400 µmol L-1 with a detection limit of 0.01 µmol L-1 for the PR solution. The fabricated sensor exhibited significant selectivity towards PR detection. The fabricated sensor was successfully applied for the determination of PR in commercial tablets and human serum sample.

A new analytical device incorporating a nitrogen doped lanthanum metal oxide with reduced graphene oxide sheets for paracetamol sensing.

The novel N-CeO2 nanoparticles decorated on reduced graphene oxide (N-CeO2@rGO) composite has been synthesized by sonochemical method. The characterization of as prepared nanocomposite was intensely performed by UV-Vis, FT-IR, EDX, FE-SEM, HR-TEM, XRD, and TGA analysis. The synthesized nanomaterial was further investigated for its selective and sensitive sensing of paracetamol (PM) based on a N-CeO2@rGO modified glassy carbon electrode. A distinct and improved reversible redox peak of PM is obtained at N-CeO2@rGO nanocomposite compared to the electrodes modified with N-CeO2 and rGO. It displays a very good performance with a wide linear range of 0.05-0.600 µM, a very low detection limit of 0.0098 µM (S/N = 3), a high sensitivity of 268 µA µM-1 cm-2 and short response time (<3 s). Also, the fabricated sensor shows a good sensibleness for the detection of PM in various tablet samples.

The Quality of Medicines Used in Children and Supplied by Private Pharmaceutical Wholesalers in Kinshasa, Democratic Republic of Congo: A Prospective Survey.

Poor-quality medicines are a threat to public health in many low- and middle-income countries, and prospective surveys are needed to inform corrective actions. Therefore, we conducted a cross-sectional survey on a sample of products used for children and available in the private market in Kinshasa, Democratic Republic Congo: amoxicillin (AX) and artemether/lumefantrine (AL), powders for suspension, and paracetamol (PC) tablets 500 mg. Overall, 417 products were covertly purchased from 61 wholesalers. To obtain a representative sample, the products were weighted on their market shares and a subset of 239 samples was randomly extracted to undergo in-depth visual inspection locally, and they were chemically assessed at two accredited laboratories in Belgium. Samples were defined of "poor-quality" if they failed to comply with at least one specification of the International Pharmacopoeia (for AL) or United States Pharmacopoeia 37 (for AX and PC). Results are reported according to the Medicine Quality Assessment Reporting Guideline. The visual inspection detected nonconformities in the aspects of antimalarial powders for suspension, and poor-quality labels across all medicine types. According to chemical analysis, 27.2% samples were of poor quality and 59.5% of AL samples were underdosed in artemether. Poor quality was more frequent for locally manufactured antimalarials (83.3%, P = 0.021; 86.4%, P = 0.022) and PC (4.8%, P = 0.000). The poor quality of the surveyed products may decrease the treatment's efficacy and favor the development of resistances to antimalarials. It is hoped that these findings may guide the corrective actions of the Democratic Republic of Congo Regulatory Authority, which was the main partner in the research.

Peptidome characterization of the antipyretic fraction of Bubali Cornu aqueous extract by nano liquid chromatography with orbitrap mass spectrometry detection.

In the present study, the antipyretic activity of Bubali Cornu (water buffalo horn) fraction and its metabolomics were investigated. The fraction decreased rat rectal temperature, and 13 endogenous metabolites were identified as potential biomarkers. Selected metabolites were involved in arachidonic acid metabolism and glycerophospholipid metabolism etc. Following treatment with the fraction, four metabolites, pyroglutamic acid, palmitelaidic acid, leukotriene A4, and prostaglandin A2 were reversed. In addition, the levels of interleukin-1ß, tumor necrosis factor-α, prostaglandin E2 , and cyclic adenosine monophosphate in plasma were also reversed after treatment as determined by enzyme linked immunosorbent assay. Furthermore, nano-flow liquid chromatography with orbitrap mass spectrometry detection was used to analyze the peptides in the fraction. In total, 824 peptide sequences mainly from keratins were determined, with Keratin 14, Keratin 34, and Keratin 86 representing the three main types of keratin hydrolysis in water buffalo horn based on peptide heat maps. Of the identified peptides, 81.2% were hydrophilic and the molecular weight of 70.3% of identified peptides was lower than 2000 Da. According to the metabolomics- and peptidomics-based approach used in the present study, it is feasible to identify and analyze the active peptide matrix from animal-horn-derived traditional Chinese medicines.

Available sustainable alternatives replace endangered animal horn based on their proteomic analysis and bio-effect evaluation.

The use of endangered animal products in traditional Chinese medicine (TCM) and other ethno-medicines is culturally widespread across many regions of Asia. In the present study, traditional efficacies of seven types of animal horn including antipyretic, sedative and procoagulant activities were evaluated. Shotgun proteomic analysis was performed on material from horns following separation into soluble and insoluble fractions. Over 200 proteins were identified in each sample using nano LC-MS/MS, and these were classified according to their molecular function and cellular component using principal component analysis (PCA). The results indicated that seven horns showed antipyretic, sedative and procoagulant effect. Proteomic analysis showed that YH and WBH were similar to RH in terms of protein profile, and GH was similar to SAH. In addition, YH and GH were similar to RH in their cellular component classification profile. PCA based on the composition of keratin and keratin-associated proteins showed that constituents of WBH and GH were similar to RH and SAH, respectively. This is the first analysis of the protein content of animal horns used in TCM, and it is effective to substitute the horn of endangered animals with sustainable alternatives from domestic animals.

Plasma metabolomics combined with lipidomics profiling reveals the potential antipyretic mechanisms of Qingkailing injection in a rat model.

Qingkailing injection (QKLI) has a notable antipyretic effect and is widely used in China as a clinical emergency medicine. To elucidate the pharmacological action thoroughly, following the investigation of the urine metabolome and hypothalamus metabolome, plasma metabolomics combined with lipidomics profiling of the QKLI antipyretic effect in a rat model is described in this paper. Compared with pure metabolomics profiling, this non-targeted plasma metabolomics combined with lipidomics profiling based on ultra-performance liquid chromatography-coupled with quadrupole time-of-flight mass spectrometry (UPLC Q-TOF/MS) could be used for a large-scale detection of features in plasma samples. The results showed that 15 metabolites at the 1 h time point and 19 metabolites at the 2 h time point after QKLI administration were associated with the antipyretic effect of QKLI, including amino acid, phosphatidylcholine and lysophosphatidylcholine. The metabolism pathway analysis revealed that the potential biomarkers, which were important for the antipyretic mechanism of QKLI, were closely responsible for correcting the perturbed pathways of amino acid metabolism and lipid metabolism. In conclusion, the use of complementary UPLC Q-TOF/MS based metabolomics and lipidomics allows for the discovery of new potential plasma biomarkers in the QKLI antipyretic process and the associated pathways, and aided in advancing the understanding of the holism and synergism of the Chinese drug.

Establishment of a standard reference material (SRM) herbal DNA barcode library of Vitex negundo L. (lagundi) for quality control measures.

The majority of the population in the Philippines relies on herbal products as their primary source for their healthcare needs. After the recognition of Vitex negundo L. (lagundi) as an important and effective alternative medicine for cough, sore throat, asthma and fever by the Philippine Department of Health (DOH), there was an increase in the production of lagundi-based herbal products in the form of teas, capsules and syrups. The efficiency of these products is greatly reliant on the use of authentic plant material, and to this day no standard protocol has been established to authenticate plant materials. DNA barcoding offers a quick and reliable species authentication tool, but its application to plant material has been less successful due to (1) lack of a standard DNA barcoding loci in plants and (2) poor DNA yield from powderised plant products. This study reports the successful application of DNA barcoding in the authentication of five V. negundo herbal products sold in the Philippines. Also, the first standard reference material (SRM) herbal library for the recognition of authentic V. negundo samples was established using 42 gene accessions of ITS, psbA-trnH and matK barcoding loci. Authentication of the herbal products utilised the SRM following the BLASTn and maximum-likelihood (ML) tree construction criterion. Barcode sequences were retrieved for ITS and psbA-trnH of all products tested and the results of the study revealed that only one out of five herbal products satisfied both BLASTn and ML criterion and was considered to contain authentic V. negundo. The results prompt the urgent need to utilise DNA barcoding in authenticating herbal products available in the Philippine market. Authentication of these products will secure consumer health by preventing the negative effects of adulteration, substitution and contamination.

Antipyretic, analgesic and anti-inflammatory effects of Kickxia ramosissima.

ETHNOPHARMACOLOGICAL RELEVANCE: Branched cancerwort, Kickxia ramosissima (Wall.) Janchen (Scrophulariaceae) is traditionally used for the treatment of inflammatory disorders such as rheumatism, diabetes, jaundice and for activation of immune system. Local communities also used this plant for the treatment of spleen enlargement, as febrifuge and in dysmenorrhea. In this investigation antipyretic, analgesic and anti-inflammatory effects of K. ramosissima have been evaluated. METHODS: Dried powder of the whole plant of K. ramosissima was extracted with methanol (KRM) and partitioned with solvents to obtain the n-hexane (KRH), chloroform (KRC), ethyl acetate (KRE), n-butanol (KRB) and the residual aqueous (KRA) fraction. KRM and the derived fractions were analyzed for the phytochemical constituents, yeast induced pyrexia, analgesic and anti-inflammatory activities by using carrageenan and Freunds' complete adjuvant-induced paw edema model in rat. On account of appreciable effects of KRM in the aforesaid models, KRM was subjected to the carrageenan induced air pouch model in rat. The exudate of air pouch was analyzed for the count of neutrophils, monocytes, lymphocytes and WBCs and for the estimation of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO) and prostaglandin (PGE2). RESULTS: Phytochemical investigation of KRM indicated the existence of tannins, flavonoids, alkaloids, coumarins, cardiac glycosides, saponins, terpenoids and phlobatannins. Maximum concentration of total phenolic was determined in KRB followed by KRM while reverse was true for total flavonoids contents. KRM (200mg/kg) distinctly decreased the rectal temperature in yeast induced pyrexia comparable to standard, paracetamol. Pain sensation was effectively inhibited at 200mg/kg p.o. of KRM and KRB as manifested by a decrease (P<0.001) in count of writhing induced with acetic acid and increase of latency time in hot plate. Anti-inflammatory effects of KRM were evident and edema formation induced with carrageenan and Freunds' complete adjuvant-induced paw edema in rat was significantly (P<0.001) inhibited. Count of neutrophils, monocytes, lymphocytes, and WBCs along with inflammatory mediators; IL-6, NO, TNF-α and PGE2 was significantly (P<0.001) decreased in subcutaneous air pouch exudate with KRM. HPLC analysis of KRM indicated the presence of gallic acid, caffeic acid, rutin, catechin and myricetin. CONCLUSION: The results suggested the anti-inflammatory effects of KRM in inflammation related disorders, might be attributed by the presence of active phytoconstituents; flavonoids, saponins and terpenoids.

Comparative evaluation of cariogenic and erosive potential of commonly prescribed pediatric liquid medicaments: an in vitro study.

INTRODUCTION: Liquid oral medicines being the most accepted form of medication in children are frequently prescribed. The harmful effects of these liquid medicaments on a child's dental health are not known to many. The present study aimed to evaluate and compare the cariogenic and erosive potential of 5 most commonly prescribed pediatric liquid medicaments (PLM) in Pimpri Chinchwad and Pune city, Pune district. MATERIALS AND METHODS: Most commonly prescribed PLM in Pune district were selected as opined by 50 pediatricians. The selected medicaments were Syr. Augmentin® Duo, Syr. Valparin®, Syr. Combiflam®, Syr. Visyneral and Syr. Orofer®. An estimation of pH, percentage of sucrose concentration and calcium dissolving capacity of these preparations was carried out. The results as obtained were subjected to statistical analysis using SPSS v 17.0 for windows. The statistical test as undertaken was Pearson's correlation coeffcient(r). RESULTS: Sucrose was seen to be present in Syr. Combiflam® (35.75% ± 0.25%) and Syr. Visyneral (18.48% ± 0.43%). Acidic pH was observed for Syr. Visyneral (mean pH 3.63 ± 0.04), Syr. Combiflam®(mean pH 5.03 ± 0.02) and Syr. Augmentin® (mean pH 6.22 ± 0.02). Highest calcium dissolution was seen with Syr. Combiflam®(295.86 mg/ml) and the least with Syr. Orofer® (25.51 mg/ml). No statistical significant correlation was observed with calcium dissolution potential of PLM in comparison with their respective pH. CONCLUSION: Syr. Combiflam® can be regarded as the highest cariogenic and erosive potential medicament among the compared and tested PLM. CLINICAL SIGNIFICANCE: Considering syrups with high cariogenic and erosive potential should always follow with proper oral hygiene practices or search for an alternative drugs void of such detrimental effects.

[Rapid identification 15 effective components of anti common cold medicine with MRM by LC-MS/MS].

This paper reports the establishment of a method for rapid identification 15 effective components of anti common cold medicine (paracetamol, aminophenazone, pseudoephedrine hydrochloride, methylephedrine hydrochloride, caffeine, amantadine hydrochloride, phenazone, guaifenesin, chlorphenamine maleate, dextromethorphen hydrobromide, diphenhydramine hydrochloride, promethazine hydrochloride, propyphenazone, benorilate and diclofenac sodium) with MRM by LC-MS/MS. The samples were extracted by methanol and were separated from a Altantis T3 column within 15 min with a gradient of acetonitrile-ammonium acetate (containing 0.25% glacial acetic acid), a tandem quadrupole mass spectrometer equipped with electrospray ionization source (ESI) was used in positive ion mode, and multiple reaction monitoring (MRM) was performed for qualitative analysis of these compounds. The minimum detectable quantity were 0.33-2.5 microg x kg(-1) of the 15 compounds. The method is simple, accurate and with good reproducibility for rapid identification many components in the same chromatographic condition, and provides a reference for qualitative analysis illegally added chemicals in anti common cold medicine.

Separation and electrochemical detection of paracetamol and 4-aminophenol in a paper-based microfluidic device.

The present work describes the construction and application of a simple, low cost and sensitive microfluidic paper-based device with electrochemical detection for the detection of paracetamol and 4-aminophenol. The separation channels of a width of 2.0 mm were created on paper using a wax printing process to define the regions of the device. A baseline separation level of the analytes can be obtained in 0.1 mol L(-1) acetate buffer solution at pH 4.5 and by injecting 500 nL of the standard solutions at 12 mm from the working electrode. The electrochemical detection system was created at the end of the channels through a process known as sputtering. The previously separated analytes were detected at the end of the hydrophilic separation channel by applying a potential of 400 mV vs. pseudo Au on the working electrode. Experimental variables such as type of paper (cation exchanger and n1), pH, sample volume, applied potential and distance of sample injection were evaluated and, under the conditions of higher response, it was possible to obtain detection limits of 25.0 and 10.0 µmol L(-1) for paracetamol and 4-aminophenol, respectively.

The breakage behaviour of Aspirin under quasi-static indentation and single particle impact loading: effect of crystallographic anisotropy.

The influence of crystallographic structural anisotropy on the breakage behaviour of Aspirin under impact loading is highlighted. Under both quasi-static testing conditions, using nano-indentation, and dynamic impact tests, Aspirin demonstrates clear anisotropy in its slip and fracture behaviour. During nano-indentation on the (100) and (001) faces, cracks were propagated along the [010] direction. While the hardness was found to be comparatively similar for both these faces, it was observed that slip due to plastic deformation occurred more readily on the (100) than the (001) crystal planes suggesting the former as the preferred slip plane. Furthermore, the fracture toughness on the (001) planes was found to be distinctly lower than that of the (100) planes, indicating the former as the preferred cleavage plane. Observations of the crystal morphology of damaged particles after dynamic impact testing showed that both the chipping and fragmentation of Aspirin mostly occurred via cleavage in a manner consistent with the observed fracture behaviour following nano-indentation. This work highlights the importance of cleavage as a dominant factor underpinning the fracture mechanism of Aspirin under both quasi-static and impact loading conditions.

Analysis of active components of rhinoceros, water buffalo and yak horns using two-dimensional electrophoresis and ethnopharmacological evaluation.

Cornu Rhinoceri Asiatici (rhinoceros horn, RH), Cornu Bubali (water buffalo horn, WBH), and Cornu Bovis grunniens (yak horn, YH) are traditional Chinese medicine (TCM), and have been used in China for thousands of years. In this study, ethnopharmacological experiments were used to evaluate and verify the traditional efficacies of horns. Area under curve (AUC) was used to quantify the pharmacological efficacy strength of three horns. Two-dimensional electrophoresis (2-DE) was used to analyze the protein components in horns, as a result, 14 common protein spots in rhinoceros horn, water buffalo horn, and yak horn electrophoresis gels were found by image analysis. Then linear regression analysis was used to establish the correlation between pharmacological efficacies and components in the horns, and five potential active components were selected from the 14 common protein spots. Finally, two protein spots from five were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). In this study, a simple method to construct correlation between components and efficacy strength was explored by linear regression analysis, which could be applied to screen potential active components of animal horns.

Analysis of the presence of cardiovascular and analgesic/anti-inflammatory/antipyretic pharmaceuticals in river- and drinking-water of the Madrid Region in Spain.

Interest in the presence of pharmaceuticals in wastewater, in the water of our rivers and, to a lesser extent, in our drinking water, has been growing in recent decades. Many of these substances, currently classified as "emerging pollutants", are biologically active compounds and continuously released in effluents. As sewage treatment plants (STPs) are not adequately equipped to eliminate all of these substances completely, some are discharged directly into rivers. In Spain, as in most of its neighbouring countries, there is an elevated use of pharmaceuticals for the treatment of cardiovascular diseases (which are extremely prevalent among the older adult population) and anti-inflammatory medications, which are obtainable over the counter without a medical prescription. This study therefore sought to determine to what degree pharmaceuticals with the highest regional prescription and/or use rates, such as cardiovascular and analgesic/anti-inflammatory/antipyretic medications, were present in the principal rivers (Jarama, Manzanares, Guadarrama, Henares and Tagus) and tap-water samples of the Madrid Region (MR). Samples were taken downstream the discharge of 10 of the most important region's STPs and the most frequently used drugs in the region were analysed for. Of the 24 drugs analysed, 21 were detected at concentrations ranging from 2 ng L⁻¹ to 18 µg L⁻¹. The highest drug concentrations corresponded to ibuprofen, diclofenac, naproxen, atenolol, frusemide (furosemide), gemfibrozil and hydrochlorthiazide, and in most cases exceeded the amounts reported in the scientific literature. No traces of these groups of pharmaceuticals were detected in the drinking water analysed. On the basis of the high concentrations detected, we believe that an environmental surveillance system should be implemented to assess the continuous discharge of these pharmaceuticals and their possible ecotoxicological effects. At the same time, efforts to raise the awareness of the public about responsible use and the proper disposal of such substances at purpose-designated collection points should be increased. Furthermore sewage treatment processes should be suitably adapted to increase the rates of removal of these drugs.

[Electrochemical sensor for acetaminophen based on layer-by-layer self assembly technique].

A novel type of carbon nanotube-coated Au nanoparticle and [bmim]BF4 composite modified glassy carbon electrode was fabricated by a layer-by-layer self-assembly technique. The electrochemical performance of acetaminophen (ACOP) on the modified electrode was investigated by cyclic voltammetry. The Nafion/GNPs/RTIL/MWNTs/GC electrode showed an excellent electrocatalytic activity for the oxidation of ACOP and accelerated electron transfer between the electrode and ACOP. For ACOP, the reversible electrochemical process was observed on the Nafion/GNPs/RTIL/MWNTs/GC electrode, while irreversible electrochemical process occurred on the GC electrode. For the Nafion/GNPs/RTIL/MWNTs/GC electrode, the anodic peak potential of ACOP was moved from 0.562 V to 0.413 V, with a potential drop of 149 mV. At the same time, the reduction peak potential was 0.384 V, and the potential difference was only 29 mV. It was shown that the modified electrode possessed higher electrocatalytic activity and more sensitive effect for the detection of ACOP than both MWNTs/GC electrode and GC electrode. The effects of the different experimental conditions on the electrochemical behaviors of ACOP were explored. Under the optimum conditions of preparation and experimental, the linear calibration curves of ACOP were obtained in a wide range of 2 x 10(-1) to 4.0 x 10(-4) mol x L(-1) with a correlation coefficient 0.999 2 and a detection limit of 2.6 x 10(-8) mol x L(-1) (the ratio of signal to noise, 3:1). The recovery rate was 97.9%-100.8%. This method can be used to determine ACOP in paracetamol tablets with satisfactory results.