Comprehensive quality evaluation of Guge fengtong tablets / 中国药房

OBJECTIVE To establish a method for the content determination of 11 components such as protodioscin in Guge fengtong tablets， and to evaluate the comprehensive quality of Guge fengtong tablets by combining with chemometric analysis and entropy weight-technique for order preference by similarity to ideal solution （EW-TOPSIS） method. METHODS HPLC method was adopted. The determination was performed on Agilent Eclipse Plus C18 column with a mobile phase consisted of acetonitrile- 0.2% phosphoric acid solution at the flow rate of 1.0 mL/min by gradient elution. The column temperature was set at 30 ℃ . The detection wavelengths were set at 203 nm （0-28 min， protodioscin， methyl protodioscin， pseudoprotodioscin， dioscin） and 280 nm （28-60 min， catechin， epicatechin， liquiritigenin， medicarpin， 6-gingerol， 8-gingerol， 10-gingerol）； the sample size was 10 μL. Using epicatechin as the internal reference， quantitative analysis of multi-components by single marker （QAMS） method was used to determine the contents of protodioscin， methyl protodioscin， pseudoprotodioscin， dioscin， catechin， liquiritigenin， medicarpin， 6-gingerol， 8-gingerol and 10-gingerol， which were compared with the results of the external standard method. SPSS 26.0 software and SIMCA 14.1 software were used for principal component analysis and orthogonal partial least squares-discriminant analysis， with variable importance in projection （VIP） value greater than 1 as the standard， to screen for differential markers that affect the quality； the EW-TOPSIS method was adopted to evaluate the quality of 15 batches of samples comprehensively.RESULTS The contents of protodioscin， methyl protodioscin， pseudoprotodioscin， dioscin， catechin， liquiritigenin， medi-carpin， 6-gingerol， 8-gingerol and 10-gingerol determined by HPLC combined with QAMS were 6.330-10.863， 1.150-2.274， 0.431- 0.740， 2.818-4.823， 0.826-1.510， 0.043-0.094， 0.079-0.231， 0.479-1.020， 0.146-0.288， 0.118-0.318 mg/g， respectively； there were no statistical significances， compared with the external standard method （P＞0.05）. A total of 15 batches of samples were clustered into 3 groups， with S1-S6， S7-S10， and S11-S15 clustered into one group， respectively. The VIP values of protodioscin， epicatechin， dioscin and 6-gingerol were greater than 1. Euclidean closeness values of the optimal solution （C）i for 15 batches of samples were 0.163 5 to 0.703 7， and Ci values of S11-S15 were all higher than 0.6. CONCLUSIONS The established QAMS method is accurate and simple， and can be used for comprehensive quality evaluation of Guge fengtong tablets， by combining with chemometric analysis and EW-TOPSIS method. Protodioscin， epicatechin， dioscin and 6-gingerol are the differential markers that affect the quality of Guge fengtong tablets. Samples S11-S15 have better quality.

Optimization of processing methods for Terminalia chebula based on fingerprint，antioxidant spectrum-effect correlation and multi-component contents / 中国药房

OBJECTIVE To compare the similarities and differences between raw and different preparations of Terminalia chebula based on fingerprint， antioxidant spectrum-effect correlation and multi-component contents， and to provide a reference for searching for modern processing methods of T. chebula that are similar to classical ancient methods. METHODS Ten batches of raw and different preparations of T. chebula （single stir-fried products， bran-roasted products， sand-scorched products， ash-roasted products， stir-fried charcoal products， and wine-steamed products） were used as test samples. The high-performance liquid chromatography （HPLC） fingerprints of different samples were established by using the Similarity Evaluation System for Chromatographic Fingerprint of TCM （2012 edition）， the chromatographic peaks were identified， and chemometrics analysis was carried out. At the same time， HPLC method was used to determine the contents of 8 identified components. The antioxidant capacity of raw and different preparations of T. chebula was determined by DPPH free radical scavenging method， and the spectrum- effect relationship was analyzed. RESULTS A total of 20 common peaks were identified in the fingerprints of the raw and different preparations of T. chebula， and the similarity of each sample was ＞0.9. Nine common peaks were identified from the raw and different preparations of T. chebula， including chromatographic peak 2 （chebulic acid）， 3 （gallic acid）， 6 （punicalagin A）， 8 （punicalagin B）， 12 （corilagin）， 15 （chebulagic acid）， 18 （ellagic acid）， 19 （1，2，3，4，6-O-pentagalloyl glucose）， 20 （chebulinic acid）， etc. Compared with crude drug， the contents of the above 8 components （punicalagin A and B are recorded as punicalagin） in different preparations of T. chebula were changed， and the changes of the contents of the stir-fried charcoal and wine-steamed products were more obvious than those of other processed products. Chemometric analysis showed that the fingerprints of stir-fried charcoal and wine-steamed products of T. chebula were obviously distinguished from other processed products， and the fingerprint information of raw products and other processed products of T. chebula was partially overlapped. Four main differential components （chebulinic acid， chebulagic acid， gallic acid， ellagic acid） were obtained between raw and processed products of T. chebula； and four main effective components （chebulinic acid， chebulagic acid， gallic acid， corilagin） were obtained by analyzing the spectrum-effect relationship of antioxidant activity. The single stir-fried product of T. chebula showed the strongest antioxidant activity. CONCLUSIONS The single stir-frying method is a modern processing method of T. chebula which is similar to the classical ancient method and is more excellent.

Quality evaluation of Qilong Zhuang'er oral liquid based on UHPLC-Q-exactive orbitrap MS and chemometrics analysis / 药学学报

An UHPLC-Q-exactive orbitrap MS method for the simultaneous determination of 19 chemical components in Qilong Zhuang'er oral liquid was established and the quality differences between different batches of samples was compared by chemometric analysis to provide a basis for the quality evaluation of the preparation. The contents of allantoin, L-proline, pyroglutamic acid, hordenine, adenosine, L-phenylalanine, guanosine, L-tryptophan, caffeic acid, calycosin-7-glucoside, verbascoside, isoacteoside, ononin, calycosin, 3-hydroxy-9,10-dimethoxyptercarpan, formononetin, atractylenolide III, atractylenolide II and astragaloside A were analyzed by cluster heat map, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) using Hiplot platform and MarkerlynxXS software to comprehensively evaluate the quality difference of different batches of Qilong Zhuang'er oral liquid. The 19 chemical compounds showed good linearity in their respective concentration ranges (r ≥ 0.999). The RSD of precision, repeatability and stability (24 h) tests were all less than 1.94%. The average recovery was 97.24%-102.75% (RSD < 2.74%, n = 6). The 10 batches of samples were divided into two categories by cluster heat map and PCA analysis. 3-Hydroxy-9,10-dimethoxyptercarpan, atractylenolide III, calycosin, atractylenolide II, formononetin, allantoin and caffeic acid were identified as differential markers by PLS-DA. The established multi component quantitative method of Qilong Zhuang'er oral liquid combined with chemometric analysis can provide reference for the quality evaluation of the preparation.

Content determination and chemometric analysis of 11 components in Xueli zhike syrup / 中国药房

OBJECTIVE To determine the contents of 11 components in Xueli zhike syrup， establish its chemometric method and provide reference for its quality control. METHODS HPLC method was established to simultaneously determine the contents of amygdalin， deapi-platycoside E， platycoside E， platycodin D3， euscaphic acid， tormentic acid， maslinic acid， corosolic acid， praeruptorin A， praeruptorin B and praeruptorin E in 12 batches of Xueli zhike syrup. The quality evaluation of 12 batches of samples was performed by chemometrics. RESULTS The 11 components had good linear relationships within their respective ranges （r≥0.999 1）； RSDs of precision， reproducibility and stability （24 h） tests were all lower than 2.00%. The average recovery rates ranged 96.90%-100.01% （RSDs were all lower than 2.00%）. Cluster analysis showed that 12 batches of samples were clustered into 3 groups. Principal component analysis showed that the first two principal components could represent 88.53% information of 11 components in Xueli zhike syrup. Partial least squares-discrimination analysis showed that euscaphic acid， amygdalin and praeruptorin A were the main potential markers affecting the quality of Xueli zhike syrup. CONCLUSIONS The established method can be used to control the quality of Xueli zhike syrup.

Establishment and Analysis of the Fingerprints of Adiantum capillusveneris from Different Producing Areas and Content Determination of Its Differential Components / 中国药房

OBJECTIVE：To establish the fingerprint of Adiantum capillusveneris from different producing areas ，and to conduct chemometric analysis and content determination of differential components ，so as to provide reference for quality control of A. capillusveneris . METHODS ：HPLC-DAD combined with Similarity Evaluation System of TCM Chromatogramtic Fingerprint （2004 A edition ）were used to establish fingerprint of 19 batches of A. capillusveneris from different producing areas （S1-S19）. Common peaks were confirmed and their similarities were evaluated. Chemometric analysis methods such as cluster analysis ， principle component analysis （PCA），orthogonal partial least squares discriminant analysis （OPLS-DA）were used to evaluate the quality of 19 batches of A. capillusveneris from different producing areas ，screen the differential components ，and determine the contents of some differential components. RESULTS ：Among 19 batches of A. capillusveneris from different producing areas ，22 common peaks were confirmed ；peak 9 was chlorogenic acid ，peak 17 was quercetin- 3-O-β-D-glucopyranoside，peak 20 was kaempferol-3-O-rutoside；the similarity of 19 batches of sample were 0.677-0.962. Through cluster analysis ，it was found that S 7 and S 10 were clustered into one category ；S15 and S 18 were clustered into one category ；and S 1-S6，S8，S9，S11-S14，S16，S17 and S 19 were clustered into one category. PCA and OPLS-DA found that S 7 and S 10 were clustered into one category ；S15 were clustered into one category ；S18 were clustered into one category ；S1-S6，S8，S9，S11-S14，S16，S17 and S 19 were clustered into one category. Chlorogenic acid ，quercetin-3-O-β-D-glucopyranoside，kaempferol-3-O-rutoside and chemical composition represented by peak 14 were the differential components of the〔2017〕2841）； medicinal material. Among 19 batches of A. capillusveneris ， average contents of chlorogenic acid and quercetin- 3-O-β-D- glucopyranoside and kaempferol- 3-O-rutoside were 0.10-4.25， 0.31-7.11，0.61-12.00 mg/g，respectively. CONCLUSIONS ： 电话：0851-86614212。 HPLC-DAD fingerprints of A. capillusveneris from different producing areas are establishe d in the study ，and three common peaks are identified. Four differential components affecting the quality of A. capillusveneris are screened ， and the contents of chlorogenic acid ， quercetin-3-O-β-D-glucopyranoside and kaempferol-3-O-rutoside in A. capillusveneris from different producing areas were significantly different.

Rapid identification of microbial contaminants in pharmaceutical products using a PCA/LDA-based FTIR-ATR method

Microbiological quality of pharmaceuticals is fundamental in ensuring efficacy and safety of medicines. Conventional methods for microbial identification in non-sterile drugs are widely used; however they can be time-consuming and laborious. The aim of this paper was to develop a chemometric-based rapid microbiological method (RMM) for identifying contaminants in pharmaceutical products using Fourier transform infrared with attenuated total reflectance spectrometry (FTIR-ATR). Principal components analysis (PCA) and linear discriminant analysis (LDA) were used to obtain a predictive model capable of distinguishing Bacillus subtilis (ATCC 6633), Candida albicans (ATCC 10231), Enterococcus faecium (ATCC 8459), Escherichia coli (ATCC 8739), Micrococcus luteus (ATCC 10240), Pseudomonas aeruginosa (ATCC 9027), Salmonella typhimurium (ATCC 14028), Staphylococcus aureus (ATCC 6538), and Staphylococcus epidermidis (ATCC 12228) microbial growth. FTIR-ATR spectra provide data on proteins, DNA/RNA, lipids, and carbohydrates constitution of microbial growth. Microbial identification provided by PCA/LDA based on FTIR-ATR method were compatible with those obtained using traditional microbiological methods. The chemometric-based FTIR-ATR method for rapid identification of microbial contaminants in pharmaceutical products was validated by assessing the sensitivity (93.5%), specificity (83.3%), and limit of detection (17-23 CFU/mL of sample). Therefore, we propose that FTIR-ATR spectroscopy may be used for rapid identification of microbial contaminants in pharmaceutical products and taking into account the samples studied

How to identify “Material basis–Quality markers” more accurately in Chinese herbal medicines from modern chromatography-mass spectrometry data-sets: Opportunities and challenges of chemometric tools / 中草药·英文版

Modern chromatography - mass spectrometer (MS) technology is an essential weapon in the exploration of traditional Chinese medicines (TCMs) which is based on the “effectiveness-material basis-quality markers (Q-markers)”. Nevertheless, the hardware bottleneck and irregular operation will limit the accuracy and comprehensiveness of test results. Chemometrics was thereby used to solve the existing problems: 1) The method of ‘design-modeling-optimization’ can be adopted to solve the multi-factor and multi-level problems in sample preparation/ parameter setting; 2) The approaches of signal processing can be used to calibrate the deviation from retention time (rt) dimension and mass-to-charge ratio (m/z) dimension in different types of instruments; 3) The methods of multivariate calibration and multivariate resolution can be utilized to analyze the co-eluting peaks in complex samples. When the researchers need to capture essential information on raw data sets extracting the higher level of information on essential features, 1) The significant components which affects the drug properties/efficacy can be find by the pattern recognition and variable selection; 2) Fingerprint-efficacy modeling is explored to clarify the material basis, or to screen out the Q-markers of biological significance; 3) Chemometric tools can apply to integrate chemical (metabolic) fingerprints with network pharmacology, bioinformatics, omics and others from a multi-level perspective. Under these programs, the qualitative/quantitative works will achieve in chemical (metabolic) fingerprint and metabolic trajectories, which leads to an accurate reflection of “material basis and Q-markers” in TCMs. Likewise, an in-depth hidden information can be disclosed, so that the components of drug properties/efficacy will be found. More importantly, multidimensional data can be integrated with fingerprints to acquire more hidden information.

Rp-Hplc And Chemometric Methods For The Determination Of Two Anti-Diabetic Mixtures; Metformin Hydrochloride-Canagliflozin And Metformin Hydrochloride-Gliclazide In Their Pharmaceutical Formulation

Objective: To develop and validate novel more sensitive analytical methods for the concurrent quantification of metformin-canagliflozin and metformin-gliclazide in their bulk forms and in their pharmaceutical preparations. Methods: Two methods were developed based on several chemometric assisted spectrophotometric methods and a Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC). The first method applies different spectrophotometric chemometric assisted methods, including ratio difference, derivative ratio and extended ratio subtraction method, while the second method describes a RP-HPLC separation of metformin hydrochloride-canagliflozin and metformin hydrochloride-gliclazide binary mixtures using a C18 column with a mobile phase consisting of acetonitrile: potassium dihydrogen phosphate (adjusted to pH 3) with sodium lauryl sulphate as additive in the ratio of 30:70 (%v/v) in isocratic elution mode at 1 ml/min. Results: The proposed methods were able to quantify each of the studied drugs in their binary mixtures with high percentage recoveries in both methods. The spectrophotometric methods were able to quantify each of metformin, canagliflozin and gliclazide in the ranges of 2.0-20.0 μg/ml, 1.5-40.0 μg/ml and 2.0-30.0 μg/ml, respectively. The RP-HPLC method produced well-resolved peaks at a retention time of 3.92, 6.92 and 9.10 min in the concentration ranges of 50.0-300.0 μg/ml, 5.0-50.0 μg/ml and 10.0-100.0 μg/ml for metformin, canagliflozin and gliclazide, respectively. The proposed methods were optimized and validated in accordance to the International Conference of Harmonisation (ICH) guidelines in terms of linearity, LOD, LOQ, precision and accuracy. Conclusion: The developed methods were found to be sensitive and reproducible methods for the simultaneous determination of anti-diabetic binary mixtures; metformin hydrochloride-canagliflozin and metformin hydrochloride-gliclazide. And thus were successfully employed for the quality control analysis of the pharmaceutical formulations of the studied binary mixtures.

Quality Evaluation of Glycyrrhiza uralensis Fisch. in Different Harvest Periods Based on Combinative Methods of HPLC Specific Chromatogram, Multi-Component Assay, and Chemometrics / 中国药学杂志

OBJECTIVEP: To evaluate comprehensively the quality of Glycyrrhiza uralensis Fisch. in different harvest periods by chemometric analysis based on the HPLC specific chromatogram and multi-component assay. METHODS: The similarity was analyzed with "Similarity Evaluation System for Chromatographic Fingerprint of Chinese Materia Medica 2012". t-test, correlation analysis, clustering analysis(HCA), principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were used for data analysis. RESULTS: Twenty-one peaks were selected as common peaks of the fingerprint. The similarity of the samples were above 0.9. The contents of liquiritin, glycyrrhizic acid, liquiritin apioside, isoliquiritin apioside, isoliquiritin, neoisoliquiritin, echinatin, and liquiritigenin were determined.There were some differences in the quality of Glycyrrhiza uralensis Fisch. in different harvest periods, with liquiritin apioside, neoisoliquiritin and echinatin as the main compounds of difference. CONCLUSION: Autumn is confirmed as the best harvesting period of Glycyrrhiza uralensis Fisch. by chemometric analysis. It is suggested that liquiritin apioside should be used as the key quality control indicator for evaluating Glycyrrhiza uralensis Fisch.in different harvest periods.

Qualitative and quantitative analysis of characteristic chemical constituents in wine-processed Corni Fructus by chemometric and UPLC-PDA / 中草药

Objective: To screen the differential ingredients between crude and wine-processed Corni Fructus and determin their content. Methods: An integrated strategy using ultra performance liquid chromatography coupled with tandem quadrupole time-of- flight mass spectrometry (UPLC-Q-TOF/MS) and the chemometric approach was applied to compare the global chemical profile of crude and wine-processed Corni Fructus. Then, the main differential ingredients were quantified by UPLC-PDA. Results: The chemical profiling of wine-processed Corni Fructus was significantly different. Ten compounds could be considered as characteristic chemical markers for distinguishing crude and wine-processed Corni Fructus, including 5-hydroxymethyl furfuraldehyde (5-HMF), gallic acid, protocatechuic acid, morroniside, loganic acid, sweroside, cornin, dihydroquercetin, loganin and cornoside. A new UPLC-PDA quantitative method for analyzing simultaneously the above ten compounds in wine-processed Corni Fructus was established. The results of methodology investigation showed that the ten components were well linear within the investigation range (r ≥ 0.999 7). Compared with the crude Corni Fructus, the content of seven components were increased, including gallic acid, 5-HMF, loganin, morroniside, cornin, sweroside and dihydroquercetin, and the other three components in wine-processed Corni Fructus were decreased. Conclusion: The differential ingredients obtained by chemometric-based approach can be used to distinguish crude and wine-processed Corni Fructus. The determination method of wine-processed Corni Fructus established is accurate and reliable, which can be used for the quality control of Corni Fructus.

Chemometric-assisted RP-HPLC method for the simultaneous determination of ambroxol hydrochloride, terbutaline sulfate, and guaiphenesin in combined dosage form

An isocratic reverse-phase High performance liquid chromatography (HPLC) method using a chemometric modelwas developed and validated for the simultaneous determination of ambroxol hydrochloride, terbutaline sulfate,and guaiphenesin in their combined dosage form. Central composite design which is a subset of response surfacemethodology was used as the chemometric model. The separation of three drugs was carried out by using a PhenomenexC18 column and detection at 220 nm using a UV detector. Based on initial trials, the three factors selected for thedesign were methanol (MN) concentration, mobile phase pH, and flow rate in the range of 55%–65% (v/v), 4–5 units,and 0.6–1 ml/min, respectively. The impact of the selected factors on the responses like retention time of first peak(tR1), resolution of 2nd and 3rd peak (Rs2,3), and theoretical plates of the first peak (TP1) were evaluated. Derringers’desirability function was used to optimize the responses. The conditions which were optimized for the assay of drugswere MN, ACN, and 50 mM KH2PO4 (pH 5) in the ratio of 55:10:35 at a flow rate of 0.8 ml/minute. The developedand optimized method was validated as per the International conference on harmonization (ICH) guidelines and canbe used for routine analysis in quality control laboratories.

Chemical characterization of two morphologically related Espeletia (Asteraceae) species and chemometric analysis based on essential oil components

ABSTRACT In this study, a comprehensive phytochemical characterization of two morphologically related species from the genus Espeletia Mutis ex Bonpl., namely, Espeletia grandiflora Humb. & Bonpl. and Espeletia killipii Cuatrec., Asteraceae, has been performed by gas chromatography coupled to flame ionization detection, gas chromatography coupled to mass spectrometry and ultra-high performance liquid chromatography coupled to ultraviolet and high-resolution mass spectrometry. Analysis of ethanol extracts (70%, v/v) from leaves and concomitant compound dereplication allowed the identification of major peaks, most of them new reports for the genus Espeletia or the subtribe Espeletiinae. Chemical characterization of resins essential oils indicated several similarities and differences between both species and from other members of the subtribe. Chemometric analysis (hierarchical clustering analysis and orthogonal partial least-squares discriminant analysis) applied to the essential oil composition of 31 species from Espeletiinae furthermore allowed the identification of three primary clusters correlated with the taxonomy. Hence, this study underscored qualitative and semiquantitative differences between the chemical composition of leaves and resins of E. grandiflora and E. killipii, provided information on chemotaxonomy and described the presence of different trends in the essential oil composition from species of Espeletiinae.

Multi-elemental analysis of Ziziphora clinopodioidesfrom different regions, periods and parts using atomic absorption spectrometry and chemometric approaches

ABSTRACTIn this study, ten trace elements in Ziziphora clinopodioidesLam., Lamiaceae, from different regions, periods and parts in Xinjiang were determined by atomic absorption spectrometry following microwave-assisted acid digestion. The decreasing sequence of elements levels was K > Ca > Mg > Fe > Cu > Zn > Na > Mn > Cd > Pb. Chemometric approaches, such as correlation analysis, principal component analysis, and hierarchical cluster analysis were applied to classify Z. clinopodioides according to its elements contents. Principal component analysis revealed 83.51% of the variance with the first four principal component variables. Hierarchical cluster analysis indicated five groups from the eighteen regions, and the result of classification can correspond to the geographical distribution for the most regions. Variation in the elements exhibited a decreasing trend, but of different types in the studied periods. Elemental contents distributed in leaves were higher than those in flowers and stems. Therefore, chemometric approaches could be used to analyze data to accurately classify Z. clinopodioides according to origins. This study provided some elemental information on chemotaxonomy, diversity, changing pattern, distribution, and metabolism of Z. clinopodioides at spatial and temporal levels, and could be used as a reference of planting and quality standards.

Comparative Study of Several Pattern Recognition Methods in the Identification of Volatile Oils of Tradition-al Chinese Medicine by Infrared Spectroscopy / 中国药房

OBJECTIVE:To compare the performance of several pattern recognition methods in the identification of volatile oils of traditional Chinese medicine(TCM)by infrared spectroscopy. METHODS:The volatile oils of several Lonicera and Citrus TCM were determined by infrared spectroscopy. All samples of infrared spectrum were classified by hierarchical clustering,K-mean clustering,artificial neural networks,and support vector machine. RESULTS:The results of hierarchical clustering and K-mean clus-tering were ineffective. Methods of artificial neural networks and support vector machine achieved correct classification rate of 100%. CONCLUSIONS:Artificial neural networks and support vector machine can be combined with infrared spectroscopy to cre-ate chemometric fingerprinting for the identification of volatile oils of TCM.

QSAR Rationale of Matrix Metalloproteinase Inhibition Activity in a Class of Carboxylic Acid Based Compounds.

The matrix metalloproteinase-13 (MMP-13) inhibitory activities of carboxylic acid based compounds, in presence and absence of bovine serum albumin (BSA), have been analyzed quantitatively in terms of chemometric descriptors. The statistically validated quantitative structure-activity relationship (QSAR) models obtained through combinatorial protocol in multiple linear regression (CP-MLR) analysis and the participated descriptors in these models provided rationales to explain the inhibitory activities of these congeners. For MMP-13 inhibition activity, the identified descriptors (BEHm1, BELm1 and BEHm8) have highlighted the role of the atomic mass in terms of the highest and lowest eigenvalues derived from Burden matrix. The positive correlation with activity suggested that their higher values are desirable in improving the activity of a compound. Additionally, the descriptor C-027 representing R-CH-X type fragment in a molecular structure advocates the absence of such type of fragment for the improved activity. On the other hand presence of RCO-N< or >N-X=X type fragment (descriptor N-072) would be beneficiary to the MMP-13 inhibitory activity. The structural features, rationalized by the descriptors MSD (Balaban’s mean square distance index), nCrHR (number of ring tertiary C (sp3), H-047 (H attached to C1(sp3)/C0(sp2)) and H-050 (H attached to heteroatom) have imparted positive impact on the MMP-13 w/BSA inhibition activity. The atomic properties such as atomic polarizability and atomic Sanderson’s electronegativity have shown their positive impact on the activity via descriptors BELp4 and GATS3e in respective eigenvalues or lag. The other descriptors, MATS1m and MATS3e, have revealed the negative influence of atomic mass and electronegativity on the of MMP-13 w/BSA inhibition activity. The results obtained from CP-MLR analysis have been supported further through partial least-squares (PLS) study.

Health Risks to Children and Adults Residing in Riverine Environments where Surficial Sediments Contain Metals Generated by Active Gold Mining in Ghana

The purpose of this study was to investigate the current status of metal pollution in the sediment from rivers, lakes, and streams in active gold mining districts in Ghana. Two hundred and fifty surface sediment samples from 99 locations were collected and analyzed for concentrations of As, Hg, Cr, Co, Cu, Fe, Zn, Pb, Cd, Ni, and Mn using inductively coupled plasma-mass spectroscopy (ICP-MS). Metal concentrations were then used to assess the human health risks to resident children and adults in central tendency exposure (CTE) and reasonable maximum exposure (RME) scenarios. The concentrations of Pb, Cd, and As were almost twice the threshold values established by the Hong Kong Interim Sediment Quality Guidelines (ISQG). Hg, Cu, and Cr concentrations in sediment were 14, 20, and 26 times higher than the Canadian Freshwater Sediment Guidelines for these elements. Also, the concentrations of Pb, Cu, Cr, and Hg were 3, 11, 12, and 16 times more than the Australian and New Zealand Environment and Conservation Council (ANZECC) sediment guideline values. The results of the human health risk assessment indicate that for ingestion of sediment under the central tendency exposure (CTE) scenario, the cancer risks for child and adult residents from exposure to As were 4.18 x 10(-6) and 1.84 x 10(-7), respectively. This suggests that up to 4 children out of one million equally exposed children would contract cancer if exposed continuously to As over 70 years (the assumed lifetime). The hazard index for child residents following exposure to Cr(VI) in the RME scenario was 4.2. This is greater than the United States Environmental Protection Agency (USEPA) threshold of 1, indicating that adverse health effects to children from exposure to Cr(VI) are possible. This study demonstrates the urgent need to control industrial emissions and the severe heavy metal pollution in gold mining environments.

Development and validation of a robust QSAR model for prediction of carcinogenicity of drugs.

Carcinogenicity is one of the toxicological endpoints causing the highest concern. Also, the standard bioassays in rodents used to assess the carcinogenic potential of chemicals and drugs are extremely long, costly and require the sacrifice of large numbers of animals. For these reasons, we have attempted development of a global quantitative structure–activity relationship (QSAR) model using a data set of 1464 compounds (the Galvez data set available from http://www.uv.es/~galvez/tablevi.pdf), including many marketed drugs for their carcinogenesis potential. Though experimental toxicity testing using animal models is unavoidable for new drug candidates at an advanced stage of drug development, yet the developed global QSAR model can in silico predict the carcinogenicity of new drug compounds to provide a tool for initial screening of new drug candidate molecules with reduced number of animal testing, money and time. Considering large number of data points with diverse structural features used for model development (ntraining = 732) and model validation (ntest = 732), the model developed in this study has an encouraging statistical quality (leave-one-out Q2 = 0.731, R2pred = 0.716). Our developed model suggests that higher lipophilicity values and conjugated ring systems, thioketo and nitro groups contribute positively towards drug carcinogenicity. On the contrary, tertiary and secondary nitrogens, phenolic, enolic and carboxylic OH fragments and presence of three-membered rings reduce the carcinogenicity. Branching, size and shape are found to be crucial factors for drug-induced carcinogenicity. One may consider all these points to reduce carcinogenic potential of the molecules.

Multivariate analysis of the effects of soil parameters and environmental factors on the flavonoid content of leaves of Passiflora incarnata L., Passifloraceae / Análise multivariada dos efeitos dos parâmetros do solo e fatores ambientais no teor de flavonoides das folhas de Passiflora incarnata L., Passifloraceae

The aim of the present study was to evaluate the effect of soil characteristics (pH, macro- and micro-nutrients), environmental factors (temperature, humidity, period of the year and time of day of collection) and meteorological conditions (rain, sun, cloud and cloud/rain) on the flavonoid content of leaves of Passiflora incarnata L., Passifloraceae. The total flavonoid contents of leaf samples harvested from plants cultivated or collected under different conditions were quantified by high-performance liquid chromatography with ultraviolet detection (HPLC-UV/PAD). Chemometric treatment of the data by principal component (PCA) and hierarchic cluster analyses (HCA) showed that the samples did not present a specific classification in relation to the environmental and soil variables studied, and that the environmental variables were not significant in describing the data set. However, the levels of the elements Fe, B and Cu present in the soil showed an inverse correlation with the total flavonoid contents of the leaves of P. incarnata.

O objetivo deste trabalho foi avaliar os efeitos do solo (pH, macro e micronutrientes), fatores ambientais (temperatura, umidade, época do ano e período da coleta) e condições meteorológicas (chuva, sol, nublado, nublado com chuva) no teor de flavonoides das folhas de Passiflora incarnata L. (Passifloraceae), através do tratamento quimiométrico dos dados por PCA (análise de componentes principais) e HCA (análise hierárquica de agrupamentos). Os flavonoides totais foram quantificados por cromatografia líquida de alta eficiência-detecção por ultravioleta (CLAE-UV/DAD). As análises por PCA e HCA mostraram que as amostras de Passiflora não apresentam uma classificação específica em relação às variáveis estudadas e que as variáveis do meio ambiente não são relevantes para descrever o modelo estudado, porém os elementos do solo Fe, B e Cu demonstraram correlação inversa à concentração dos flavonoides totais.