Simple and highly predictive QSAR method: application to a series of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-methoxybenzamides

A simple quantitative structure-activity relationship (QSAR) method of analysis used to predict biological activity for congeneric series of compounds is reported. This method is based on the application of bilinear or multilinear partial least squares regression to a data set, which is a binary matrix representing the substituents of a framework. It is appraised here to a series of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-methoxybenzamides, compounds with affinity towards the dopamine D₂ receptor subtype and showed high predictive ability, even when compared to a refined three-dimensional (3D) approach.     

Determination of biphenyl in the presence of polyphenyls : Water solubility method

Prior work had shown that the principal products of the pyrolysis of p-terphenyl are biphenyl and certain higher polyphenyls. Since the three terphenyls as well as particular higher polyphenyls are being investigated as heat transfer media for atomic energy reactors, the determination of biphenyl, as a major or minor product of their pyrolysis, becomes of prime importance in order to follow the trend of reaction products.Because of the greater solubility of biphenyl in water, as compared to other polyphenyls, biphenyl is completely extracted from such mixtures by water and can be determined spectrophotometrically in aqueous solution. Effects of temperature, rates of solution, and the presence of polyphenyls were studied. The solubility of biphenyl is about 0.9 mg/100 ml of water, but the suggested working limit in 0.4 mg biphenyl/100 ml of solvent.As little as 0.1% biphenyl in p-terphenyl may be detected and as high as 20% may be determined in higher polyphenyls.     

Quantitative Analysis of Caffeoylquinic Acids and Styrylpyrones in Sweetia panamensis Bark by UPLC

Six secondary metabolites from the methanolic extract of Sweetia panamensis (Fabaceae) bark were isolated and characterised. Along with the pyrones desmethylangonine β-d-O-glucopyranoside and desmethylangonine β-d-O-glucopyranosyl-(1→6)-O-β-d-glucopyranoside, already reported in this species, 5-O-caffeoylquinic acid (chlorogenic acid), 4-O-caffeoylquinic acid, 3-O-caffeoylquinic acid and the isoflavonoid 5-O-methylgenistein 7-O-β-d-glucopyranoside were isolated for the first time from S. panamensis. Additionally, an LC-ESI-MS qualitative analysis was performed and an ultra performance liquid chromatography (UPLC) method was developed and validated for the determination of these compounds. The UPLC method was applied to the quantitative analysis of plant samples. Pyrones and caffeoylquinic acids resulted to be the main compounds in the extract; in particular desmethylangonine β-d-O-glucopyranosyl-(1→6)-O-β-d-glucopyranoside was the most abundant compound.     

Kinetic optimisation of the reversed phase liquid chromatographic separation of rooibos tea (Aspalathus linearis) phenolics on conventional high performance liquid chromatographic instrumentation

Rooibos tea, produced from the endemic South African shrub Aspalathus linearis, has various health-promoting benefits which are attributed to its phenolic composition. Generating reliable, quantitative data on these phenolic constituents is the first step towards documenting the protective effects associated with rooibos tea consumption. Reversed phase liquid chromatographic (RP-LC) methods currently employed in the quantitative analysis of rooibos are, however, hampered by limited resolution and/or excessive analysis times. In order to overcome these limitations, a systematic approach towards optimising the RP-LC separation of the 15 principal rooibos tea phenolics on a 1.8 μm phase using conventional HPLC instrumentation was adopted. Kinetic plots were used to obtain the optimal configuration for the separation of the target analytes within reasonable analysis times. Simultaneous optimisation of temperature and gradient conditions provided complete separation of these rooibos phenolics on a 1.8 μm C18 phase within 37 min. The optimised HPLC–DAD method was validated and successfully applied in the quantitative analysis of aqueous infusions of unfermented and fermented rooibos. Major phenolic constituents of fermented rooibos were found to be a phenylpropanoid phenylpyruvic acid glucoside (PPAG), the dihydrochalcone C-glycoside aspalathin, the flavones isoorientin and orientin, and a flavonol O-diglycoside tentatively identified as quercetin-3-O-robinobioside. Content values for PPAG, ferulic acid and quercetin-3-O-robinobioside in rooibos are reported here for the first time. Mass spectrometric (MS) and tandem MS detection were used to tentatively identify 13 additional phenolic compounds in rooibos infusions, including a new luteolin-6-C-pentoside-8-C-hexoside and a novel C-8-hexosyl derivative of aspalathin reported here for the first time.     

Experimental matrix isolation and theoretical ab initio HF/6-31G(d,p) studies of infrared spectra of purine,adenine and 2-chloroadenine

The results of ab initio calculations at the Hartree—Fock level with the 6-31G(d, p) basis set are reported for the harmonic vibrational infrared spectra of purine, adenine and 2-chloroadenine. These were compared with the experimental IR spectra of the compounds isolated in low-temperature matrices. The experimental spectra of 2-chloroadenine are reported for the first time. In the case of purine this comparison resulted in the complete assignment of the experimental IR spectrum. The proposed assignments of both the adenines studied are still incomplete.     

A new strategy to iteratively update scalable universal quantitative models for the testing of azithromycin by near infrared spectroscopy

The training set of a universal near infrared (NIR) model for quantitative analysis of a drug should cover as many samples of this drug in the market as possible. Inevitably the model may fail for new products that have different excipients and production processes. In such circumstances the model should be updated. We here propose a new strategy to iteratively update a universal NIR quantitative model for azithromycin. We prove that universal quantitative models generated from this new strategy are comparably effective for azithromycin injection powders and azithromycin tablets, compared to the strategy using hierarchical clustering method which we reported previously. Furthermore, we establish the correlation coefficient r between a new sample and the training set samples can be used to decide whether or not the model should be updated.     

Benzocoumarins from the rhizomes of Juncus acutus

Investigation of the ethyl acetate extract of Juncus acutus rhizomes revealed seven benzocoumarins, probably derived from oxidation of phenanthrenes already isolated from the plant. The structures were determined by means of spectroscopic methods. The anti-algal activity of the isolated compounds tested on the green alga Pseudokirchneriella subcapitata are reported here.     

Qualitative and Quantitative Analysis of 17 Different Types of Tetra- and Pentacyclic Triterpenic Acids in Boswellia papyrifera by a Semi-Automatic Homomodal 2D HPLC method

A semi-automatic two dimensional high-performance liquid chromatography (HPLC) gradient method with photo diode array detection was developed, capable of separating and quantifying up to 17 different triterpenic acids in the gum resin of the frankincense species Boswellia papyrifera. The here reported quantitation of 14 of the possible 17 compounds contains boswellic, tirucallic and lupeolic acids. All compounds were isolated from B. papyrifera and used as external standards. Quantitation of these compounds was performed after minimizing the matrix by liquid?Cliquid separation, using alkaline, acidic and organic media to separate the acids from interfering matrix compounds. Therefore, two different extraction procedures were tested, giving two different extraction profiles. Within the first run (1st dimension) 13 compounds could be quantified. Quantitation of ??-boswellic acid, which was proved to elute as inhomogeneous peak, was achieved by introduction of a second dimension, leading to a fully validated semi-automatic homomodal 2D chromatography. The method is applicable for determination of compounds occurring in different types of frankincense and their pharmaceutical products. It also can be applied to distinguish between different kinds of frankincense. Moreover, it is the first published method feasible of separating and quantifying five different types of tirucallic acids.     

Evaluation of in vitro,in silico antidiabetic and antioxidant potential of bioactivity based isolated “Pakistanine” from Berberis baluchistanica

Bioassay based fractionation of methanolic extract of Berberis baluchistanica (Berberidaceae), used traditionally for internal injuries, led to the isolation of known compounds (1–4). The structure of these compounds was elucidated by different spectroscopic analysis and available literature data. Antidiabetic and antioxidant potentials of B. baluchistanica fractions and isolated compounds were evaluated using in vitro alpha- amylase and DPPH assays. The isolated compounds were identified as obamegine (1), pakistanine (2), 8-oxyberberine (3) and baluchistine (4). Obamegine was reported from many other species of this genus but it is first time isolated from B. baluchistanica in present study. Moreover, in vitro pakistanine (2) was found as bioactive lead molecule for hypoglycemic (IC₅₀:40.26 µg/ml) and antioxidant (IC₅₀:14.15 µg/ml) activities compared to acarbose (IC₅₀:33.68 µg/ml) and ascorbic acid (IC₅₀:0.41 µg/ml). To the best of our knowledge, no previous data were available for these biological activities. Additionally, in silico antidiabetic and antioxidant activity of pakistanine against two proteins, α-amylase (-9.7 kcal/mol) and tyrosinase (-8.7 kcal/mol) are reported here for the first time. The molecular docking binding interactions authenticate and support the above-mentioned activities and are helpful in predicting the mechanism of action of pakistanine (2).     

Compressed matrix thin film (CMTF)-assisted laser desorption ionization mass spectrometric analysis

The inhomogeneous re-crystallization process of matrix materials is the major concerns associated with matrix assisted laser desorption/ionization (MALDI) analysis. We describe here the approach termed compressed matrix thin film (CMTF) in order to make a uniform matrix deposition. In this approach, solid matrix particles are compressed under 10 MPa of pressure by a compressor that is regularly used in infrared spectroscopic analysis. Then aqueous samples can be deposited on the surface of the matrix film. Major advantages of the CMTF approach are summarized as follows. (1) Reproducible sample preparation procedure. Size and thickness of matrix thin films can be controlled by using a fixed mold.force and known amount of matrix materials. (2) Significantly decreased shot-to-shot variations and enhanced reproducibility. (3) Tolerance for in situ salt washing. Because matrix materials are hydrophobic, salts can be washed away while proteins or peptides are retained on the surface of matrix thin films through hydrophobic interactions. (4) Improved sensitivity. The hydrophobic coating of MALDI sample plate by matrix thin films prevents the spreading of samples across the plate and confines analytes to a small area, leading to increased local concentration. (5) A new means for tissue analysis. Tissue sections can be directly transferred to the uniform surface of matrix materials for reproducible and quantitative comparison of different molecules in different localization. The proposed CMTF should be an enabling technique for mass spectrometric analysis with improved correlations between signal intensities and sample quantities.     

Optimization and Validation of a Headspace Solid-Phase Microextraction with Comprehensive Two-Dimensional Gas Chromatography Time-of-Flight Mass Spectrometric Detection for Quantification of Trace Aroma Compounds in Chinese Liquor (Baijiu)

The detection of trace aroma compounds in samples with complex matrices such as Chinese liquor (Baijiu) requires a combination of several methods, which makes the analysis process very complicated. Therefore, a headspace solid-phase microextraction (HS-SPME) method coupled with two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS) was developed for the quantitation of a large number of trace compounds in Baijiu. Optimization of extraction conditions via a series of experiments revealed that dilution of the alcohol content of 8 mL of Baijiu to 5%, followed by the addition of 3.0 g of NaCl and subsequent SPME extraction with DVB/CAR/PDMS fiber coating over 45 min at 45 °C was the most suitable. To check the matrix effects, various model Baijiu matrices were investigated in detail. The quantitative method was established through an optimized model synthetic solution, which can identify 119 aroma compounds (esters, alcohols, fatty acids, aldehydes and ketones, furans, pyrazines, sulfur compounds, phenols, terpenes, and lactones) in the Baijiu sample. The developed procedure provided high recovery (86.79–117.94%), good repeatability (relative standard deviation < 9.93%), high linearity (R² > 0.99), and lower detection limits than reported methods. The method was successfully applied to study the composition of volatile compounds in different types of Baijiu. This research indicated that the optimized HS-SPME–GC×GC-TOFMS method was a valid and accurate procedure for the simultaneous determination of different types of trace compounds in Baijiu. This developed method will allow an improved analysis of other samples with complex matrices.     

Determination of residual anabolic steroid in meat by gas chromatography-ion trap-mass spectrometer

The use of natural and synthetic anabolic steroids in animal fattening has been prohibited in Taiwan and many countries because of their potential toxic effect on public health. This paper describes a newly developed gas chromatography-ion trap-mass spectrometry (GC-IT-MS) method for the quantitative determination of various residual anabolic steroids in meat. Anabolic steroid was derivatized with N-methyl-N-trimethylsilytrifluoroacetamide prior to GC-IT-MS analysis. MS² was employed for quantitative measurement. In addition, 2d-estradiol was used as an internal standard. Quantitative determination was based on the ratio of peak area of steroid derivative to peak area of internal standard derivative. Good linearity of each compound, 0.03-1.0 μg/ml, was determined. Solvent extraction was used to extract residual anabolic compounds in meat samples and a solid phase extraction (SPE) procedure was utilized for sample cleanup and pre-concentration. The limits of detection of anabolic compounds approximately ranged from 0.1 to 0.4 μg/kg. The detection limit was comparable with or better than reported methods and was below the minimum required performance limits (MRPLs) established by the European Community (EC). The application of this newly developed method was demonstrated by analyzing various beef, pork, chicken and several animal internal organ samples from local markets.     

Analytical performance of ETAAS method for Cd, Co, Cr and Pb determination in blood fractions samples

An electrothermal atomic absorption method (ETAAS) for direct determination of several toxic trace elements (Cd, Co, Cr, Pb) in human blood fractions was developed, because of increasing interest of toxic elements distribution in various blood constituents. Zeeman background correction and pyrolitically coated graphite tubes with L’vov platforms were used. Centrifugation was employed for the separation of blood fractions at different centrifugal conditions at 1200 × g and 3000 × g. The samples were acid-digested by HNO₃ in closed tubes under high temperature and pressure before injection into graphite furnace. Two common modifiers were used and were compared for their effectiveness to the determination of each analyte at the examined blood fractions. The effect of modifier, matrix, calibration technique and peak characteristic (peak area and peak height) on the total variation of the method was examined by analysis of variance. The sensitivity and recovery (Cd 98-110%, Cr 93-109%, Co 95-106% and Pb 91-107%) of the developed method are presented for the various fractions. The overall precision (R.S.D.) using peak area (Cd 6.3-13.1%, Cr 8.2-13.9%, Co 7.4-8.5% and Pb 7.0-11.8%) and peak height measurements (Cd 1.1-9.3%, Cr 6.5-13.5%, Co 6.5-17.3% and Pb 6.9-14.8%) are also presented for pellet and supernatant solution. Standard addition technique was more accurate in terms of analyte recovery.     

Isolation of Anti-Diabetic Active Compounds from Benincasae Exocarpium and Development of Simultaneous Analysis by HPLC-PDA

Diabetes is a chronic metabolic disease that is a constant problem. Previous studies have reported that Benincasa cerifera Savi. extracts are effective in treating diabetes and its complications. Benincasae Exocarpium (BE) is a fruit peel of B. cerifera that has been reported to be used for the prevention and treatment of metabolic diseases such as hyperglycemia, obesity, and hyperlipidemia. However, there are not enough studies on the compounds and bioassays to support the efficacy of BE. The inhibitory activity of the BE extracts and fractions against advanced glycation end-products (AGE) formation and α-glucosidase activity was evaluated. These assays are relevant for the treatment of type 2 diabetes and its complications. Based on these results, compounds 1–11 were isolated through bioassay-guided isolation. In addition, we developed a high-performance liquid chromatography (HPLC) method that can simultaneously analyze these 11 compounds. Activity evaluation of the compounds was also conducted, and eight compounds exhibited significant activity. Among these, flavonoid compounds showed strong activity. A quantitative evaluation of eight bioactive compounds (2, 5–11) was conducted. In conclusion, this study demonstrated the potential of BE for prevention and treatment of type 2 diabetes and its complications.     

Vibrational and electronic spectral studies of substituted 1,3-dihydro-1,3-diphenyl-2-thioxo-2H,5H-pyrimidine-4,6-diones

The vibrational spectra of 1,3-diphenyl-; 1,3-di (4′-chlorophenyl)-; 1,3-di(3′-methoxyphenyl)-1,3-dihydro-2-thioxo-2H,5H-pyrimidine-4,6-diones in solid state (KBr pellet) and in solution (CHCl₃ and CCl₄) have been studied and assignments made. Tautomeric and hydrogen bonding behaviour are discussed. Electronic spectra in various solvents at different pH values are recorded. The effect of substituents, change of solvent on the π—π* and n—π* transitions of all the compounds is explained. The bathochromic and hypsochromic shifts observed when the neutral form changes to the cationic or anionic form depending on the pH of solution, are also discussed.     

Study of the Phase Transitions of (DI-DCNQI)2M (M=Ag, Li,Cu) through the Analysis of the Temperature-Dependent Vibronic and Vibrational Infrared Absorptions

The temperature-dependent phase transitions of 2,5 diiodo-dicyanoquinondiimmine (2,5-DI-DCNQI) title compounds are analyzed by looking at the bond order wave (BOW) and at the charge density wave (CDW) which characterizes the transitions. The analysis is done by studying the temperature-dependent powder infrared spectra which allow one to have a separate evaluation of both types of contribution to the phase transition of these molecular metals. A model for the spectroscopic infrared features related to the transitions is reported and used for the analysis. It is found that all the title compounds develop a BOW structure at low temperatures with characteristics which recall an instability toward a tetramerized 2k_F periodicity particularly for the Ag and Li compounds. An appreciable CDW amplitude contribution to the transitions is not found in the spectra.     

Palladium and the electrochemical quartz crystal microbalance: a new method for the in situ analysis of the precious metal in aqueous solutions

A new method for the quantitative determination of palladium(II) by the electrochemical quartz crystal microbalance (EQCM) technique has been developed. Using a bare carbon-coated quartz crystal, Pd(II) ions are directly deposited from aqueous solution as palladium metal onto the crystal surface, and the Pd(II) concentration is determined with a detection limit of 0.0156 mM, or 1.66 ppm. No complexing agent or preconcentration of palladium is required for the analysis. The palladium is stripped from the crystal through its electrochemical oxidation, regenerating the crystal for subsequent multi-cycle palladium analyses. A conventional gold-coated quartz crystal was incapable of carrying out the same measurements. The EQCM technique presented is simple, sensitive, and reproducible for the detection of this widely used precious metal.     

Theoretical and matrix-isolation experimental study of the infrared spectra of 5-azauracil and 6-azauracil

The infrared absorption spectra of 5-azauracil and 6-azauracil isolated in low-temperature Ar and N₂ matrices are reported. Within the limits of accuracy of spectroscopic measurements, both compounds appear to exist, in Ar and N₂ matrices, exclusively in dioxo tautomeric forms. An assignment of the observed infrared absorption bands is proposed based on the comparison of experimental frequencies and intensities with those calculated theoretically at ab initio Hartree-Fock level with 6-31G** basis set. Infrared spectra predicted at this level of theory reproduce the experimental spectra sufficiently accurately to enable a reliable assignment. Basis set dependency (6-31G**, 3–21G) of the theoretical result was also accounted for and it turned out that for accurate prediction of frequencies and intensities the use of basis set augmented with polarization functions is of crucial importance.     

Application of attenuated total reflectance Fourier transform infrared spectrometry to the determination of sodium percarbonate in washing powder detergent

In this paper, a novel and precise analytical procedure has been developed for quantitative determination of sodium percarbonate (SPC) in washing powder. The method is based on the partial least squares (PLS) treatment of data obtained by attenuated total reflectance Fourier transform infrared (ATR FT-IR) spectrometry in wavenumber region of 1435-1342 cm⁻¹. The statistical parameters such as R², RSD, SEC and SECV have been evaluated, and number of factors, number of scan and the resolution have been optimized. In this method R² and RSD for five independent analyses of a 0.552 g per 100 g solution of SPC, SEC for 10 standard samples and SECV for five validation samples were 0.998, 1.011, 0.002 and 0.039 respectively.Results obtained for six different commercial washing powders compared well with those obtained with a standard method.