Optimization and comparison of two digestion methods for multi-element analysis of certified reference plant materials by ICP-AES. Application of Plackett-Burman and central composite designs

Two open-vessel wet digestion methods using mixtures of (i) HNO₃ and H₂SO₄ (WD I), and (ii) HNO₃, H₂SO₄ and H₂O₂ (WD II) were developed and optimized for determination of a wide range of elements in plant reference materials by inductively coupled plasma atomic emission spectrometry. A Plackett-Burman fractional factorial experimental design with eight experiments for seven variables was used for the evaluation of the effects of several digestion variables at once. From these studies, certain variables showed up as significant, and they were further optimized by using a star-type central composite experimental design, which involved fourteen experiments. Instrumental variables such as radio-frequency incident power, nebulizer argon gas flow rate and sample uptake flow rate were also optimized. The analytical performance was assessed statistically. Nine elements in total can be simultaneously determined at the concentration levels usually found in plant materials. The agreement between measured and certified values with respect to NIST-SRM 1568a (rice flour), IAEA-331 (spinach leaves) and IAEA-359 (cabbage) proved that the developed methods are well suited for routine elemental analysis of plants or foods of plant origin. Correspondence: George A. Zachariadis, Laboratory of Analytical Chemistry, Department of Chemistry, Aristotle University, GR-54124 Thessaloniki, Greece     

Determination of Saikosaponins in Bupleuri Radix by Micellar Electrokinetic Chromatography with Experimental Design

The important pharmacological components of Bupleuri radix include saikosaponins a–d. A multivariable approach with experimental design was employed in this study to determine four saikosaponins in different species of Bupleuri radix by cyclodextrin-modified micellar electrokinetic chromatography. Compared to traditional multiple-parameter investigations, the current experimental design can shorten the time necessary for method development, and the multivariable approach can be used to evaluate the separation capability of the method and to explore the interactions of the different parameters. The significant influences of two experimental variables, including the concentration of γ-cyclodextrin and the percentage of methanol, on the responses were investigated using chromatographic resolution statistics. The optimized conditions were as follows: 25?mM of borate (pH 9.18) containing 50?mM of sodium dodecyl sulfate, 5?mM of γ-cyclodextrin, and 15% methanol (v/v) as running buffer. After the separation conditions were optimized and good resolution was acquired, solid phase extraction was performed to reduce the interference of crude extracts of Bupleurum kaoi and Bupleurum chinense DC. The simple and rapid analytical method was successfully applied, allowing for the determination of four saikosaponins and the identification of species of Bupleuri radix.     

Optimization of a high-performance liquid chromatography system by artificial neural networks for separation and determination of antioxidants

A high-performance liquid chromatography (HPLC) system was used to determine the antioxidants tert-butyl-hydroquinone (TBHQ), tert-butylhydroxyanisole (BHA), and 3,5-di-tert-butylhydroxytoluene (BHT) simultaneously in oils. The paper presents a new methodology for the optimized separation of antioxidants in oils based on the coupling of experimental design and artificial neural networks. The orthogonal design and the artificial neural networks with extended delta-bar-delta (EDBD) learning algorithm were employed to design the experiments and optimize the variables. The response function (Rf) used was a weighted linear combination of two variables related to separation efficiency and retention time, according to which the optimized conditions were obtained. The above-mentioned antioxidants in rapeseed oils were separated and determined simultaneously under optimized conditions by HPLC with UV detection at 280 nm. Linearity was obtained over the range of 10-200 microg/mL with recoveries of 98.3% (TBHQ), 98.1% (BHT), and 96.2% (BHA).     

The glucocorticoid derivative with the phthalimide group cationic nanocrystal for ophthalmic application: a design space development approach

The glucocorticoid derivative of budesonide with a phthalimide group is a drug candidate to treat inflammatory eye diseases; nevertheless, it presents low water solubility. Drug nanocrystals have been proposed to overcome this hurdle. The development of an innovative ophthalmic anti-inflammatory nanosuspension was performed using a design space approach. We obtained the particle size reduction of this glucocorticoid derivative on a nanometer scale (approximately 165.0 nm), applying wet bead milling on a super reduced scale. The design of experiment supported the optimization of the formula evaluating the parameters that influence reducing the particle size and also allowed determining the design space. Considering the two statistical models developed and the size range obtained, we proposed that the optimized formulation for the glucocorticoid derivative nanosuspension may be 1.0 wt% glucocorticoid derivative and 0.092 wt% cetylpyridinium chloride. This formulation was characterized by the morphological, physical–chemical, and mucoadhesive in vitro test and showed potential for ophthalmic use with reduced frequency of product application, improved efficiency, and safety, which may promote better patient compliance.     

季铵盐高分子抗菌剂的工艺优化与抗菌性能研究

采用正交实验设计,进行公斤级批量制备DMAEMA-DB季铵盐单体和抗菌聚合物的研究,对影响单体合成的关键因素以及聚合的条件进行优化,并采用FT-IR和NMR等方法对所合成的单体和聚合物分别进行了结构表征,通过平板活菌计数法测定了单体以及聚合物的抗菌性能.结果表明,DMAEMA-DB单体的优化合成条件为:反应温度55℃,反应时间30h,反应物浓度为V<,s>:V<,l>=1:1,反应物配比为DMAEMA:DB=1:1.1.Poly(AAm/DMAEMA-DB)的最佳合成工艺条件为:聚合温度70℃,聚合时间8h,单体浓度为0.4mol/L,引发剂用量为单体用量的0.4mol%,在该条件下合成的聚合物平均得率达89%.将它们用于杀灭大肠杆菌时,接触时间5min对大肠杆菌的抑菌率可达99%,接触时间30min抑菌率达到100%.     

Ab Initio Calculations on Nitramide and Its Methyl Derivatives( Ⅱ )——The Harmonic Force Fields and Vibrational Spectra of Nitramide and Its Isotopic Derivatives

The harmonic force field and the vibrational spectrum of nitramide were calculated by using the ab initio gradient program TEXAS at the Hartree-Fock level with a 4-21G basis set. The directly computed theoretical harmonic force field was scaled by using empirical scale factors which are transferred from other molecules and provided an a priori prediction of fundamental frequencies and intensities. The average deviations between predicted vibrational frequencies of nitramide and experimental IR spectrum in an argon matrix are 63 cm-1 for symmetric vibrations and 41 cm-1 for antisymmetric modes. A new set of scale factors was optimized in this paper. These scale factors reduced the average deviations to 2. 3 cm-1 for symmetric modes and 0. 8 cm-1 for antisymmetric ones. The vibrational spectra of three isotopic derivatives of nitramide were predicted by using the force field resulted from the optimized set of scale factors, which are in good agreement with their experimental data in an argon matrix.     

Leaching behavior of uranium and vanadium using strong sulfuric acid from Korean black shale ore

The present scientific study focused on leaching behavior of uranium and vanadium from Korean domestic ore. The leaching process experimental conditions optimized for uranium and vanadium metals recovery from Korean domestic ore and developed the basic experimental procedures such as time, particle size, acid influence, temperature effect and pulp density (PD) behavior. Acid influence on leaching process was tested and noted that 2.0 M sulfuric acid concentration is the optimized conditions for present study. The time influence on leaching process was observed and its optimized 2 h for complete leaching process. The temperature influence tested and optimized the 80 °C for complete leaching process and PD is 50 % (wt%). The bench scale experiments developed in a laboratory and tested in pilot level each batch 100 kg of ore sample.     

在中性条件下用亚氯酸钠和双氧水氧化芳香醛

本文优化了中性环境中亚氯酸钠和双氧水氧化醛的反应条件,采用正交实验设计法考察了溶剂、亚氯酸钠和双氧水的用量以及反应温度对醛氧化产率的影响,确定最佳工艺条件为以乙醇作溶剂,亚氯酸钠、双氧水、醛的摩尔比为1.1: 2: 1。在优化的反应条件下对醛进行底物扩展验证其适应性,并通过放大实验说明其工业生产适用性,本方法具有产率高、后处理简单、副产物绿色无污染的优点。     

Quality‐by‐design‐based ultra high performance liquid chromatography related substances method development by establishing the proficient design space for sumatriptan and naproxen combination

Quality‐by‐design‐based methods hold greater level of confidence for variations and greater success in method transfer. A quality‐by‐design‐based ultra high performance liquid chromatography method was developed for the simultaneous assay of sumatriptan and naproxen along with their related substances. The first screening was performed by fractional factorial design comprising 44 experiments for reversed‐phase stationary phases, pH, and organic modifiers. The results of screening design experiments suggested phenyl hexyl column and acetonitrile were the best combination. The method was further optimized for flow rate, temperature, and gradient time by experimental design of 20 experiments and the knowledge space was generated for effect of variable on response (number of peaks ≥ 1.50 – resolution). Proficient design space was generated from knowledge space by applying Monte Carlo simulation to successfully integrate quantitative robustness metrics during optimization stage itself. The final method provided the robust performance which was verified and validated. Final conditions comprised Waters® Acquity phenyl hexyl column with gradient elution using ammonium acetate (pH 4.12, 0.02 M) buffer and acetonitrile at 0.355 mL/min flow rate and 30°C. The developed method separates all 13 analytes within a 15 min run time with fewer experiments compared to the traditional quality‐by‐testing approach.     

Simultaneous determination and validation of emtricitabine,rilpivirine and tenofovir from biological samples using LC and CE methods

A combination of antiretroviral agents is frequently used in effective treatment of the human immunodeficiency virus infection. In this study, two different separation methods are presented for the simultaneous determination of emtricitabine, rilpivirine and tenofovir from raw materials and urine samples. Developed liquid chromatography and capillary electrophoresis methods were thoroughly optimized for high analytical performances. Optimization of multiple variables at the same time by performing a minimum number of experiments was achieved by the Box–Behnken design, which is an experimental design in response surface methodology, in capillary electrophoresis. The results of the experimental design ensure minimum analysis time with well‐separated analytes. Separation conditions, such as different stationary phases, pH level, organic modifiers and temperatures in liquid chromatography method, were also optimized. In particular, among stationary phases, the core–shell column especially enhanced the effectiveness of separation in liquid chromatography. Both methods were fully validated and applied to real samples. The main advantage of the developed methods is the separation of the drug combination in a short time with high efficiency and without any time‐consuming steps.     

Experimental design approach for petrochemical waste water treatment using solar assisted photo Fenton process

In this study, the effect of photo-Fenton process on the treatment of petrochemical waste water treatment was investigated. The influence of process conditions were determined by factorial design. Optimization of the process conditions were performed by central composite design. Under, optimized conditions lab scale and solar assisted pilot scale of petrochemical waste water treatment was performed. Three factors namely initial pH, H₂O₂ concentration (mM) and Fe²⁺ concentration (mM) executed the essential role in petrochemical waste water treatment. Central composite design resulted in the prediction of optimized value as 6.5 initial pH, 15.65 mM of H₂O₂ concentration and 2.09 mM of Fe²⁺ concentration. Under these conditions, the reduction in chemical oxygen demand (COD) percentage reached about 68.67 ± 2.8% after 280 min in pilot scale of solar assisted photo Fenton process of petrochemical waste water treatment. Thus, experimental design combined with advanced Fenton process can become a feasible unconventional method for petrochemical waste water treatment.     

Chromatographic Behavior of Fosinopril Sodium and Fosinoprilat Using Neural Networks

In this paper, the chromatographic characterization of fosinopril sodium and fosinoprilat is presented. The first stept was pK _a determination for the active substance and its degradation product using RP-LC. It was followed by optimization employing the combination of experimental design and artificial neural networks. For the definition of input and output variables, the central composite design for three factors was built. Back propagation algorithm was applied to model the system, and then the optimization of the experimental conditions was carried out in the neural network with 3-8-2 structure, which confirmed to be able to provide the maximum performance. From the method optimization, the most appropriate experimental conditions for fosinopril sodium and fosinoprilat analysis were extracted. The optimized method was validated and applied in the quality control of tablets and for forced degradation studies.     

硝胺及其甲基衍生物的从头计算研究 3: 甲硝胺及其同位素衍生物的谐性力场和振动光谱

用TEXAS从头计算程序,取STO-4-21G基组,计算了甲硝胺的谐性力场和振动光谱.直接理论计算的谐性力场经由其他分子转移来的经验校正因子校正后,提供了甲硝胺振动基频的预测.预测值和甲硝胺分子在气相中的振动光谱实验值之间的平均偏差为31cm^-1.为了获得更合适的气相甲硝胺振动力场和预测它的同位素衍生物的振动光谱,我们优化了一组新的校正因子,使理论值和实验值的平均偏差减为8.9cm^-1.用这组校正因子得到的力场预测了三个同位素衍生物的振动光谱,其同位素位移的理论预测值和实验值符合良好.     

An application of factorial design to the development of fused silica capillary columns

Stationary phase crosslinking conditions for fused silica capillary columns were optimized with the use of a factorial design experiment. This experimental strategy was chosen because it provided for the determination of two-factor interactions. A predictive model was developed for the desired chromatographic performance parameters as a function of the variables of the crosslinking reaction. Confirmatory experiments proved the usefulness of the mathematical model which resulted in the production of capillary columns of superior performance with significant improvements in reproducibility.     

Experimental study on the optimization of general conditions for a free‐flow electrophoresis device with a thermoelectric cooler†

With a given free‐flow electrophoresis device, reasonable conditions (electric field strength, carrier buffer conductivity, and flow rate) are crucial for an optimized separation. However, there has been no experimental study on how to choose reasonable general conditions for a free‐flow electrophoresis device with a thermoelectric cooler in view of Joule heat generation. Herein, comparative experiments were carried out to propose the selection procedure of general conditions in this study. The experimental results demonstrated that appropriate conditions were (i) <67 V/cm electric field strength; (ii) lower than 1.3 mS/cm carrier buffer conductivity (Tris‐HCl: 20 mM Tris was titrated by HCl to pH 8.0); and (iii) higher than 3.6 mL/min carrier buffer flow rate. Furthermore, under inappropriate conditions (e.g. 400 V voltage and 40 mM Tris‐HCl carrier buffer), the free‐flow electrophoresis separation would be destroyed by bubbles caused by more Joule heating. Additionally, a series of applications under the appropriate conditions were performed with samples of model dyes, proteins (bovine serum albumin, myoglobin, and cytochrome c), and cells (Escherichia coli, Streptococcus thermophilus, and Saccharomyces cerevisiae). The separation results showed that under the appropriate conditions, separation efficiency was obviously better than that in the previous experiments with randomly or empirically selected conditions.     

The computed force constants and vibrational spectra of toluene

The complete harmonic force field and dipole moment derivatives have been computed for toluene at the Hartree-Fock level using a 4-21G basis set. The six scale factors optimized for benzene were used to scale the computed harmonic force constants of toluene. The vibrational frequencies of toluene computed from this scaled quantum mechanical force field are quite good. After a correction was made to two previously proposed spectral assignments, the mean deviation from the experimental frequencies is only 7.8 cm^?1 except for the frequencies related to the methyl group. Five more scale factors for the vibrational modes of the methyl group were reoptimized. The final comparison showed an overall mean deviation of 7.5 cm^?1 between the theoretical spectrum and the experimental spectrum. Computed intensities are qualitatively in agreement with experiments. They are highly useful in the investigation of questionable assignments.     

Multivariate optimization in the biosynthesis of a triethanolamine (TEA)-based esterquat cationic surfactant using an artificial neural network

An Artificial Neural Network (ANN) based on the Quick Propagation (QP) algorithm was used in conjunction with an experimental design to optimize the lipase-catalyzed reaction conditions for the preparation of a triethanolamine (TEA)-based esterquat cationic surfactant. Using the best performing ANN, the optimum conditions predicted were an enzyme amount of 4.77 w/w%, reaction time of 24 h, reaction temperature of 61.9 °C, substrate (oleic acid: triethanolamine) molar ratio of 1:1 mole and agitation speed of 480 r.p.m. The relative deviation percentage under these conditions was less than 4%. The optimized method was successfully applied to the synthesis of the TEA-based esterquat cationic surfactant at a 2,000 mL scale. This method represents a more flexible and convenient means for optimizing enzymatic reaction using ANN than has been previously reported by conventional methods.     

Response surface methodology based on central composite design accompanied by multivariate curve resolution to model gradient hydrophilic interaction liquid chromatography: Prediction of separation for five major opium alkaloids

Hydrophilic interaction liquid chromatography on bare silica presents some benefits for analysis and purification of ionizable basic alkaloids. This mode was used to separate five major opium alkaloids: morphine, codeine, thebaine, papaverine, and noscapine. Central composite design based on response surface methodology was applied for experimental design, modeling, and optimization in a single‐step gradient method. The main effects and their interactions (initial percentage of modifier, changing range of modifier in run time, pH of buffer, and its concentration) were investigated in 30 experiments. Multivariate curve resolution‐alternating least squares, by resolving overlapped curves, helped in the accurate calculation of baseline resolution factors to be modeled and optimized more accurately. Then three crucial resolution factors besides elution time were modeled in quadratic and cubic equations and optimized. In addition to the four factors, five extra logarithmic, and nonlogarithmic factors extracted from the four factors to give nine factors overall were inspected on mechanism of retention. It was shown that a linear combination consist of four independence variables successfully describes morphinans retentivity in a single‐step gradient method.     

Development of generic liquid chromatography-mass spectrometry methods using experimental design

Standard approaches to development of liquid chromatography-mass spectrometry (LC-MS) methods, either ion-pairing or reversed-phase liquid chromatography, have been through trial and error or intentional variation of experimental factors. These approaches to method optimization fail to take into account interactions between experimental factors and therefore the results may not be optimal for the combination of experimental factors. Another approach to optimization is through the use of chemometrics. Chemometric approaches can be more efficient than trial and error or intentional variation because chemometrics make use of multivariate designs; experimental factors are varied simultaneously at the various levels. Therefore chemometrics can take into account interactions between factors. The goal of this study was to develop a generic ion-pair LC-MS method for the analysis of acidic compounds using a chemometric approach called design of experiments (DOE). Four acidic compounds which cover three classes of acidic functional groups: 1-naphthyl phosphate (1), 1-naphthalenesulfonic acid (2), 2-naphthalenesulfonic acid (3), and (1-naphthoxy)acetic acid (4) were used as model compounds to develop the generic method. This study illustrates that LC-MS conditions can be optimized efficiently with minimal amount of experimentation using a chemometric approach to experimental design.     

Revisiting the design of experiments for copolymer reactivity ratio estimation

Tidwell and Mortimer used the D-optimal criterion to design terminal model reactivity ratio estimation experiments. In this paper, two problems are investigated which were not addressed by Tidwell and Mortimer. The first problem is the design of reactivity ratio estimation experiments subject to composition constraints. It is shown that all the key information contained in the D-optimal criterion can be summarized in two equations: one which is a function of r?₁, and one which in a function of r?₂. These two equations can be used to design reactivity ratio estimation experiments under composition constraints which are within 3 mol % of the D-optimal feed compositions. The second problem is the design of penultimate reactivity ratio estimation experiments. The D-optimal criterion for the penultimate model was derived and optimized for two existing systems as well as a large number of hypothetical systems. The D-optimal criterion for the penultimate model was found to be much more complicated than the terminal model criterion. For this reason, the optimal penultimate reactivity ratio estimation experiments can not be approximated by simple equations. Anyone interested in designing such experiments must derive and optimize the D-optimal criterion. © 1993 John Wiley & Sons, Inc.