Introduction Chemometrics observes each process as a system consisting of certain elements. By applying Design of Experiments (DoE) it is possible to change several factors simultaneously, performing a relatively small
samples and pharmaceutical preparations have been described in the literature, with the most recent method including HPLC, LC-MS, spectrophotometric, IR spectroscopic and fluorescence polarization immunoassay methods [ 5–11 ]. Design of Experiments (DoE
This paper describes a statistical-experimental design approach for identifying sources of Pu contamination in the radioactivity material analysis of dried shellfish at the National Institute of Standards and Technology (NIST). Identification and elimination of sources of contamination were required for certifications of the radioactivity concentration of actinides in the proposed reference material. Sources of contamination included the fume hood, glassware, and reagents. The experimental design employed reduced number of required experiments by a factor of 100. The result is an orthogonal design of experiment (ODEX) and subsequent data was analyzed using Exploratory Date Analysis (EDA), which narrowed the 200+ experiments to a manageable 16. This design made it possible to identify the sources and interactions of sources of contamination in a timely and cost effective manner.
The objective of this study was to establish and optimize high-performance thin-layer chromatography (HPTLC) analysis of gatifloxacin and related substances by the method of design of experiment (DOE). First, preliminary screening of 22 solvents was performed using uniform design (UD) to establish the developing solvent proposed to be optimized. The optimal proportions of components in the developing solvent were established by using central composite design (CCD) to establish and validate HPTLC analysis of gatifloxacin and related substances. Using DOE, it was found that the optimal proportions (by volume) of components in the developing solvent in the HPTLC analytical method were methanol-1,2-dichloroethane-concentrated ammonia solution-acetonitrile (2.8:7.2:0.5:0.5, v/v). Methodological validation showed that the established HPTLC method could separate gatifloxacin and 8 related substances with similar structures effectively. In particular, impurity pairs with the greatest separation difficulty (due to their similar polarities and dipole moments), e.g., impurity #3 (8-fluorogatifloxacin) and impurity #8 (gatifloxacin 2-methylpiperazine), impurity #3, and substance #9 (gatifloxacin), could also be separated effectively. The HPTLC method was simple, accurate, reliable, and suitable for rapid qualitative analysis of gatifloxacin and related substances in routine tests. Additionally, the analytical results presented here may provide useful supplemental information on the current reversed phase high-performance liquid chromatography (RP-HPLC) method, especially in terms of the mechanism of normal-phase separation.
In the present study, a design-of-experiment (DoE) approach Was used to determine optimized mobile-phase compositions for the development of a high-performance thin-layer chromatography (HPTLC) method for the simultaneous estimation of berberine chloride (BER-H) and galangin (GAL) in Tinospora cordifolia M. and Alpinia galanga L., respectively, and their formulations. A Box‒Behnken design (BBD) was used to optimize the compositional parameters and evaluate the main effect, interaction effects and quadratic effects of the mobile-phase compositions on the retardation factor (R F) of both drugs. HPTLC separation was performed on aluminum plates pre-coated with silica gel 60 F254 as the stationary phase, using toluene‒ethyl acetate‒formic acid (3:6:1, v/v) as the mobile phase at a wavelength of 267 nm. A sharp and well-resolved peak was obtained for BER-H and GAL at R F values of 0.17 ± 0.01 and 0.82 ± 0.01, respectively. The calibration curve was in the range of 200–1200 ng per band for both BER-H and GAL, with r 2 = 0.984 and r 2 = 0.980, respectively. Statistical insight was achieved with analysis of variance (ANOVA). The method was validated for linearity, accuracy, precision, limit of detection, limit of quantification, robustness, and specificity. To provide a better visualization of the statistically significant factors derived from the statistical analysis, the perturbation plot and response surface plot for the effect of independent variables on the R F of BER-H and GAL were evaluated. The developed HPTLC method was found to be simple, accurate, precise, sensitive, and specific for the simultaneous quantification of berberine chloride and galangin in Tinospora cordifolia M. and Alpinia galanga L., respectively, and their formulations.
In the present study, a design of experiment (DoE) approach was used to optimize chromatographic conditions for the development of a high-performance thin-layer chromatography (HPTLC) method for the simultaneous estimation of metformin hydrochloride (MET) and ursodeoxycholic acid (URSO) in pharmaceutical dosage form. The critical factors were identified using a Taguchi design, and after identification of critical factors, optimization was done using Box-Behnken design (BBD). BBD was used to optimize the compositional parameters and to evaluate the main effect, interaction effects, and quadratic effects of the mobile phase compositions, development distance, and saturation time on the retardation factor (R F) of both drugs. HPTLC separation was performed on aluminum plates pre-coated with silica gel 60 F254 as the stationary phase, using toluene–ethanol–acetone–formic acid (4.5:2:2.5:0.85, V/V) as the mobile phase at a wavelength of 234 nm and 700 nm for MET and URSO, respectively. A sharp and well-resolved peak was obtained for MET and URSO at R F values of 0.19 and 0.80 min, respectively. The calibration curve was in the range of 5000–40000 ng per spot and 1500–12000 ng per spot for MET and URSO, with r 2 = 0.984 and r 2 = 0.980, respectively. The method was validated for linearity, accuracy, precision, limit of detection, limit of quantification, and specificity. To provide a better visualization of the statistically significant factors derived from the statistical analysis, the perturbation plot and response surface plot for the effect of independent variables on the R F of MET and URSO were evaluated. Stability study was performed under different stress conditions such as acid and alkali hydrolysis, oxidation, and temperature. The developed method was able to resolve drugs and their degradation products formed under the afore-mentioned conditions.
A series of substituted indole-2-carboxylic acid ethyl esters and aza-indole analogs have been prepared using continuous-flow hydrogenation. The identification of some key parameters using a design of experiments (DoE)-based approach allowed efficient optimization of each synthesis. The scale-up study for the multigram preparation of one model indole substrate showed the importance of working at steady state with the H-Cube pparatus. A new useful method for the easy preparation of substituted indoles in various quantities is presented.
Non-reinforced and reinforced Poly-Ether-Ether-Ketone (PEEK) plastics have excellent mechanical and thermal properties. Machining is an efficient process that can be used to manufacture specific mechanical parts made from PEEK composites. Researchers have focused on improving the performance of machining operations with the aim of minimizing costs and improving quality of manufactured products, in order to get the best surface roughness and the minimum cutting force. The parameters evaluated are the cutting speed, the depth of cut and the feed rate. In this paper, the effect of the mentioned parameters on surface roughness and cutting force, in dry turning of reinforced PEEK with 30% of carbon fibers (PEEK CF30) using TiN coated cutting tools, is analyzed through using robust design techniques such as Taguchi's design method, signal-to-noise (S/N) ratio and statistical analysis tools such as Pareto-ANOVA. The obtained results have shown that Taguchi method and Pareto ANOVA are suitable for optimizing the cutting parameters with the minimum possible number of experiments, and the optimized process parameters were determined for surface roughness and cutting force criteria.
A simple, specific, and quantitative high-performance thin-layer chromatographic (HPTLC) method has been developed for the quantitative determination of lupeol in 2 marketed formulations, namely, Manasamitra vatakam and Amree plus capsule. Chromatographic development was performed by using a pre-coated silica gel 60 F254 aluminum-backed plate, and the development was carried out using toluene-ethyl acetate (9.48:0.52, V/V) as the optimized mobile phase. The developed TLC plates were derivatized by using anisaldehyde-sulfuric acid reagent. The detection of lupeol was carried out at 600 nm. Box-Behnken design was applied for optimization of the chromatographic conditions, and combinations of factors, such as mobile phase composition (volume of ethyl acetate) (A), chamber saturation time (B), and migration distance (C) likely to affect R F were identified from preliminary trials and further optimized using a response surface design. Among 3 factors, the significant factor found was the volume of ethyl acetate that resulted in higher change in the R F value and can be considered as a critical method parameter. Full factorial design was applied for optimization of extraction efficiency. The factors selected for the optimization process were volume of methanol (A) and duration of extraction (B) with percentage yield of extract as response. The linear ranges were found to be 500–3000 ng per band. The accuracy and precision measured were less than 2% relative standard deviation for lupeol. The sensitivity of the method in terms of the limit of detection (LOD) and the limit of quantification (LOQ) was measured. The proposed method was found to be accurate, precise, reproducible, robust, and specific and can be applicable for the determination of lupeol in the quality-control testing of extract and polyherbal formulations.
. Eriksson , L. ; Johansson , E. ; Kettaneh-Wold , N. ; Wikström , C. ; Wold , S. Design Of Experiments: Principles and Applications, 3rd edn. Umetrics AB, Umeå Learnways AB: Umeå, Stockholm, 2008