Derringer's Desirability Function Research Articles

Advantages of online supercritical fluid extraction and chromatography hyphenated to mass spectrometry to analyse plastic additives in laboratory gloves

Plastic additives are introduced in plastic material formulations, along with organic polymers, to offer different properties such as stability, plasticity or color. However, plastic additives may migrate from the plastic material to the content (in case of plastic containers) or to the material in contact with the plastic, like human skin. In the case of plastic medical devices, this migration is of particular interest, as plastic additives may be deleterious to health. In the present paper, we examined the interest of combining supercritical fluid extraction (SFE) to supercritical fluid chromatography (SFC) hyphenated to mass spectrometry (MS) in an online system to characterize plastic additives in laboratory gloves, taken as samples of medical devices. A set of target compounds comprising 18 plasticizers, 4 antioxidants and 2 lubricants was defined and their detectability with MS was examined, where it appeared that electrospray ionization (ESI) provided better detectability than atmospheric pressure chemical ionization (APCI). After examining possible stationary phases with the help of Derringer desirability function, an isocratic chromatographic method (CO2:methanol 95:5) was developed on Shim-pack UC Phenyl column. The extraction method was examined with a 3-level full factorial design of experiments to optimize the extraction temperature (40 °C) and pressure (200 bar). The online SFE-SFC-MS method was compared to offline methods where the samples were extracted with liquid solvents at atmospheric pressure or high pressure then analysed with SFC-MS. In all cases, offline methods showed significant contaminants (like the oleamide lubricant) issuing from laboratory plastic materials as nitrogen drying station, syringes and filters, while the online method allowed a complete elimination of laboratory contaminations. Furthermore, the online method saved time, solvents and laboratory consumables. It will also show that transferring a compressible fluid from a loading loop is favourable to high efficiency, as the resulting chromatographic peaks are much thinner than when transferring a liquid. Compared to injecting liquid heptane, the efficiency increase was 3.4-fold, while compared to injecting liquid methanol (a common practice in SFC), the efficiency increase was 13-fold. Finally, the additive composition of different laboratory gloves was compared.

Design of experiments and Derringer's desirability function in optimisation and validation of RP-HPLC method for the analysis of enrofloxacin and its impurities

AbstractUsing the Design of Experiments methodology (Response-Surface Methodology and Derringer's Desirability Function), a simple, fast and robust RP-HPLC method was developed for the analysis of enrofloxacin (EFC), its impurity A (fluoroquinolonic acid, FQ) and impurity B (ciprofloxacin, CPX). Gradient elution of samples was performed on a Zorbax Eclipse XDB C18 column (150 × 4.6 mm, 3.5 μm) with a mobile phase consisting of 32 mM phosphate buffer pH 3.5 – methanol (0 min-19.6% methanol; 15.5 min-19.6% methanol; 29.5 min-80% methanol; 30 min-19.6% methanol; 35 min-19.6% methanol), delivered at a flow rate of 1.5 mL min−1, wavelength of detection 278 nm (for EFX and CFX) and 265 nm for FQ. A good linear response was achieved in the range 15–35 μg mL−1 (EFX) and LOQ-150% for impurities (CFX and FQ). Other validation parameters were also tested: precision, accuracy, sensitivity and robustness. The developed method was shown to be simple, practical and suitable for the analysis of EFC and its impurities (CPX, FQ) in veterinary drugs.

Two-pot optimization of nutrient sources to enhance antioxidants in Citrus reticulata peel powder through solid-state fermentation with Aspergillus niger CGMCC 3.6189

This study aimed to optimize nutrient sources for enhancing the accumulation of antioxidants in Citrus reticulata peel powder (CRPP) through solid-state fermentation (SSF) using Aspergillus niger CGMCC 3.6189. A Plackett-Burman design revealed that four medium compositions, including yeast extract, NH4Cl, CaCl2, and MgCl2, significantly affected antioxidant accumulation in fermented CRPP. The optimal concentrations of these four compositions were predicted as 13.86, 0.40, 0.06, and 0.04 mg/g of CRPP, respectively, using a Box-Behnken design (BBD) when simultaneous optimization of total phenolic content (TPC), total flavonoid content (TFC), 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging capacities using Derringer's desirability function. Under the optimal medium compositions, TPC, TFC, ABTS, and DPPH scavenging capacities of fermented CRPP (FO-CRPP) increased by 25.2%, 26.9%, 45.8%, and 57.3%, respectively, in comparison with the unfermented CRPP (UF-CRPP). The HPLC analysis exhibited notable decreases in the levels of hesperidin, narirutin, nobiletin, and tangeretin, while enhancements in the contents of p-coumaric acid, ferulic acid, narirutin, and hesperetin in FO-CRPP compared to UF-CRPP were observed. Scanning electron microscopy and Fourier transform infrared spectroscopy analyses demonstrated changes in the surface microstructure and functional groups in FO-CRPP. Our findings suggested that yeast extract and NH4Cl significantly improve the accumulation of antioxidants in CRPP during SSF by A. niger CGMCC 3.6189.

Implementation of analytical quality by design concepts for the optimization of quantitative 1H nuclear magnetic resonance (1H-qNMR) method for quantitation of novel anti-covid drugs (molnupiravir and favipiravir) in their pharmaceutical dosage forms

For the first time in the literature, the Analytical Quality by Design (AQbD) principles were applied to the development of a specific and simple quantitative proton nuclear magnetic resonance (1H-qNMR) method for quantitation of two antiviral drugs, molnupiravir (MOL) and favipiravir (FAV). This 1H-qNMR method was developed within the QbD framework, the new paradigm of quality recently outlined in the ICH Q14 guidelines. Basic principles of AQbD have been adapted starting with early risk assessment and identification of the analytical target profile (ATP), the analytical procedure attributes (APA) and the analytical procedure parameters (APPs). During the scouting phase, dimethyl sulfoxide-d6 (DMSO‑d6) was selected as the deuterated solvent and maleic acid as the internal standard. The quantitative determination was based on the selective proton signals from MOL's pyrimidine ring at 6.82 ppm (doublet) and FAV's hydroxyl group at 8.71 ppm (singlet), as well as a singlet signal from the IS at 6.24 ppm. A Box-Behnken Design was employed in response surface methodology to develop mathematical predictive models relating the APPs to the APAs followed by multicriteria- decision making with the aid of Derringer's desirability function. Finally, the method operable design regions (MODRs) were computed with the aid of Monte Carlo simulations and identified as the multidimensional combination of the APPs where the risk of failure to fulfill the requirements for the APAs was lower than 5 %. The most robust NMR conditions for MOL, with MODR intervals in brackets, were as follows: no. of scans of 72 (16–124.4), a relaxation delay of 19.8 s (1.2–40 s) and an acquisition time of 3.98 s (2.1–6 s). Similarly, for FAV NMR quantitation, the most robust conditions were found to be 72 scans (16–117.3), a relaxation delay of 19.8 s (1.4–40 s) and an acquisition time of 3.98 s (2.2–6 s). The developed method was validated in accordance with the recently endorsed ICH Q2R2 guidelines, and it exhibited detection limits of 1.04 and 0.88 mg mL−1, as well as quantitation limits of 3.45 and 2.95 mg mL−1 for MOL and FAV, respectively. The method was successfully applied to the analysis of the studied analytes in their pharmaceutical products, proving to be simple, fast, non-destructive, and accurate. Additionally, it can be considered an environmentally friendly alternative for quantitation and quality control analysis of pharmaceutical products.

Influence of Ultrasonic and Chemical Pretreatments on Quality Attributes of Dried Pepper (Capsicum annuum).

This study investigates the effects of ultrasound, in combination with chemical pretreatments, on the quality attributes (total phenolic and carotenoid content, antioxidant activity (2,2-Diphenyl-1-picrylhydrazyl assay (DPPH)), ferric-reducing ability (FRAP), CIE L* a* b* color, non-enzymatic browning, rehydration ratio, textural and morphological properties) of red pepper subjected to drying (hot air drying or freeze drying). The fractional factorial design was used to assess the impact of factors. The global Derringer desirability function was used to determine the optimal conditions for the best quality attributes of dried pepper. The drying method influenced total phenolic content, a* (redness), and initial rehydration ratio; pretreatment time significantly affected FRAP antiradical activity, a*, chroma and non-browning index, while pH-value had a significant effect on the texture of dried pepper. Non-enzymatic browning was reduced to 72.6%, while the DPPH antioxidant capacity of freeze-dried peppers was enhanced from 4.2% to 71.9%. Ultrasonic pretreatment led to changes in the pepper morphology, while potassium metabisulfite (KMS) was a more effective additive than citric acid.

Environment-functionality-cost balance of an analytical reagent

Green chemistry was originally mainly driven by organic synthetic approaches, but green analytics is slowly following, searching for ways to reduce volumes, cost and ecotoxicity of analytically used chemicals and lowering energy usage. The emphasis is currently focussed on techniques such as miniaturization, on-line spectroscopy, or the chemicals directly used in the analytical process, e.g. chromatographic solvents. However, almost no attention has yet been paid to the analytical reagents, and more specifically, the way they are produced and used in greening analytics. In the analysis of low level analytes, such as peptides in the biomedical area, a prominent challenge is their possible adsorption to glass or plastic consumables used during analysis. In this research, a recently developed anti-adsorption diluent based on bovine serum albumin, acetonitrile and formic acid, was investigated towards greener alternatives. The 12 principles of green chemistry were applied, but also the anti-adsorption functionality and cost-efficiency were taken into account to obtain a more holistic sustainability view. A Derringer desirability function was used to convert these 3 aspects into one overall ‘fit-for-purpose’ score, from which it was concluded that replacing acetonitrile by (denatured) ethanol is the most optimal choice, whilst maintaining bovine serum albumin as protein source.

A synergistic framework for development of green HPLC methods for determination of amlodipine besylate and candesartan cilexetil in presence of their hydrolytic degradation products in two different matrices

The world is changing so fast towards rationalization of resources consumption and employing safer practices for the surrounding environment and humans. Therefore, there is a renewed interest in integrating green analytical chemistry principles and experimental design methodologies for screening and optimizing complex analytical procedures such as HPLC. Thus, this work introduces three sustainable versatile multi-analyte HPLC methods with two types of detection techniques. Firstly, amlodipine besylate and candesartan cilexetil with three of their hydrolytic products were chromatographed on CSH-C18 (150 mm) stationary phase within short run time (about 8.9 min) through gradient elution mode, flow rate 1 mL min−1 and UV-detection at 210 nm and 254 nm. Face-centered composite design and Derringer's desirability function were implemented to optimize the chromatographic conditions to fit the goals of pharmaceutical and biological analysis via fluorometric detection. A good separation was obtained utilizing HSS-Cayno (250 mm) column and mobile phase composed of ethanol and phosphate buffer, pH 3.5, (55.6: 44.4, v/v) delivered at 1.03 mL min−1 at 245 and 446 nm as excitation and emission wavelengths, respectively, with quantification range of 1.00–400.00 ng mL−1 for amlodipine and 1.00–600.00 ng mL−1 for candesartan cilexetil. The conditions were modified for plasma analysis to a new ratio (45:55, v/v) pH 3.7 and flow rate 0.7 mL min−1. The methods' greenness profiles have been evaluated and compared with the reported ones via several comprehensive tools.

Response Surface Methodology-Based Quantification of Lamivudine and Zidovudine Using Reverse-Phase High-Performance Liquid Chromatography in Pharmaceutical Formulation

Objective: A novel reverse-phase high-performance liquid chromatography (RP-HPLC) method for estimation of lamivudine and zidovudine by using an experimental design approach applying the response surface technique was developed and validated using a C18 column and its application in marketed formulation. Multivariate optimization of experimental conditions was achieved using experimental design employing organic content in the mobile phase, pH, and flow rate of the mobile phase as three independent variables. The aim of this study was to apply response surface methodology and to study the effect of the independent variables on the separation and estimation of both drugs by the RP-HPLC method using a faced central composite experimental design. Materials and Methods: Derringer's desirability function was used to optimize the retention period of the last eluting peak and peak symmetry, and it was discovered that the optimal conditions were potassium dihydrogen phosphate buffer and acetonitrile in an isocratic ratio of 55:45 w/v, pH 3.5, and 0.4 ml/min flow rate. Baseline separation of both medications with good resolution and a run time of more than 7 min was accomplished using this ideal condition. Results: For lamivudine and zidovudine, a linear response was seen over the concentration range of 2–12 and 4–24 μg/mL, respectively. Lamivudine's limit of detection and limit of quantitation were determined to be 3.08 and 9.18 μg/mL, respectively, whereas zidovudine's values were 3.24 and 10.17 μg/mL. According to the ICH guidelines acceptance criteria for linearity, accuracy, precision, specificity, and robustness, the method was successfully validated.

Dispersive Solid–Liquid Microextraction Based on the Poly(HDDA)/Graphene Sorbent Followed by ICP-MS for the Determination of Rare Earth Elements in Coal Fly Ash Leachate

A dispersive solid-phase microextraction (DSPME) sorbent consisting of poly(1,6-hexanediol diacrylate)-based polymer microspheres, with embedded graphene microparticles (poly(HDDA)/graphene), was synthesized by microfluidic emulsification/photopolymerization and characterized by optical microscopy and X-ray fluorescence spectrometry. This sorbent was applied for simple, fast, and sensitive vortex-assisted DSPME of rare earth elements (RREs) in coal fly ash (CFA) leachate, prior to their quantification by inductively coupled plasma mass spectrometry (ICP-MS). Among nine DSPME variables, the Plackett–Burman screening design (PBD), followed by the central composite optimization design (CCD) using the Derringer desirability function (D), identified the eluent type as the most influencing DSPME variable. The optimum conditions with maximum D (0.65) for the chelating agent di-(2-ethylhexyl) phosphoric acid (D2EHPA) amount, the sorbent amount, the eluting solvent, the extraction temperature, the centrifuge speed, the vortexing time, the elution time, the centrifugation time, and pH, were set to 60 μL, 30 mg, 2 M HNO3, 25 °C, 6000 rpm, 1 min, 1 min, 5 min, and 4.2, respectively. Analytical validation of the DSPME method for 16 REEs (Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) in CFA leachate samples estimated the detection limits at the low ppt level, the recovery range 43–112%, and relative standard deviation within ± 22%. This method was applied to a water extraction procedure (EP) and acetic acid toxicity characteristic leaching procedure (TCLP) for leachate of CFA, from five different coal-fired thermoelectric power plants. The most abundant REEs in leachate (20 ÷ 1 solid-to-liquid ratio) are Ce, Y, and La, which were found in the range of 22–194 ng/L, 35–105 ng/L, 48–95 ng/L, and 9.6–51 μg/L, 7.3–22 μg/L, 2.4–17 μg/L, for EP and TCLP leachate, respectively. The least present REE in TCLP leachate was Lu (42–125 ng/L), which was not detected in EP leachate.

A simple method for glass analysis using total reflection X-ray fluorescence spectrometry

In this work, a simple and cost-effective method was developed for Na, Mg, Al, K, Ca, Ti, V, Cr, Mn, Ni, Cu, Zn, Rb, Sr, Ba and Pb determination in glass samples employing suspension sampling and total reflection X-ray fluorescence (TXRF). The experimental conditions were optimized using multivariate approach being the optimum conditions located by Derringer's desirability function. Proposed method was validated in accordance with the National Institute of Metrology, Quality and Technology (Inmetro, Brazil). Limit of detection (LD) and limit of quantification (LQ) were adequate for determination of trace elements in glass. The evaluation of the accuracy and precision was realized by analysis of standard reference materials of glass (NIST 612). For the majority of the elements, good agreement was achieved between the certified value and the value obtained in the NIST 612. The relative standard deviation (RSD%) was achieved between 3.6 and 10.3%. Moreover, no significant differences were observed between the proposed method compared to the ICP-MS. After the validation step, the method was applied to 31 glass samples and with aid of an exploratory principal component analysis (PCA), a perfect discrimination of the glass from originally manufactured smartphones was obtained. In addition, soda-lime glass could be reasonably distinguished from smartphone screens. The developed method is fast, consumes low amounts of reagents and allows the determination of many analytes simultaneously. Additionally, the method does not require calibration curves. Therefore, TXRF proved to be attractive and useful for routine analysis of glass.

Analysis of short-chain bioactive peptides by unified chromatography-electrospray ionization mass spectrometry. Part I. Method development

A method to analyse short-chain bioactive peptides (MW < 800 Da) and their impurities was developed with a unified chromatography (UC) analysis, including a wide mobile phase gradient ranging from supercritical fluid to near-liquid conditions, with UV and electrospray ionization mass spectrometry detection (ESI-MS). Four stationary phases and three mobile phase compositions were examined. Ten model peptides were first selected to identify the best operating conditions, including five linear tripeptides and five cyclic pentapeptides, with log P values ranging from -5.9 to 3.6, and including isomeric species. Derringer desirability functions were designed to identify optimal operating conditions based on 7 criteria, namely the number of peaks detected (including all impurities resolved), the proportion of the chromatogram occupied by target peaks, the least favourable resolution observed between the main peptide and impurities, peak shape features (asymmetry and peak width at half height), and finally the signal-to-noise ratio observed both with UV (210 nm) and ESI-MS in positive ionization mode.The optimum conditions were obtained on Ascentis Express OH5 stationary phase, with a mobile phase composed of carbon dioxide and methanol, comprising 2% water and 20 mM ammonium hydroxide. The final gradient program ranged from 5 to 80% co-solvent in CO2, with a reversed flow rate gradient ranging from 3.0 to 1.5 mL/min. Back-pressure was set at 120 bar and the column oven temperature at 60°C. Optimal conditions were applied to a large set of 76 peptides (34 linear tripeptides and 42 cyclic pentapeptides) and provided adequate scattering of the peaks in the retention space, together with some separation of isomeric species, particularly for the cyclic peptides.

Design of experiments in optimization and validation of hydrophilic interaction liquid chromatography method for determination of amlodipine besylate and its impurities

Abstract A new and rapid hydrophilic interaction liquid chromatographic method has been developed for the quantitative analysis of amlodipine besylate and its specific impurities (D, E, and F). For development of this method, a systematic approach which includes Design of Experiments methodology was applied. For the method optimization, Box–Behnken design and specific way Derringer's desirability function were applied. They provided identification of the optimal chromatographic conditions on the basis of obtained mathematical models and graphical procedures (three D graphs). The optimal chromatographic conditions were the analytical column ZORBAX NH2 (250 × 4.6 mm, 5 µm particle size); mobile phase consisted of acetonitrile-water phase (50 mM ammonium acetate, pH adjusted to 4.0 with glacial acetic acid) (90.5:9.5 v/v); column temperature 30 °C, mobile phase flow rate 1 mL min−1, wavelength of detection 230 nm. As other validation parameters were also found to be suitable, the possibility to apply the proposed method for the determination of amlodipine besylate and its impurities in any laboratory under different circumstances has been proven.

Effects of high volume dolomite sludge on the properties of eco-efficient lightweight concrete: Microstructure, statistical modeling, multi-attribute optimization through Derringer's desirability function, and life cycle assessment

Micro fines stone sludge (μSS) as dolomite, is a hazardous waste and creates many health problems along with air, water and land pollution. The research paper presents the statistical models with the help of response surface methodology, aiming to develop μSS incorporated structural grade lightweight cellular concrete (SG- LCC) using novel mix design (with 15 design steps). The three level-three factorial (33) Box Behnken Design was employed to investigate the effects of three input parameters i.e. temperature of water to be diluted with surfactant (Tw), flowability value (FV) and percentage replacement of μSS (%RμSS) on all the dependent responses i.e. oven dry density (ρOD), uniaxial compressive strength (fc.28d), performance factor for uniaxial compressive strength (PFc.28d) and thermal conductivity (λ-value). The regression analysis and Derringer's desired function methodology was applied to find out an optimum condition for developing SG-LCC (as replacement of masonry brick) containing maximum volume of wet μSS. It was finally concluded that by optimizing above sensitive input parameters, eco-efficient SG-LCC can be produced at Tw of 31°C, %RμSS of 51.50% and FV of 135.50%.The developed SG-LCC have ρOD of 1243 kg/m3, fc.28d of 8.23 MPa, PFc.28 of 6621 Pa/(kg/m3) and λ-value of 0.456 W/mK. Microstructure studies indicated that μSS filers does not participate chemically in cement hydration reactions. However, these filers imparted physical effect by acting as nucleation sites for the cement hydration products. The economic index was 18.42% higher for the final optimized mix, than that of the control mix. Use of wet μSS (up to 51%) to produce optimized SG-LCC mix, will not only reduce the production cost up to 17.54%, but also it will conserve natural RS and tap water by 26.28% and 100%, respectively. Life cycle assessment also showed that production of SG-LCC containing higher amount of μSS; consumes lower energy, and emits lesser amount of greenhouse gases that are the key parameters requirements for sustainable development goals.

Eco-friendly chiral HPLC method for determination of alfuzosin enantiomers and solifenacin in their newly pharmaceutical combination: Method optimization via central composite design

The high abundance and advantages of polysaccharides make them among the most widely used chiral stationary phases in liquid chromatography. However, extended analysis time and consumption of toxic organic solvents, associated with traditional columns, remain the main stumbling blocks of such methods’ sustainability. A new green chiral HPLC-separation, with just 0.45 mL ethanol in mobile phase per run utilizing a 50-mm column as a stationary phase, achieves a significant determination of alfuzosin (ALF) enantiomers along with solifenacin (SOL) simultaneously. Enantioseparation of ALF was firstly evaluated in the reversed-phase mode using five polysaccharide-based Lux columns (Amylose 2 and Cellulose 1–4), highlighting Lux Cellulose 2 to reach the best enantioselectivity. Central composite design with Derringer's desirability function was then adopted to optimize the chromatographic conditions for an acceptable resolution. A mobile phase composed of ethanol and phosphate buffer, pH 4, (30:70, v/v) at a rate of 0.5 mL/min with UV-detection at 215 nm, exhibits good separation of ALF-enantiomers from SOL with resolution values of 1.45 and 2.64, respectively. The method’s greenness profile has been assessed and compared with that of mostly reported ones via the newest comprehensive analytical method greenness score (AMGS) calculator. The proposed method is considered a straightforward approach towards safer, more economic, eco-friendly and comparatively favorable for the cited drugs’ quantification in their formulation.

HPLC method development for determination of metoprolol, telmisartan and cilnidipine simultaneously using response surface design

The development of an HPLC method for determination of Metoprolol, Telmisartan and Cilnidipine simultaneously in additional dosage was not published or reported up till date. The main aim of our study was to design a simultaneous and multiple response optimizations using the Derringer's desirability function in order to estimate Metoprolol, Telmisartan and Cilnidipine in pharmaceutical and bulk drug dosage form by HPLC method with experiment central compositive design (CCD) protocol for the quantitative methods analysis and also for validation of the procedure that is developed as per ICH regulations. An innovative RP-HPLC method had been designed for the estimation of Metoprolol, Telmisartan and Cilnidipine simultaneously in formulation using central composite design. Three factors were investigated and determined as significant when compared to the interaction and quadratic effect of the samples that CCD along with the response of the surface methodology. The developed method produced a good resolution of the drugs with a very short run time of 7.5 min. It was also validated according to ICH guidelines. It was recognized as novel and simple method that is accurate and cost-effective. So the proposed method fits best in the assaying routine of Metoprolol, Telmisartan and Cilnidipine in any formulations produced by quality control laboratories.

Optimizing homogenizer-assisted extraction of chlorophylls from plantain epicarp (Musa paradisiaca L.)

The objective of this study was to establish parameters of optimization of the factors such as solid/solvent ratio, stirring speed and extraction time in homogenizer-assisted extraction (HAE) of chlorophyll a, b and total from plantain epicarp (Musa paradisiaca L.) using the Box–Benhken design. The individual effect and the interactions of the process variables (solid/solvent ratio, stirring speed (revolutions per minute, rpm), and extraction time in HAE) on the chlorophyll a, b and total contents in the extract were studied. The optimization was carried out with a Derringer desirability function, and it was found that the optimal extraction conditions included a solid/solvent ratio of 0.025 g/mL, an stirring speed of 13,508 and 90 s of treatment with Ultra-turrax. The corresponding predicted values were 33.67 mg/100 g of chlorophyll a, 32.915 mg/100 g of chlorophyll b and 66.585 mg/100 g of total chlorophyll. Finally, the optimal conditions were experimentally verified, and it was established that extraction with an Ultra-Turrax treatment is more efficient than the conventional method (maceration).

A biological-based adsorbent for a non-biodegradable pollutant: Modeling and optimization of Pb (II) remediation using GO-CS-Fe3O4-EDTA nanocomposite

A new graphene oxide (GO)-derivative nanocomposite containing biological polymer (i.e. chitosan) was successfully fabricated and investigated for Pb (II) adsorption from aqueous solutions. The nanocomposite (NC) performance was evaluated under different conditions of adsorbent dose (1–18.51 mg), Pb (II) initial concentration (0.35–33.65 mg/L), pH (1.24–10.76), temperature (~ 28–52 °C), and time (~ 2.5–23 min). The process was modeled by the methods of CCD, ANFIS, and GRNN and optimized by the approaches of Derringer's desirability function (DF) and genetic algorithm (GA). Although all models indicated good predictions, ANFIS showed the best function (with R2 0.9998, RMSE 0.0026, MAE 0.0016, and AAD 0.0023) in modeling of Pb (II) adsorption by GO-Fe3O4-CS-EDTA NC. Moreover, GA resulted the following optimum conditions: adsorbent dose 9.50 mg, initial Pb (II) concentration 24.00 mg/L, pH 8.00, tempreature 49.32°C, and time 22.20 min in which 93.98% Pb (II) predicted to be removed. And a maximum adsorption capacity of 666.66 mg/g was calculated by the Langmuir model (R2 = 0.937) that was much higher than that of stated by using the recently developed adsorbents for Pb (II). The enthalpy changes (ΔH°) of −21.62 to −26.65, Gibbs free energy (ΔG°) of 15.90, and entropy changes (ΔS°) of 0.1259 revealed an endothermic and spontaneous nature of the process. The elimination of Pb (II) followed a pseudo second-order kinetic model (R2 = 0. 9437). The influence of co-existing ions on the adsorption of Pb (II) showed a negative significant effect (of 93% to 75%) only at high mixture concentration (> 10 mg/L).All in all, the high removal efficiency and adsorption capacity, selectivity, reusability (six times without significant breakthrough), and working in a normal pH value, make GO-Fe3O4-CS-EDTA NC as a potential adsorbent for in situ treatment of lead ions-containing aqueous solutions.

Chemometric assisted UV spectrophotometric and RP-HPLC methods for simultaneous determination of paracetamol, diphenhydramine, caffeine and phenylephrine in tablet dosage form.

In this paper, Chemometric assisted UV spectrophotometric and RP-HPLC methods were developed and compared for simultaneous determination of Paracetamol, Diphenhydramine Hydrochloride, Caffeine and Phenylephrine Hydrochloride in tablet dosage form. UV-Spectrophotometric analysis was carried out by applying two chemometric models namely, Principal Component Regression method (PCR) and Partial Least Squares Regression method (PLSR). Chromatographic method was developed and optimized by applying Response surface methodology -Central Composite Design (CCD). These methods were considered first for the quantification of the drugs present in the selected formulation. PCR and PLSR models were successfully validated and applied for resolving the complex UV-spectra in the wavelength range of 240-320nm with a data interval of 1nm. In RP-HPLC method, the identified critical factors were methanol content (45-55% v/v) and flow rate (0.75-0.85mL/min) and the selected responses were retention time (Rt4) of fourth eluted component and resolution (RS1,2) between first and second eluted components. Derringer's desirability function was used for the optimization of the chromatographic method conditions which comprised of mobile phase consisting of methanol‑potassium dihydrogen orthophosphate buffer (pH3; 10mM) (50: 50, v/v) and at a flow rate of 0.81mL/min with a detection wavelength of 220nm. One-way ANOVA in 95% confidence interval revealed that there were no significant differences among the developed methods.

Box-Behnken Design-Desirability Function Approach in Optimization of HPLC Method for Simultaneous Determination of Ibuprofen Along with Additives in Syrup Formulation.

The advantages of simultaneous analyses are a decrease in analysis time and a more economical use of solvents and reagents. It is desirable that HPLC analyses possess both short term and good resolution. The aim of the current study is to develop an HPLC method for the simultaneous determination of ibuprofen, sodium benzoate, methyl paraben and propyl paraben as preservatives, and sunset yellow as a colorant, in syrup formulation. To optimize chromatographic separation conditions, multi-response optimization using the Derringer's desirability function was employed for the development of a rapid and efficient HPLC method. The ranges of independent variables used for the optimization process were 50-60% (v/v) for acetonitrile, 5.0-7.0 for pH, and 1.0-2.0 mL/min for flow rate of the mobile phase. The effects of these variables on the output responses, such as critical resolution between sunset yellow and sodium benzoate and retention time of the last peak indicating analysis time of the method, were evaluated by statistical experimental design. Optimum conditions fixed for the simultaneous analyses were acetonitrile:phosphate buffer (60:40, v/v), pH 5.0, and a flow rate of 1.8 mL/min. The eluate was monitored using a photo diode detector set at 220 nm. Total chromatographic analysis time was approximately 3 min. The developed method validated as per International Conference on Harmonization guidelines was successfully applied for the determination of five compounds in their pharmaceutical formulation. This efficient method has isocratic elution system and can be used for routine analyses of these compounds in similar pharmaceutical products.

Combining chemometrics and the technique for the order of preference by similarity to ideal solution: A new approach to multiple-response optimization of HPLC compared to desirability function

Some devices are used in the pharmaceutical industry to produce and control the quality of a variety of pharmaceutical products; therefore, it would be helpful to identify the factors affecting the performance of the devices and optimize them in terms of time and cost. In this regard, the use of experimental design approaches to optimization is important as it can help a device achieve its highest efficiency. One of the most popular devices in the pharmaceutical industry is high-performance liquid chromatography (HPLC). In view of its wide use in the industry and the number of factors affecting it, it is necessary to design and validate a new method that can simultaneously optimize its different parameters. In this study, the method of the simultaneous optimization of the parameters was implemented using the Box-Behnken design and multiple-criteria decision-making (MCDM) by Derringer's desirability function and technique for the Order of Preference by Similarity to Ideal Solution (TOPSIS) method. In this regard, mobile phase ratio, flow rate, and pH were simultaneously changed, and capacity factor, total analysis time, and resolution were considered as responses. To validate the method, the key parameters of the method were determined and used for all the validation steps. Therefore, this approach to optimizing HPLC factors is new and very cost-effective with diverse applications in the pharmaceutical industry.