Multiobjective optimization strategy based on desirability functions used for the microemulsion liquid chromatographic separation and quantification of norfloxacin and tinidazole in plasma and formulations.

The aim of the present study was to optimize a microemulsion liquid chromatography method for the simultaneous determination of norfloxacin and tinidazole binary mixture using a chemometric protocol. Optimization experiments were conducted through a process of screening and optimization. A 2(7-4) fractional factorial design was used as screening design. While the location of optimum conditions was established by applying Derringer's desirability function. The optimal mobile phase composition was predicted to be: 3.5% w/v SDS, 10.03% v/v 1-propanol, 0.5% v/v 1-octanol, and 0.3% triethylamine in 0.02 M phosphoric acid at pH 6.5. The mobile phase was delivered isocratically at a flow rate of 1 mL/min with UV detection at 290 nm. Tinidazole and norfloxacin were eluted with retention times of 1.8 and 5.8 min, respectively. The calibration plots displayed good linear relationships in the concentration ranges of 0.5-50 and 0.75-75 µg/mL for norfloxacin and tinidazole, respectively. The method was successfully applied for determination of both drugs in pharmaceutical dosage forms and real human plasma. Where the accuracy was proved by the low values of % error and high values of recovery, also the relative standard deviation for the results did not exceed 1.5%, proving the precision of the method.

Separation optimization of aniline and seven 4-substituted anilines in high-submicellar liquid chromatography using empirical retention modeling and Derringer's desirability function.

The separation optimization of aniline and seven 4-substituted derivatives in high-submicellar LC was performed using an interpretive optimization strategy and Derringer's desirability function. Description of the retention of solutes was carried out through several hyperbolic and logarithmic retention models using the retention data of five mobile phases of SDS (0.06-0.12 M) and methanol (50-70% v/v) at pH 3. Among the investigated models, a logarithmic retention model logk=c0+c1φ+c2[S]+c12φ[S]+d12(φ[S])0.5 showed the best prediction capability and was used to predict the solute retention factors. A grid search program was used to calculate the retention times of each solute, based on the best retention model, for all combinations of SDS and methanol concentrations in the factor space. Two different chromatographic goals, analysis time and retention differences between adjacent peaks, were evaluated simultaneously using Derringer's desirability function for each mobile phase conditions in the grid search. Optimal mobile phase composition for separation of eight anilines was found to be 0.119 M SDS and 53% v/v methanol. Under these conditions, full resolutions with a reasonable analysis time (22 min) were obtained. At the optimal condition, a good agreement was observed between predicted and experimental values of the retention times.

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.

In depth investigation of the retention behavior of structurally related ß-blockers on RP-HPLC column: Quality by design and quantitative structure-property relationship complementary approaches for optimization and validation.

The persistent introduction of new ß-blockers motivates the demand for optimizing RP-HPLC well-designed analytical procedures that could be applied to this structurally related and commonly prescribed pharmacological group in order to reduce time and chemicals consumption in quality control units. Betoxolol HCl (BEX) and Carvidolol (CAR) were selected as representative examples to conduct predictive studies based on two complementary approaches, Quality by design (QBD) and Quantitative structure property relationship (QSPR). In concern QBD, a Box-Behnken design was adopted at variable chromatographic parameters to achieve the most proper conditions that might be applied for efficient analysis of the majority of group members. On the other hand, the retention time was chosen as the target property in the QSPR study that was conducted onto seven ß. blockers (the two investigated drugs in addition to five other ß. blockers) to find the best correlated molecular descriptors to the retention behavior. Both external and internal validation studies have comparable quality with training levels. Hence a simple selection algorithm of conventional features provides robust confirmatory predictive QBD and QSPR models. Derringer's desirability function as as a multi-criteria approach was applied for getting the optimum chromatographic analysis conditions. Efficient analysis of BET and CAR was achieved at column temperatures of 26.00 and 27.50 °C, respectively using acetonitrile and phosphate buffer (pH 4.55) 70:30 v/v as a mobile phase with a flow rate of 1.00 mL/min, and UV detection at 220 nm. The method was validated in accordance to ICH guidelines, and had exhibited acceptable precision, accuracy, linearity, and robustness.

Simplex-centroid design and Derringer's desirability function approach for simultaneous separation of phenolic compounds from Mimosa scabrella Bentham honeydew honeys by HPLC/DAD.

Honeydew honeys have been under-evaluated about their major phenolic compounds, especially Mimosa scabrella Bentham (bracatinga) honeydew honey. In this work, a fast and robust chromatographic method was optimized for simultaneous separation and quantification by HPLC/DAD of 18 phenolic compounds detected in bracatinga honeydew honey. A simplex-centroid design, central composite rotatable design and response surface-desirability function simultaneous optimization of Derringer and Suich were used, evaluating the mobile phase composition, flow rate and oven temperature to separate all the peaks. These multivariate procedures were efficient in determining the optimal separation conditions, using peak pair resolutions and run time as responses. The 18 peaks were separated in 25 min and the mobile phase gradient started with 1.6% MeOH, 3.3% ACN, 1.0% THF and 94.1% formic acid 0.1% changing to 10.0% MeOH, 33.3% ACN, 6.0% THF and 50.7% formic acid 0.1%, oven temperature of 33 °C and flow rate of 0.73 mL min-1. The method was validated according to Eurachem guidelines and considered accurate and robust. It was applied to 18 bracatinga honeydew honey samples in which 9 phenolic compounds were identified and quantified.

Doehlert design-desirability function multi-criteria optimal separation of 17 phenolic compounds from extra-virgin olive oil by capillary zone electrophoresis.

In Brazil, the consumption of extra-virgin olive oil (EVOO) is increasing annually, but there are no experimental studies concerning the phenolic compound contents of commercial EVOO. The aim of this work was to optimise the separation of 17 phenolic compounds already detected in EVOO. A Doehlert matrix experimental design was used, evaluating the effects of pH and electrolyte concentration. Resolution, runtime and migration time relative standard deviation values were evaluated. Derringer's desirability function was used to simultaneously optimise all 37 responses. The 17 peaks were separated in 19min using a fused-silica capillary (50µm internal diameter, 72cm of effective length) with an extended light path and 101.3mmolL(-1) of boric acid electrolyte (pH 9.15, 30kV). The method was validated and applied to 15 EVOO samples found in Brazilian supermarkets.

Derringer desirability and kinetic plot LC-column comparison approach for MS-compatible lipopeptide analysis.

Lipopeptides are currently re-emerging as an interesting subgroup in the peptide research field, having historical applications as antibacterial and antifungal agents and new potential applications as antiviral, antitumor, immune-modulating and cell-penetrating compounds. However, due to their specific structure, chromatographic analysis often requires special buffer systems or the use of trifluoroacetic acid, limiting mass spectrometry detection. Therefore, we used a traditional aqueous/acetonitrile based gradient system, containing 0.1% (m/v) formic acid, to separate four pharmaceutically relevant lipopeptides (polymyxin B1, caspofungin, daptomycin and gramicidin A1), which were selected based upon hierarchical cluster analysis (HCA) and principal component analysis (PCA). In total, the performance of four different C18 columns, including one UPLC column, were evaluated using two parallel approaches. First, a Derringer desirability function was used, whereby six single and multiple chromatographic response values were rescaled into one overall D-value per column. Using this approach, the YMC Pack Pro C18 column was ranked as the best column for general MS-compatible lipopeptide separation. Secondly, the kinetic plot approach was used to compare the different columns at different flow rate ranges. As the optimal kinetic column performance is obtained at its maximal pressure, the length elongation factor λ (Pmax/Pexp) was used to transform the obtained experimental data (retention times and peak capacities) and construct kinetic performance limit (KPL) curves, allowing a direct visual and unbiased comparison of the selected columns, whereby the YMC Triart C18 UPLC and ACE C18 columns performed as best. Finally, differences in column performance and the (dis)advantages of both approaches are discussed.