Development of a Validated Stability-Indicating HPLC Method for Vinpocetine in the Presence of Potential Impurities in Tablet Dosage Form by Multiresponse Optimization.

BACKGROUND: Vinpocetine has been prescribed for the treatment of ischemic brain diseases for many years. The drug, which has side effects such as headache, flushing, and decreased blood pressure, is not found in nature, but it can be synthesized by several approaches. OBJECTIVE: A simple, rapid, selective, stability-indicating high-performance liquid chromatographic (HPLC) method was developed for the simultaneous estimation of vinpocetine and their potential impurities in a tablet formulation. METHOD: Optimum HPLC conditions were tried to be determined by a statistical experimental design method. The proposed method was validated as per the ICH guidelines. Stress study was used to demonstrate the stability-indicating ability of the developed method in the quantification of vinpocetine and potential impurities within the same run. RESULTS: According to multiresponse optimization using the Derringer's desirability function, the mobile phase consisted of an acetonitrile-phosphate buffer (pH 6.0) in the ratio of 65:35 (v/v) at a flow rate of 1.7 mL/min. Significant degradations were observed for the drug product under acid hydrolysis and alkali hydrolysis. The new method showed reasonable detection and quantification limits with good selectivity, precision, linearity, and recovery. CONCLUSIONS: These validation results have shown that this method is suitable for quantitative determination of vinpocetine and its impurities in quality control laboratories. HIGHLIGHTS: A reliable and rapid HPLC method optimized with response surface methodology and multiresponse optimization based on Derringer's desirability function was developed for the simultaneous analysis of vinpocetine and its impurities in a tablet formulation.

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

BACKGROUND: 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. OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: The developed method validated as per International Conference on Harmonization guidelines was successfully applied for the determination of five compounds in their pharmaceutical formulation. HIGHLIGHTS: This efficient method has isocratic elution system and can be used for routine analyses of these compounds in similar pharmaceutical products.

Quantitative Analysis of Food Additives in a Beverage using High Performance Liquid Chromatography and Diode Array Detection Coupled with Chemometrics.

BACKGROUND: In many countries, the levels of synthetic food additives causing harm to humans have been determined and their use has been controlled by legal regulations. Sensitive, accurate and low-cost analysis methods are required for food additive determination. OBJECTIVE: In this study, a fast high performance liquid chromatography-diode array detection (HPLC-DAD) analytical methodology for quantification of sodium benzoate, potassium sorbate, ponceau 4R, and carmoisine in a beverage was proposed. METHODS: Partial least squares (PLS) and principal component regression (PCR) multivariate calibration methods applied to chromatograms with overlapped peaks were used to establish a green and smart method with short isocratic elution. A series of synthetic solutions including different concentrations of analytes were used to test the prediction ability of the developed methods. CONCLUSIONS: The average recoveries for all target analytes were in the range of 98.27-101.37% with average relative prediction errors of less than 3%. The proposed chemometrics-assisted HPLC-DAD methods were implemented to a beverage successfully. Analysis results from sodium benzoate, potassium sorbate, ponceau 4R, and carmoisine in a beverage by PLS-2 and PCR were statistically compared with conventional HPLC. HIGHLIGHTS: The HPLC methods coupled with the PLS-2 and PCR algorithm could provide a simple, quick and accurate strategy for simultaneous determination of sodium benzoate, potassium sorbate, ponceau 4R, and carmoisine in a beverage sample.

Multivariate optimization of a new LC-MS/MS method for the determination of 156 pesticide residues in milk and dairy products.

BACKGROUND: Pesticides are widely utilized worldwide to control undesirable life forms during the planting procedure in agriculture. But they can pollute the nature and jeopardize human wellbeing. Additionally, on account of high resistance and biological activity; pesticides are able to accumulate in living organs and lead to acute and long-term negative effects along with toxicity. Milk and dairy products constitute an important part of a humans' diet since they contain fundamental supplements and nutrients, however they may also be the source of unhealthy components including pesticides. Therefore efficient, accurate and sensitive determination methods must be improved to quantify pesticide residues in these food samples. RESULTS: Multivariate optimization strategy was employed to optimize an efficient and robust liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for the determination of 156 pesticide residues in milk and dairy products. Three independent variables considered and their levels in the Box-Behnken design were as follows: initial percentage of eluent A in mobile phase (30, 40, 50%), flow rate of the mobile phase (0.1, 0.2, 0.3 mL min-1 ), and ammonium formate concentration in mobile phase (0.0, 0.5, 1.0 mmol L-1 ). Under optimized conditions, average recoveries of target analytes were obtained in the range of 70.38% to 119.04%. Detection and quantification limits ranged from 0.06 to 2.70 µg kg-1 and from 0.22 to 8.10 µg kg-1 , respectively. CONCLUSION: The validated method was successfully implemented to the analysis of 20 milk and dairy products including cream, cheese and yogurt. This method could be applied in many laboratories to reduce analysis time and cost. © 2020 Society of Chemical Industry.

Integrating molecularly imprinted polymer beads in graphite-epoxy electrodes for the voltammetric biosensing of histamine in wines.

This manuscript presents a voltammetric biosensing study with use of molecularly imprinted polymers to detect histamine in wine. Polymer beads were synthesized by standard precipitation polymerization method and implemented on the electrode surface via sol-gel immobilization. Scanning and confocal microscopy examinations permitted characterizing the material. Adsorptive stripping voltammetry in differential mode was the technique chosen for final application, selecting an enrichment time of 5 min. These conditions permitted a limit of detection of 0.19 µg mL-1 (1.0 µM), with a linear response range from 0.5 to 6.0 µg mL-1 (2.71-32.4 µM). The repeatability of the measurements was 4.6% relative standard deviation (n = 12). Principal component analysis showed the ability of the prepared receptor for discriminating other biogenic amines and potential interfering species. A final application, illustrating the determination of histamine, was completed to show agreement of results between the fluorimetric reference method and the proposed electrochemical approach.

Experimental Design Approach to Optimize HPLC Separation of Active Ingredients, Preservatives, and Colorants in Syrup Formulation.

Background: Preservatives and colorants in pharmaceutical products may be highly toxic, especially for sensitive individuals, when they are used in excessive amounts. In this context, sensitive and non-labor-intensive analytical methods with short analysis time for simultaneous quantification of these additive substances in drugs can meet all requirements in quality control laboratories. Objective: The aim of the study was to develop a simultaneous HPLC method for the analysis of pseudoephedrine HCl and guaifenesin, along with preservatives, methyl paraben and propyl paraben, and colorants, ponceau 4R and sunset yellow, in a syrup sample. Methods: Optimum conditions of HPLC separation were determined by Box-Behnken experimental design. Four independent variables of the separation were pH (6.0, 6.5, and 7.0) and flow rate of the mobile phase (2.0, 2.2, and 2.4 mL/min) and mobile phase ratios for the first and second gradient elutions (75, 80, and 85% for Gradient 1 and 50, 55, and 60% for Gradient 2 in terms of phosphate buffer percent, respectively). Results: The optimum conditions were found to be pH, 6.3; flow rate, 2.4 mL/min; and mobile phase ratios (phosphate buffer-acetonitrile) for Gradient 1 and 2, 85+15 (v/v) and 60+40 (v/v), respectively. Conclusions: Simultaneous analysis of all compounds was achieved by using this HPLC method with a short run time below 10 min. Highlights: This simple, rapid, and validated method is convenient and applicable for routine analysis of pharmaceutical products having similar composition without the need for any extraction step.

Simultaneous Determination of Potassium Sorbate, Sodium Benzoate, Quinoline Yellow and Sunset Yellow in Lemonades and Lemon Sauces by HPLC Using Experimental Design.

In this study, development and validation of a HPLC method was described for simultaneous determination of potassium sorbate, sodium benzoate, quinoline yellow and sunset yellow. A Box-Behnken design using three variables at three levels was employed to determine the optimum conditions of chromatographic separation: pH of mobile phase, 6.0-7.0; flow rate, 0.8-1.2 mL min(-1) and the ratio of mobile phase composed of a 0.025 M sodium acetate/acetic acid buffer, 80-90%. Resolution was chosen as a response. The optimized method was validated for linearity, the limits of detection and quantification, accuracy, precision and stability. All the validation parameters were within the acceptance range. The applicability of the developed method to the determination of these food additives in commercial lemonade and lemon sauce samples was successfully demonstrated.

Development and Validation of HPLC Method for the Simultaneous Determination of Five Food Additives and Caffeine in Soft Drinks.

Box-Behnken design was applied to optimize high performance liquid chromatography (HPLC) conditions for the simultaneous determination of potassium sorbate, sodium benzoate, carmoisine, allura red, ponceau 4R, and caffeine in commercial soft drinks. The experimental variables chosen were pH (6.0-7.0), flow rate (1.0-1.4 mL/min), and mobile phase ratio (85-95% acetate buffer). Resolution values of all peak pairs were used as a response. Stationary phase was Inertsil OctaDecylSilane- (ODS-) 3V reverse phase column (250 × 4.6 mm, 5 µm) dimensions. The detection was performed at 230 nm. Optimal values were found 6.0 pH, 1.0 mL/min flow rate, and 95% mobile phase ratio for the method which was validated by calculating the linearity (r (2) > 0.9962), accuracy (recoveries ≥ 95.75%), precision (intraday variation ≤ 1.923%, interday variation ≤ 1.950%), limits of detection (LODs), and limits of quantification (LOQs) parameters. LODs and LOQs for analytes were in the range of 0.10-0.19 µg/mL and 0.33-0.63 µg/mL, respectively. The proposed method was applied successfully for the simultaneous determination of the mixtures of five food additives and caffeine in soft drinks.