Development and Evaluation of Chemometric Models for the Estimation of Sumatriptan in the Presence of Naproxen and a Degradation Product Using UV Spectrophotometry.

BACKGROUND: Chemometrics is a discipline that allows the spectral resolution of drugs in a pharmaceutical formulation along with degradation product and it is as an alternative to chromatographic methods. OBJECTIVE: Sumatriptan (SUM) is co-formulated with naproxen (NAP) and used in acute migraine attacks. SUM which has physiological importance has not been subjected to any stability-indicating chemometric approaches yet so there is a need for accurate and safe method for the assay of the cited drug in their preparation. SUM was determined in pharmaceutical formulation along with NAP and in presence of alkali-induced degradation product with simple and cost-effective multivariate approaches using spectrophotometric data. The greenness and blueness assessment was applied using different ecological metrics, including green analytical procedure index (GAPI), analytical greenness metric (AGREE), analytical eco-scale (AES) & new "blueness" evaluation using BAGI tool, respectively. METHODS: Three chemometric approaches were applied for the stability-indicating determination of SUM in presence of NAP. Classical least squares (CLS), Partial least squares (PLS) and Principal components regression (PCR), three multivariate calibration numerical models that were performed on the UV- spectra of the mixtures, were used to achieve the best resolution. RESULTS: Sumatriptan was analyzed with mean accuracies for PLS (100.29 ± 1.318) and for PCR (100.60 ± 1.564). The presented methods were compared and validated for their quantitative analyses. Moreover, statistical comparison between the results obtained by the proposed models and the official methods showed no significant differences. CONCLUSION: The proposed multivariate calibrations were accurate and specific for quantitative analysis of the studied component. PLS is the best method that has the capacity for qualitative analysis of SUM and it is suitable for routine analysis and stability studies of it in quality control laboratories. Various ecological assessment metrics confirmed the long-standing eco-friendliness of the suggested models.

Enhancing the Sustainability of Eco-friendly Potentiometric Ion Selective Electrodes for Stability-Indicating Measurement of Ethamsylate: Application in Bulk and Pharmaceutical Formulations.

BACKGROUND: Through the use of sustainable and green chemistry concepts, scientists need to decrease waste, conserve energy, and develop safe substitutes for hazardous compounds, all for protecting and benefiting society and the environment. OBJECTIVE: Four novel eco-friendly ion selective electrodes (ISE) were created to determine Ethamsylate (ETM) in bulk powder and different pharmaceutical formulations. The present electrodes were fabricated and evaluated to clearly distinguish ETM from a variety of inorganic, organic ions, sugars, some common drug excipients and the degradation product, hydroquinone (HQ) of ETM, and thus could be used for stability-indicating methods. METHODS: The electrodes fabrication was based on 2-nitrophenyl octyl ether (NPOE) that was employed as a plasticizer in electrodes 1, 2, and 3 within a polymeric matrix of polyvinyl chloride (PVC) except for electrode 4, in which dibutyl sebacate was used as a plasticizer. Electrodes 1 & 2 were fabricated using tetra dodecyl ammonium bromide as an anionic exchanger and adding 4-sulfocalix-8-arene as an ionophore only to electrode 2, but electrode 1 prepared without incorporation of an ionophore. The fabrication of electrodes 3 & 4 was based on ethamsylate-tetraphenylborate (ETM-TPB) as an ion-association complex in a PVC matrix. The environmental sustainability was assessed using Green Analytical Procedure Index (GAPI), and Analytical Greenness Metric for Sample Preparation (AGREEprep). RESULTS: Electrodes 1 & 2 had linear dynamic ranges of (10-1-10 -5) and (10-1-10 -4) respectively, with a Nernstian slope of 49.6 and 53.2 mV/decade, respectively. Electrodes 3 & 4 had linear dynamic ranges of (10-1-10 -4), with a Nernstian slope of 43.9 and 40.2 mV/decade, respectively. CONCLUSION: The generated electrodes' selectivity coefficients showed good selectivity for ETM. The utility 4-sulfocalix-8-arene as ionophore had a significant influence on increasing the membrane sensitivity and selectivity of electrode 2 compared to other electrodes.

A high-throughput UPLC-MS-MS Bio-analytical method for the analysis of veterinary pharmaceutical residues in Chicken Tissues, Application of efficient-valid-green (EVG) Framework as a Competence Tool.

Antibacterial medications are receiving the most attention due to hypersensitivity reactions and the emergence of bacterial mutants resistant to antibiotics. Treating Animals with uncontrolled amounts of antibiotics will extend beyond their lives and affect humans. This study aims to determine the concentration of the residues of sulfadimidine, sulfaquinoxaline, diaveridine, and vitamin K3 in the tissues of poultry (muscles and liver) after treatment with the combined veterinary formulation. A UPLC-MS-MS method was developed using Poroshell 120 ECC18 and a mobile phase composed of acetonitrile and distilled water, containing 0.1 % formic acid, in the ratio of (85:15 v/v) at a flow rate of 0.6 mL/min. Sample extraction solvent was optimized using response surface methodology (RSM) to be acetonitrile: methanol in the ratio (49.8: 50.2 v/v), and the method was validated according to the FDA bioanalytical method validation protocol over the range (50-1000 µg/Kg) for sulfaquinoxaline and (50-750 µg/Kg) for the other 3 drugs. The greenness of the sample preparation and analytical method was assessed by applying Analytical Eco-scale (AES) and AGREE coupled with AGREEprep. The Competence of the study was evaluated via the EVG framework known as Efficiency, validation, and greenness, to achieve a balance point represented by a radar chart. The method was applied to decide the time required for poultry products to be safe for human use after administration of the studied drugs. It was found that, after the administration of the last dose, minimally 7 days are required till the levels of the drugs drop to the maximum residue limit determined by the FDA/WHO in animal tissues.

Utility of N-Bromosuccinimide-Water Combination as a Green Reagents for a Validated Indirect Spectrophotometric Determination of Some Antihypertensive Drugs: An Application to Their Monitoring in Marketed Tablets and Capsules.

BACKGROUND: Analytical tests were conducted to investigate the use of N-bromosuccinimide (NBS) as an important, safe analytical reagent for the spectrophotometric detection of therapeutically significant dihydropyridine-based calcium antagonists (DHP), namely nifedipine (NIF) and amlodipine (AML), which have been demonstrated to possess antioxidant activity in vivo and to reduce the intracellular production of reactive oxygen species (ROS). Following the reaction of DHP and NBS in acidic media, the excess NBS was evaluated for the first time by its interaction with P-aminophenol (PAP), which produced a violet-colored product that was detected at 556 nm. OBJECTIVE: The analytical method was performed and validated since different variables disturbing the reaction (concentration of reagent, type and concentration of the selected acid, reaction time and the diluting solvents) were carefully studied and optimized. METHODS: The stoichiometry of the applied reaction was determined by Job's method of continuous variation. Monitoring of these drug dosage forms' content uniformity is a first tool or evidence for their efficacy and safety after their administration. RESULTS: Beer's law was obeyed in the concentration range 1.25-11.0 µg/mL for NIF and 1.25-10.0 µg/mL for AML. The calculated limit of detection (LODs) and limit of quantification (LOQs) for NIF and AML were 0.220, 0.155 µg/mL and 0.519, 0.735 µg/mL, respectively. The precision of the applied method was satisfactory; the RSDs did not exceed 2%. Two greenness assessment tools, the Green Analytical Procedure Index (GAPI) and Analytical Greenness Metric for Sample Preparation (AGREEprep) were used for measuring the environmental friendliness of the recommended method. CONCLUSION: The micro-determinations of content uniformity for NIF and AML in their pharmaceutical dosage forms were extremely comparable with those from official and validated procedures. HIGHLIGHTS: A validated indirect spectrophotometric method for accurate quantification of some 1,4-dihydropyridine drugs using NBS with the aid of PAP. Monitoring of NIF and AML dosage forms' content uniformity as a first tool or evidence for their efficacy and safety after their administration. Greenness evaluation tools, GAPI and AGREEprep, for measuring the environmental friendliness of the recommended method.

When is it safe to eat different broiler chicken tissues after administration of doxycycline and tylosin mixture?

Residues of veterinary drugs in poultry meat have serious health effects on humans (e.g., antimicrobial resistance, carcinogenicity, and hypersensitivity), which make the control of veterinary drug residues an important parameter in ensuring consumer protection.  This work was performed to quantitatively determine two co-formulated anti-infective veterinary agents, tylosin tartrate (TYT) and doxycycline hydrochloride (DOX) in different tissues of broiler chickens (liver, muscles, and fat) using high performance liquid chromatography. The chicken was treated with the recommended dose of a binary mixture of the drugs (Tydovet). Moreover, the study aimed to estimate the withdrawal time of both drugs in chicken tissues. The analysis was done by solvent extraction and solid-phase extraction for clean-up of samples from the tissue matrix, followed by liquid chromatographic determination of the cited drugs with UV-detection. Residue decline with time was tracked, and both antibiotics were found to be more persistent in liver tissues than other tissues (muscle and fat). The effect of freezing and cooking was investigated on tissue residue levels. While freezing had little effect on the concentration of both antibiotics; cooking, as anticipated, led to a marked decline. Therefore, it is recommended to pay attention to the proper withdrawal periods before marketing to ensure the hygienic suitability of broilers edibles for safe human consumption. PRACTICAL APPLICATION: This novel study measures tylosin and doxycycline residues simultaneously in different tissues (muscle, fat, and liver) after administration of Tydovet powder to the broiler chicken. Residues in fat persisted for a longer time than in muscle in case of TYT, whereas the reverse was noticed in DOX.

A Thorough HPLC Assay of Quaternary Veterinary Formulation coupled with Environmental Assessment Tool.

A new and accurate reversed phase HPLC method with UV detection has been established for any veterinarian analyst for simultaneous determination of a veterinary quaternary mixture of sulphadimidine sodium (SDS), sulphaquinoxaline sodium (SQS), diaveridine (DVD) and vitamin K3 (VTK3) in their formulation. The stationary phase was SEA C18 column (250 × 4.6 mm i.d., 5 µm particle size) at 25°C with an isocratic mode, using a mobile phase containing a mixture of methanol:acetonitrile:distilled water in the ratio of (20:20:60, by volume). The flow rate was 0.8 mL min-1, and UV detection was performed at 230 nm. The HPLC assay was coupled with Environmental Assessment Tool (EAT), which represents a simple and proficient approach for profiling the greenness of the method. This takes into consideration the environmental, health and safety issues for all solvents that involved in the chromatographic method and calculates a total score that can be used for comparison of the greenness of different methods. The method was found to be linear over (0.5-30) µg/mL for all cited drugs with mean percentage recoveries (99.56 ± 1.141) for VTK3, (99.56 ± 1.056) for DVD, (99.62 ± 1.482) for SDS and (99.52 ± 1.205) for SQS. The results were statistically compared with those of the official and reported methods; using Student's t-test and F-test, showing no significant difference with respect to accuracy. Specificity of the applied method was assessed by analyzing the laboratory-prepared mixtures. The developed method was validated according to ICH guidelines. The proposed methodology can be applied for rapid routine assay of this combination.

Impact Study of Mathematical Manipulation on the Resolution Efficiency of the Spectrophotometric Technique-An Application on Veterinary Binary Mixture with Overlapping Absorption Bands.

BACKGROUND: The impact of mathematical manipulation on the efficiency of smart spectrophotometric approaches was considered for analyzing a veterinary binary mixture of tylosin tartrate (TYT) and doxycycline hydrochloride (DOX). OBJECTIVE: Based on subtraction which can be response subtraction via numerical factor calculation between two wavelengths. METHOD: Absorbance subtraction (AS) and amplitude summation (A-Sum), or subtraction of constant value or spectrum, was used to eliminate the contribution of the interfering component, as is done in spectrum subtraction (SS), extended ratio subtraction (EXRS), ratio subtraction (RS), and derivative subtraction (DS), or multiplication of a constant value by the divisor to get the spectrum of one component, or division by the normalized spectrum to modulate the original absorption spectrum to concentration as in concentration value and also detected in amplitude modulation (AM). The derivative transformation method (DT) is a form of mathematical manipulation that transforms a derivative to its original absorption form. RESULTS: The consumption of these methods will become more significant in quality control departments for the repetitive quantitative analysis of different veterinary products in both research and industry laboratories. Some manipulations may be used for simultaneous analysis of DOX and TYT, such as absorbance subtraction, amplitude modulation, ratio subtraction and derivative subtraction coupled with spectrum subtraction, concentration value, and amplitude summation, while others may be used for DOX only, such as derivative transformation and constant value. CONCLUSIONS: The recovery percentages confirmed that the accuracy and the reproducibility were approved by the following ICH guidelines. HIGHLIGHTS: 1. Partitioning methods: which perfectly divide the drugs response at the iso-point such as amplitude modulation, absorbance subtraction and amplitude summation. 2. Extracting methods: which easily calculate zero-order of the two cited drugs in such as ratio subtraction were coupled with extended ratio subtraction method (RS-EXRS), spectrum subtraction (SS), constant multiplication method (CM) or extract their derivative spectra such as derivative subtraction. 3. Transforming methods: which able to change the derivatized spectrum to its original zero spectra such as derivative transformation. 4. Graphical methods: which directly measure the concentration of the drugs from the chart.

Comprehensive comparative study of eco-friendly Univariate and multivariate methodological approaches on processing multi-component formulation quality.

This study presents comprehensive comparative study of different eco-friendly spectrophotometric approaches without any sample treatment on processing quaternary mixture of sulphadimidine sodium (SDS), sulphaquinoxaline sodium (SQS), diaveridine (DVD) and vitamin K3 (VTK3). The different univariate complementary resolutions according to the response used for the assay of the cited drugs after applying the processing steps were implemented using successive ratio subtraction coupled with constant multiplication (SRS-CM), absorbance subtraction (AS) and amplitude modulation (AM). On the other hand, multivariate spectrophotometric models were developed and validated for simultaneous determination of the cited mixture. Resolution was accomplished by using two multivariate calibration greener models, including principal component regression (PCR) and partial least-squares (PLS). The proposed approaches are considered environmentally friendly since they use only water as reagent, which is cheap and safe for the operator. The calibration graphs are linear over the range of (4.0-13.0) µg/mL for (SDS), (1.0-10.0) µg/mL for (SQS), (1.0-11.0) µg/mL for (DVD) and (1.0-8.0) µg/mL for (VTK3). Specificity of the applied procedures was assessed by analyzing the laboratory-prepared mixtures and their combined dosage form. The outcomes of the developed methods were statistically compared with those of the official and reported methods; using Student's t-test and F-test, showing no significant difference. The proposed methodologies can be used for the routine analysis of the cited drugs in quality control laboratories.

Novel Stability-Indicating Chemometric-Assisted Spectrophotometric Methods for the Determination of Chlordiazepoxide and Clidinium Bromide in the Presence of Clidinium Bromide's Alkali-Induced Degradation Product.

Two simple and accurate chemometric-assisted spectrophotometric models were developed and validated for the simultaneous determination of chlordiazepoxide (CDZ) and clidinium bromide (CDB) in the presence of an alkali-induced degradation product of CDB in their pure and pharmaceutical formulation. Resolution was accomplished by using two multivariate calibration models, including principal component regression (PCR) and partial least-squares (PLS), applied to the UV spectra of the mixtures. Great improvement in the predictive abilities of these multivariate calibrations was observed. A calibration set was constructed and the best model used to predict the concentrations of the studied drugs. CDZ and CDB were analyzed with mean accuracies of 99.84 ± 1.41 and 99.81 ± 0.89% for CDZ and 99.56 ± 1.43 and 99.44 ± 1.41% for CDB using PLS and PCR models, respectively. The proposed models were validated and applied for the analysis of a commercial formulation and laboratory-prepared mixtures. The developed models were statistically compared with those of the official and reported methods with no significant differences observed. The models can be used for the routine analysis of both drugs in QC laboratories.

Simultaneous determination of mebeverine hydrochloride and chlordiazepoxide in their binary mixture using novel univariate spectrophotometric methods via different manipulation pathways.

Smart, sensitive, simple and accurate spectrophotometric methods were developed and validated for the quantitative determination of a binary mixture of mebeverine hydrochloride (MVH) and chlordiazepoxide (CDZ) without prior separation steps via different manipulating pathways. These pathways were applied either on zero order absorption spectra namely, absorbance subtraction (AS) or based on the recovered zero order absorption spectra via a decoding technique namely, derivative transformation (DT) or via ratio spectra namely, ratio subtraction (RS) coupled with extended ratio subtraction (EXRS), spectrum subtraction (SS), constant multiplication (CM) and constant value (CV) methods. The manipulation steps applied on the ratio spectra are namely, ratio difference (RD) and amplitude modulation (AM) methods or applying a derivative to these ratio spectra namely, derivative ratio (DD(1)) or second derivative (D(2)). Finally, the pathway based on the ratio spectra of derivative spectra is namely, derivative subtraction (DS). The specificity of the developed methods was investigated by analyzing the laboratory mixtures and was successfully applied for their combined dosage form. The proposed methods were validated according to ICH guidelines. These methods exhibited linearity in the range of 2-28µg/mL for mebeverine hydrochloride and 1-12µg/mL for chlordiazepoxide. The obtained results were statistically compared with those of the official methods using Student t-test, F-test, and one way ANOVA, showing no significant difference with respect to accuracy and precision.