Multi-walled carbon nanotubes/carbon black/rPLA for high-performance conductive additive manufacturing filament and the simultaneous detection of acetaminophen and phenylephrine.

The combination of multi-walled carbon nanotubes (MWCNT) and carbon black (CB) is presented to produce a high-performance electrically conductive recycled additive manufacturing filament. The filament and subsequent additively manufactured electrodes were characterised by TGA, XPS, Raman, and SEM and showed excellent low-temperature flexibility. The MWCNT/CB filament exhibited an improved electrochemical performance compared to an identical in-house produced bespoke filament using only CB. A heterogeneous electrochemical rate constant, [Formula: see text] of 1.71 (± 0.19) × 10-3 cm s-1 was obtained, showing an almost six times improvement over the commonly used commercial conductive CB/PLA. The filament was successfully tested for the simultaneous determination of acetaminophen and phenylephrine, producing linear ranges of 5-60 and 5-200 µM, sensitivities of 0.05 µA µM-1 and 0.14 µA µM-1, and limits of detection of 0.04 µM and 0.38 µM, respectively. A print-at-home device is presented where a removable lid comprised of rPLA can be placed onto a drinking vessel and the working, counter, and reference components made from our bespoke MWCNT/CB filament. The print-at-home device was successfully used to determine both compounds within real pharmaceutical products, with recoveries between 87 and 120% over a range of three real samples. This work paves the way for fabricating new highly conductive filaments using a combination of carbon materials with different morphologies and physicochemical properties and their application to produce additively manufactured electrodes with greatly improved electrochemical performance.

Sensitive and selective determination of paracetamol in antipyretic children's syrup with a polyglycine modified glassy carbon electrode.

A sensitive and selective electrochemical sensor for the determination of paracetamol (acetaminophen) is proposed based on a polyglycine-coated glassy carbon electrode. The electrochemical behavior of paracetamol was studied by cyclic voltammetry and differential pulse voltammetry. Under optimal experimental conditions, the peak oxidation current of paracetamol increases linearly in the range of 0.5-75 µM. The limit of detection of paracetamol was 0.03 µM and the limit of quantitation was 0.09 µM. In addition, modified glassy carbon with polyglycine as the sensor was successfully used for the determination of paracetamol in antipyretic children's syrup samples, with a recovery rate of over 95.3%, showing its great application potential in drug analysis.

Polyester resin and graphite flakes: turning conductive ink to a voltammetric sensor for paracetamol sensing.

The development of a disposable electrochemical paper-based analytical device (ePAD) is described using a novel formulation of conductive ink that combines graphite powder, polyester resin, and acetone. As a proof of concept, the proposed sensor was utilized for paracetamol (PAR) sensing. The introduced ink was characterized via morphological, structural, and electrochemical analysis, and the results demonstrated appreciable analytical performance. The proposed ePAD provided linear behavior (R2 = 0.99) in the concentration range between 1 and 60 µmol L-1, a limit of detection of 0.2 µmol L-1, and satisfactory reproducibility (RSD ~ 7.7%, n = 5) applying a potential of + 0.81 V vs Ag at the working electrode. The quantification of PAR was demonstrated in different pharmaceutical formulations. The achieved concentrations revealed good agreement with the labeled values, acceptable accuracy (101% and 106%), and no statistical difference from the data obtained by HPLC at the 95% confidence level. The environmental impact of the new device was assessed using AGREE software, which determined a score of 0.85, indicating that it is eco-friendly. During the pharmacokinetic study of PAR, it was found that the drug has a maximum concentration of 23.58 ± 0.01 µmol L-1, a maximum time of 30 min, and a half-life of 2.15 h. These results are comparable to other studies that utilized HPLC. This suggests that the combination of graphite powder and polyester resin can transform conductive ink into an effective ePAD that can potentially be used in various pharmaceutical applications.

Assessment of selected pharmaceuticals in Riyadh wastewater treatment plants, Saudi Arabia: Mass loadings, seasonal variations, removal efficiency and environmental risk.

Despite increasing interest in pharmaceutical emissions worldwide, studies of environmental contamination with pharmaceuticals arising from wastewater discharges in Saudi Arabia are scarce. Therefore, this study examined occurrence, mass loads and removal efficiency for 15 pharmaceuticals and one metabolite (oxypurinol) from different therapeutic classes in three wastewater treatment plants (WWTPs), in Riyadh city in Saudi Arabia. A total of 144 samples were collected from the influents and effluents between March 2018 and July 2019 and analyzed using Solid Phase Extraction followed by triple quadrupole LC-MS/MS. The average concentrations in the influents and effluents were generally higher than their corresponding concentrations found either in previous Saudi Arabian or global studies. The four most dominant compounds in the influent were acetaminophen, ciprofloxacin, caffeine, and diclofenac, with caffeine and acetaminophen having the highest concentrations ranging between 943 and 2282 µg/L. Metformin and ciprofloxacin were the most frequently detected compounds in the effluents at concentrations as high as 33.2 µg/L. Ciprofloxacin had the highest mass load in the effluents of all three WWTPs, ranging between 0.20 and 20.7 mg/day/1000 inhabitants for different WWTPs. The overall average removal efficiency was estimated high (≥80), with no significant different (p > 0.05) between the treatment technology applied. Acetaminophen and caffeine were almost completely eliminated in all three WWTPs. The samples collected in the cold season generally had higher levels of detected compounds than those from the warm seasons, particularly for NSAID and antibiotic compounds. The estimated environmental risk from pharmaceutical compounds in the studied effluents was mostly low, except for antibiotic compounds. Thus, antibiotics should be considered for future monitoring programmes of the aquatic environment in Saudi Arabia.

Wearable Plasmonic Sweat Biosensor for Acetaminophen Drug Monitoring.

Monitoring the acetaminophen dosage is important to prevent the occurrence of adverse reactions such as liver failure and kidney damage. Traditional approaches to monitoring acetaminophen dosage mainly rely on invasive blood collection. Herein, we developed a noninvasive microfluidic-based wearable plasmonic sensor to achieve simultaneous sweat sampling and acetaminophen drug monitoring for vital signs. The fabricated sensor employs an Au nanosphere cone array as the key sensing component, which poses a substrate with surface-enhanced Raman scattering (SERS) activity to noninvasively and sensitively detect the fingerprint of acetaminophen molecules based on its unique SERS spectrum. The developed sensor enabled the sensitive detection and quantification of acetaminophen at concentrations as low as 0.13 µM. We further evaluated the sweat sensor integrated with a Raman spectrometer for monitoring acetaminophen in drug-administered subjects. These results indicated that the sweat sensor could measure acetaminophen levels and reflect drug metabolism. The sweat sensors have revolutionized wearable sensing technology by adopting label-free and sensitive molecular tracking methods for noninvasive and point-of-care drug monitoring and management.

Highly Efficient Electrochemical Sensing of Acetaminophen by Cobalt Oxide-Embedded Nitrogen-Doped Hollow Carbon Spheres.

With respect to sensor application investigations, hollow mesoporous carbon sphere-based materials of the spinel type of cobalt oxide (Co3O4) and heteroatom-doped materials are gaining popularity. In this contribution, dopamine hydrochloride (DA) and cobalt phthalocyanine (CoPc) precursors were employed to construct a highly homogeneous Co3O4-embedded N-doped hollow carbon sphere (Co3O4@NHCS) by a straightforward one-step polymerization procedure. The resulting Co3O4@NHCS materials may effectively tune the surface area, defect sites, and doping amount of N and Co elements by altering the loading amount of CoPc. The relatively high surface area, greater spherical wall thickness, enriched defect sites, and better extent of N and Co sites are all visible in the best 200 mg loaded Co3O4@NHCS-2 material. This leads to significant improvement in pyridine and graphitic N site concentrations, which offers exceptional electrochemical performance. Electrochemical analysis was used to study the electrocatalytic activity of Co3O4@NHCSs towards the sensing of pharmacologically active significant compounds (acetaminophen). Excellent sensor properties include the linear range (0.001-0.2 and 1.0-8.0 mM), sensitivity, limit of detection (0.07 and 0.11 µM), and selectivity in the modified Co3O4@NHCSs/GCE. The authentic sample (acetaminophen tablet) produces a satisfactory result when used practically.

An effective and stability-indicating method development and optimization utilizing the Box-Behnken design for the simultaneous determination of acetaminophen, caffeine, and aspirin in tablet formulation.

Analytical techniques must be sensitive, specific, and accurate to assess the active pharmaceutical ingredients in pharmaceutical dosage forms. The quality-by-design (QbD) application has proven to be a practical method for magnifying HPLC operations. This article discusses the successfully developed QbD-based stability-indicative LC method for evaluating acetaminophen, caffeine, and aspirin (ASP) in tablet dosage form. To achieve the necessary chromatographic separation, Milli-Q water, methanol, and glacial acetic acid were employed in the following ratios: 63:35:2 (v/v/v) for mobile phase A and 18:80:2 (v/v/v) for mobile phase B. The flow rate, column temperature, and detecting wavelength were 1.0 ml/min, 40°C, and 275 nm, respectively, and an InertSustain C18 analytical column (150 × 4.6 mm, 3 µm) was used. Linearity was between 10.0 and 150.0 µg/ml for ASP and acetaminophen and between 2.6 and 39.0 µg/ml for caffeine. The accuracy findings were more than 97%, and the correlation coefficient for all three components was found to be greater than 0.999. The validated HPLC method yielded reliable and accurate results. ASP was shown to be vulnerable to both acid and alkaline hydrolysis in the forced degradation study. The described method is capable of separating the degradants produced during stress testing and is regarded as stability indicating. The proposed method can be used for a wider range of other formulations with an appropriate diluent selection and sample preparation procedure optimization.

Enhanced fluorimetric detection of diphenylpyraline HCl using micelle and cyclodextrin mediated approach: Spectrofluorimetric and micellar liquid chromatographic application for either single or combined formulation with caffeine and paracetamol.

Highly sensitive micellar spectrofluorimetric method (Method I) has been developed and validated for the determination of diphenylpyraline HCl in pharmaceutical tablets and in plasma. Sodium dodecyl sulfate improves the intensity of fluorescence of diphenylpyraline at 286 nm at pH 5 that allow its determination in plasma at nano-level. the mean percent recovery ± S.D was 99.719 ± 0.338 in plasma. In addition, Green cyclodextrin-modified micellar liquid chromatographic method (Method II) has been developed and validated for simultaneous determination of diphenylpyraline, paracetamol and caffeine using cyclodextrin micellar mobile phase consisted of 30 mM Brij*35, 0.5 mM hydroxypropyl ß-cyclodextrin and phosphate buffer pH 4: MeOH (95:5, %v/v) that allows their simultaneous determination with enhanced spectrofluorimetric detection of diphenylpyraline. Method II was effectively applied for the simultaneous determination of diphenylpyraline, paracetamol and caffeine in a ternary laboratory prepared mixture which contained all possible excipients with mean percent recoveries ± S.D of 100.176 ± 1.008, 101.166 ± 0.415 and 100.708 ± 1.836, respectively. Linearity range for Method I was 0.1-1 µg. mL-1 for diphenylpyraline and for Method II was 0.3-50, 25-350, and 0.5-50 for caffeine, paracetamol and diphenylpyraline, respectively. Method I was also applied in spiked human plasma with linearity range 0.2-0.5 µg. mL-1. The methods are verified to have excellent greenness.

The palliative effect of mulberry leaf and olive leaf ethanolic extracts on hepatic CYP2E1 and caspase-3 immunoexpression and oxidative damage induced by paracetamol in male rats.

This study investigated the possible protective role of mulberry leaf (MLE) and olive leaf (OLE) ethanolic extracts against paracetamol (PTL)-induced liver injury in rats compared to silymarin as a reference drug. Initially, MLE and OLE were characterized using gas chromatography-mass spectrometry (GC/MS). Then, forty male Sprague Dawley rats were divided into five groups: the negative control group orally received distilled water for 35 days, the PTL-treated group (PTG) received 500 mg PTL/kg b. wt. for 7 days, the MLE-treated group (MLTG) received 400 mg MLE/kg b. wt., the OLE-treated group (OLTG) received 400 mg OLE/kg b. wt., and the silymarin-treated group (STG) received 100 mg silymarin/kg b. wt. The last three groups received the treatment for 28 days, then PTL for 7 days. The GC-MS characterization revealed that MLE comprised 19 constituents dominated by ethyl linoleate, phytol, hexadecanoic acid, ethyl ester, and squalene. Moreover, OLE comprised 30 components, and the major components were 11-eicosenoic acid, oleic acid, phytol, and à-tetralone. MLE and OLE significantly corrected the PTL-induced normocytic normochromic anemia, leukocytosis, hypercholesterolemia, and hypoproteinemia. Moreover, the MLE and OLE pretreatment considerably suppressed the PTL-induced increment in serum levels of hepatic enzymes, including alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase. Furthermore, the PTL-induced depletion in antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase, and the rise in hepatic malondialdehyde content were significantly reversed by the MLE and OLE pretreatment. Besides, MLE and OLE pretreatment significantly protected the hepatic tissue against PTL-induced DNA damage, pathological perturbations, and increased caspase 3 and CYP2E1 immunoexpression. Of note, OLTG showed better enhancement of most indices rather than MLTG. Conclusively, these findings imply that OLE, with its antioxidant and antiapoptotic capabilities, is superior to MLE in protecting against PTL-induced liver injury.

Sensitive electrochemical assay of acetaminophen based on 3D-hierarchical mesoporous carbon nanosheets.

Acetaminophen plays a key role in first-line Covid-19 cure as a supportive therapy of fever and pain. However, overdose of acetaminophen may give rise to severe adverse events such as acute liver failure in individual. In this work, 3D-hierarchical mesoporous carbon nanosheet (hMCNS) microspheres with superior properties were fabricated using simple and quick strategy and applied for sensitive quantification of acetaminophen in pharmaceutical formulation and rat plasmas after administration. The hMCNS microspheres are prepared via chemical etching of zinc oxide (ZnO) nanoparticles from a zinc-gallic acid precursor composite (Zn-GA) synthesized by high-temperature anaerobic pyrolysis. The obtained hMCNS could enhance analytes accessibility and accelerate proton transfer in the interface, hence increasing the electrochemical performance. Under optimized experimental conditions, the proposed electrochemical sensor achieves a detection limit of 3.5 nM for acetaminophen. The prepared electrochemical sensor has been successfully applied for quantification of acetaminophen in pharmaceutical formulations and the rat plasma samples before and after administration. Meanwhile, this sensor is compared with high-performance liquid chromatography (HPLC) as a reference technology, showing an excellent accuracy. Such an electrochemical sensor has great potential and economic benefits for applications in the fields of pharmaceutical assay and therapeutic drug monitoring (TDM).

Synthesis and standardization of an impurity of acetaminophen, development and validation of liquid chromatographic method.

One of the impurities of acetaminophen, N,N'-(oxydi-4,1-phenylene)diacetamide (ODAA), which is not specified in the organic impurities analysis method of acetaminophen by high performance liquid chromatography (HPLC) in American Pharmacopoeia Version 42 (USP 42), was synthesized, characterized and standardized. A new and optimized liquid chromatographic method for the determination of organic impurities of acetaminophen was developed using an ultra-high performance liquid chromatographic (UHPLC) system, which can separate this impurity. This new liquid chromatographic method has been optimized and validated for the simultaneous determination of acetaminophen related compound B, acetaminophen related compound C, acetaminophen related compound D, acetaminophen related compound J and ODAA, the organic impurities in acetaminophen drug substance. Acetaminophen was also subjected to stress-testing under acidic hydrolysis, alkaline hydrolysis, oxidative degradation, thermal degradation and photolytic degradation for 15 days. The impurity molecule, ODAA was synthesized using 4,4'-oxydianiline and acetic anhydride. The chemical structure of the synthesized ODAA molecule was confirmed by characterization studies. The potency of ODAA was found to be 99.64% as a result of the relevant analyses. The chromatographic separation was achieved on a C8 (150 mm × 2.1 mm; 2-µm particle size) reversed-phase column using a gradient elution, being solvent A: methanol-water-glacial acetic acid (50:950:1, v/v/v) and solvent B: methanol-water-glacial acetic acid (500:500:1, v/v/v) flowing at a rate of 0.2 mL/min. The limits of quantitation (S/N 10:1) were 1.248 µg/mL for acetaminophen, 0.373 µg/mL for acetaminophen related compound B, 1.217 µg/mL for acetaminophen related compound C, 0.369 µg/mL for acetaminophen related compound D, 0.125 µg/mL for acetaminophen related compound J and 0.373 µg/mL for ODAA. The individual mean recoveries of each impurity molecule spiked into acetaminophen samples at different concentration levels ranged from 93% to 104%. The method developed for UHPLC instrument was successfully applied to the analyses of different lots of acetaminophen. Thus, the proposed method can be used for determination of this impurity in the presence of other specified impurities of acetaminophen.

A miniaturized electrochemical device based on the nitrogen, carbon-codoped bimetal for real-time monitoring of acetaminophen and dopamine in urine.

In-situ real-time detection of drug metabolites and biomolecules in hospitalized patients' urine helps the doctors to monitor their physiological indicators and regulate the use of drug doses. In this work, nitrogen-doped carbon-supported bimetal was prepared into the screen-printed electrodes (SPEs) and applied for real-time monitoring of acetaminophen (AC) and dopamine (DA) in urine. Via one-step pyrolysis of the core-shell cubic precursor (Cu3[Co(CN)6]2@Co3[Co(CN)6]2, CuCo@CoCo), the nitrogen-doped carbon-supported bimetal (CuCo-NC) was formed. The bimetal composites presented twice higher catalytic activity than the counterparts with single metal. In addition, the nanocomposites exhibited strong conductivity after pyrolysis, promoting electron transport efficiency as indicated by impedance measurements. Accordingly, the CuCo-NC based sensor offered excellent sensitivity with the detection limits down to 50 nM and 30 nM at the detection range of 0.1-400 µM and 0.2-200 µM for detection of AC and DA, respectively. Finally, in combination with a miniaturized electrochemical device, the sensor was applied for in-situ real-time monitoring of AC and DA in the urinary bag for up to 12h. As compared with other techniques such as high-performance liquid chromatography, UV-spectrophotometry and fluorescence spectrometer, the biosensor demonstrated the advantages of real-time monitoring, easy operation and excellent portability. However, the multi-component detection and self-calibration function need to be further developed. This method paves a way for the continuous monitoring of drug metabolites and biomolecules of hospitalized patients.

Ultra-performance chromatography-electrospray tandem mass spectrometry analysis of bile acid profiles in the enterohepatic circulation following geniposide and acetaminophen-induced liver injury.

Bile acids (BAs) play an important role in pre-diagnosing drug-induced liver injury (DILI). However, in clinical practice, different types of liver injury are characterized by different pathogeneses and pathological manifestations. Therefore, whether BAs can be used as biomarkers across different DILIs remains unclear. In this study, an ultra-performance chromatography-mass spectrometry (MS)/MS-based technique was developed for the simultaneous quantitative analysis of 31 BAs in the serum, liver, feces, urine, and intestinal contents of rats treated with acetaminophen (APAP) and geniposide to induce liver injury. The total extraction recovery for representative analytes ranged between 80.60% and 99.23% in the serum, urine, liver, feces, and intestinal contents. The correlation coefficients for all standard curves of the different matrices were at least 0.99. Validation of the BA analytical method including selectivity, residue, lower limit of quantification, accuracy, precision, matrix effect, and stability conformed with the biospecimen quality control standards of the Chinese Pharmacopoeia (version 2020). Serum biochemical and pathohistological analyses revealed APAP- and geniposide-induced hepatocellular and cholestatic DILI, respectively, with different effects on BA profiles in the enterohepatic circulation. Metabolomics further revealed that the trends in BA changes in the serum, feces, urine, and intestinal tissues were consistent between the geniposide- and APAP-treated groups. However, in the liver, the total BAs (TBA) concentration increased by 1.70 fold in the geniposide group but decreased by 43% in the APAP group compared with the control group. Multivariate analysis revealed differentially expressed BAs, including TCA, CA, and GCA, which are potential biomarkers for DILI, in the serum, liver, and urine following treatment with geniposide. Interestingly, the differentially expressed BAs in the APAP group were similar to those in the control group. Additionally, the magnitude of changes in the TBA in the urine (3.3 fold and 15.5 fold in the APAP and geniposide groups, respectively) was higher than that in the blood (290 fold and 640 fold in the APAP and geniposide groups, respectively). However, given the BA profiles after geniposide- and APAP-induced liver injury, BAs were found to be more suitable as biomarkers for diagnosing cholestatic liver injury. Overall, the BA assay developed in this study is rapid, simple, accurate, validated, sensitive, and suitable for analyzing the levels and distribution of BAs in various parts of the enterohepatic circulation.

A bibliometric analysis of graphene in acetaminophen detection: Current status, development, and future directions.

Acetaminophen is a widely used analgesic throughout the world. Detection of acetaminophen has particular value in pharmacy and clinics. Electrochemical sensors assembled with advanced materials are an effective method for the rapid detection of acetaminophen. Graphene-based carbon nanomaterials have been extensively investigated for potential analytical applications in the last decade. In this article, we selected papers containing both graphene and acetaminophen. Bibliometrics was used to analyze the relationships and trends among these papers. The results show that the topic has grown at a high rate since 2009. Among them, the detection of acetaminophen by an electrochemical sensor based on graphene is the most important direction. Graphene has moved from being a primary sensing material to a substrate for immobilization of other active ingredients. In addition, the degradation of acetaminophen using graphene-modified electrodes is also an important direction. We analyzed the research history and current status of this topic through bibliometrics. Authors, institutions, countries, and key literature were discussed. We also proposed perspectives for this topic.

Recent advances in electrochemical sensor developments for detecting emerging pollutant in water environment.

In the latest times, considerable studies have been performed closer to detecting emerging pollutant such as paracetamol in wastewater. Electrochemical sensor developments have recently started to determine in fewer concentrations effectively. The detection of paracetamol using standard protocols corresponding to electroanalytical techniques has a greater impact noticed in directing the detecting process toward biosensors. Non-enzymatic sensors are the peak of all electro analysis approaches. Functionalized materials, such as metal oxide nanoparticles, conducting polymers, and carbon-based materials for electrode surface functionalization have been used to create a fortification for distributing passive enzyme-free biosensors. Synergic effects are possible by enhancing loading capacity and mass transfer of reactants for attaining high analytical sensitivity using a variety of nanomaterials with large surface areas. The main focus of this study is to address the prevailing issues in the identification of paracetamol with the tasks in the non-enzymatic sensors field, followed by the useful methods of electro analysis studies.

Validation of three analytical methods for quantification of acetaminophen by UV spectrophotometry

Introduction: Acetaminophen is a non-steroidal analgesic and antipyretic, whose mechanism is based on the inhibition of the cyclooxygenase enzyme responsible for the appearance of pain and inflammation. In Mexico, it is one of the drugs widely used for its effectiveness, which is why the objective of this study was to implement a method of chemical validation by ultraviolet spectrophotometry that allows the quantification of this active principle. Method: We worked with 4 dissolution media (HCl: 0.1N MeOH, 0.1M HCl, Methanol: Water in a ratio of 15:85 p / v and 0.2M phosphate buffer). All four media underwent analytical validation, measuring linear regression significance, precision, sample stability, and sensitivity. Results:The 0.1M HCl, MeOH: H2O (15:85 v / v) and Phosphate Buffer media comply with the significance of the intercept, linearity of the method, as well as the parameters of precision, stability, and with the limits of detection (DL) and the limit of quantification (QL). Discarding the HCl: 0.1N MeOH medium for not meeting the linearity parameters. Conclusions: Of the fourth means evaluated, three of them (0.1M HCl, Methanol: water, and phosphate buffer) can be used as alternatives in the quantification of this drug (AU)

Introducción: El acetaminofén es un analgésico y antipirético no esteroideo, cuyo mecanismo se basa en la inhibición de la enzima ciclooxigenasa responsable de la aparición de dolor e inflamación. En México es uno de los fármacos ampliamente usados por su efectividad, es por ello, el objetivo de este estudio fue implementar un método de validación química por espectrofotometría ultravioleta que permita la cuantificación de este principio activo. Método: Se trabajó con 4 medios de disolución (HCl:MetOH 0,1N, HCl 0,1M, Metanol: Agua en proporción 15:85 p/v y solución amortiguadora de fosfatos 0,2M). Los cuatro medios se sometieron a una validación analítica, midiendo Significancia de la regresión lineal, precisión, estabilidad de la muestra y sensibilidad.Resultados:Los medios HCl 0,1M, MetOH:H2O (15:85 v/v) y Buffer de fosfatos cumplen con la significancia del intercepto, linealidad del método, así como los parámetros de precisión, estabilidad y con los límites de detección (DL) y el límite de cuantificación (QL). Descartando el medio de HCl: MetOH 0,1N por no cumplir con los parámetros de linealidad. Conclusiones: De los cuatro medios evaluados tres de ellos (HCl 0,1M, Metanol: agua y amortiguador de fosfatos) se pueden usar como alternativas en la cuantificación de este fármaco (AU)

Analytical Performance of Clay Paste Electrode and Graphene Paste Electrode-Comparative Study.

The analytical performance of the clay paste electrode and graphene paste electrode was compared using square wave voltammetry (SWV) and cyclic voltammetry (CV). The comparison was made on the basis of a paracetamol (PA) determination on both working electrodes. The influence of pH and SWV parameters was investigated. The linear concentration ranges were found to be 6.0 × 10-7-3.0 × 10-5 and 2.0 × 10-6-8.0 × 10-5 mol L-1 for clay paste electrode (ClPE) and graphene paste electrode (GrPE), respectively. The detection and quantification limits were calculated as 1.4 × 10-7 and 4.7 ×10-7 mol L-1 for ClPE and 3.7 × 10-7 and 1.2 × 10-6 mol L-1 for GrPE, respectively. Developed methods were successfully applied to pharmaceutical formulations analyses. Scanning electron microscopy and energy-dispersive X-ray spectroscopy were used to characterize ClPE and GrPE surfaces. Clay composition was examined with wavelength dispersive X-ray (WDXRF).

Simultaneous Quantitation of Paracetamol and Lornoxicam in the Presence of Five Related Substances and Toxic Impurities by a Selective HPLC-DAD Method.

OBJECTIVE: This research describes the simultaneous quantitation of paracetamol (PRM) and lornoxicam (LRX) with five of their related substances and toxic impurities, including, 4-nitrophenol (NTP), 4-aminophenol (AMP), 4-chloroacetanilide (CAC), N-phenylacetamide (NPA), and 2-aminopyridine (APD) using a specific HPLC-diode array detector (DAD) method. METHODS: The chromatographic separation involves the use of a XTerra C18 column as the stationary phase and a mobile phase consisting of acetonitrile and 0.025 M phosphate buffer (pH 6). The separation was performed using gradient elution mode at 1.0 mL/min flow rate and detection at 260 nm for the determination of PRM and LRX. For detecting PRM and LRX in the presence of their toxic impurities, 270 nm was used. Validation of the suggested HPLC method was accomplished with regard to linearity, ranges, detection and quantitation limits, robustness, accuracy, precision, and specificity. RESULTS: Excellent resolution of the mixture components was accomplished at retention times 4.2, 4.8, 7.4, 11.1, 13.5, 14.7, and 15.3 min for APD, AMP, PRM, NPA, LRX, NTP, and CAC, respectively. Linearity was established for PRM and LRX within concentration ranges of 10-100 and 10-60 µg/mL, respectively. The correlation coefficients obtained were >0.9997. The suggested method was confirmed to be a specific stability-indicating through the selective separation of PRM and LRX from their related substances, degradants, and impurities. CONCLUSION: The proposed method was successfully utilized for the sensitive and selective determination of PRM and LRX in their pharmaceutical formulation. HIGHLIGHTS: To the best of our knowledge, this is the first impurity profiling assay method for this combination in the presence of five of their toxic related substances and impurities. Taking into consideration that at least two of the studied impurities (AMP and APD) are actually reported degradation products for the main drugs, the suggested method can be considered stability-indicating as well.

Stability-Indicating New RP-UPLC Method for Simultaneous Determination of a Quaternary Mixture of Paracetamol, Pseudoephedrine, Chlorpheniramine, and Sodium Benzoate in (Cold-Flu) Syrup Dosage Form.

BACKGROUND: A combination of paracetamol, pseudoephedrine, chlorpheniramine, and sodium benzoate in (Cold-Flu) 1,2,3 Syrup dosage form is specified for the treatment of common cold and flu symptoms. OBJECTIVE: The functional role of this study is to develop a novel, reliable, and selective stability-indicating reversed-phase ultra-performance liquid chromatography (RP-UPLC) method for simultaneous identification of a quaternary mixture of paracetamol, pseudoephedrine, chlorpheniramine, and sodium benzoate in (Cold-Flu) 1,2,3 Syrup dosage form. METHOD: The specific method is accomplished using an Acquity UPLC HSS T3 C18 column (2.1 mm × 100 mm), 1.8 µm particle size with pore size 100 Å, utilizing a mixture of purified water-methanol-trifluoroacetic acid (72.5:27.5:1.5, v/v) as the mobile phase at a flow rate of 0.3 mL/min. The column void volume is 1.15 min. UPLC detection is adjusted at 205 nm using a photodiode array detector. RESULTS: Calibration curves are obtained in the linearity ranges: 25-500 µg/mL for paracetamol, 10-50 µg/mL for pseudoephedrine, 0.5-5 µg/mL for chlorpheniramine, and 3-30 µg/mL for sodium benzoate with a correlation coefficient > 0.9992. The mean recovery of the developed method is tested and shows good recovery results between 99-101%; selectivity and forced degradation studies are investigated as per the International Council for Harmonisation Guidelines and no interference is detected due to degradation peaks. CONCLUSION: The proposed stability-indicating UPLC method for simultaneous determination of the three drugs, paracetamol, pseudoephedrine, and chlorpheniramine, with a preservative sodium benzoate in (Cold-Flu) 1,2,3 Syrup dosage form is successfully accomplished, developed, and validated, and can be easily used in the analysis of drugs in pure or dosage form. HIGHLIGHTS: The novelty of the current research work lies in the development of the UPLC method for simultaneous determination of a quaternary mixture of paracetamol, pseudoephedrine, chlorpheniramine, and sodium benzoate in (Cold-Flu) 1,2,3 Syrup dosage form.

A novel strategy on the spectrochromatographic analysis of a quaternary mixture by parallel factor analysis model.

Poor chromatographic resolution is one of the main challenges in chromatographic analysis. Partially separated chromatographic peaks frequently occur, due to the nature of analytes and the demand for fast analysis using high flow rates and shorter columns. Modeling of chromatographic three-way data using suitable chemometric tools enables determining co-eluted peaks without using additional experimental efforts. In this paper, parallel factor analysis (PARAFAC) was applied to chromatographic data for the quantitative resolution of a quaternary mixture at the co-elution condition of acetaminophen, aspirin, ascorbic acid, and guaifenesin in a spectrochromatogram. The spectrochromatograms of the calibration set, validation set, and real samples were arranged as a three-way array. In the next step, the PARAFAC model was implemented to decompose the spectrochromatographic array into trilinear components, corresponding to spectral, chromatographic, and relative concentration profiles of the analytes. The chromatographic and spectral modes were used for the qualitative analysis of components, whereas the analytes in commercial tablets were quantified from their individual profiles in their concentration mode. This study indicated that the application of the PARAFAC model provided a novel strategy for determining overlapping peaks in a chromatogram to perform the analysis of multicomponent mixtures with reduced runtime and without additional efforts.