Continuous stationary phase gradient preparation on planar chromatographic media using vapor phase deposition of silane.

A new, versatile, and straightforward vapor phase deposition (VPD) approach was used to prepare continuous stationary phase gradients (cSPGs) on silica thin-layer chromatography (TLC) plates using phenyldimethylchlorosilane (PDCS) as a precursor. A mixture of paraffin oil and PDCS was placed at the bottom of an open-ended rectangular chamber, allowing the reactive silanes to evaporate and freely diffuse under a controlled atmosphere. As the volatile silane diffused across the length of the TLC plate, it reacted with the surface silanol groups thus functionalizing the surface in a gradient fashion. Characterization of the gradient TLC plates was done through UV visualization and diffuse reflectance spectroscopy (DRS). Visualizing the fluorescent gradient plates under UV radiation shows the clear presence of a gradient with the side closest to the vapor source undergoing the most modification. More quantitative characterization of the shape of the gradient was provided by DRS. The DRS showed that the degree of modification and shape of the gradient was dependent on the concentration of silane, VPD time, and relative humidity. To evaluate the chromatographic performance, a mixture of three aromatic compounds (acetaminophen (A), aspirin (As), and 3-hydroxy-2-naphthoic acid (3H)) was spotted on the high (GHP) and low phenyl (GLP) ends of the gradient TLC plates and the results compared to the separations carried out on unmodified and uniformly modified plates. The GHP TLC plates showed retention factors (Rf) of 0.060 ± 0.006, 0.391 ± 0.006, and 0.544 ± 0.006, whereas the unmodified plate displayed Rf values of 0.059 ± 0.006, 0.092 ± 0.003, and 0.037 ± 0.002 for the analytes A, As, and 3H, respectively. From the Rf values, it was observed that each modified plate exhibited different selectivity for the analytes. The GHP TLC plates exhibited better separation performance, and improved resolution compared to the GLP, unmodified, and uniformly modified plates. Overall, VPD is a new, cost-effective method for creating a gradient on the stationary phase which has the potential to advance chromatographic separation capabilities.

Synchronous analysis of acetaminophen, codeine, and caffeine in human fluids employing graphite screen-printed electrodes.

A facile electrochemical approach is proposed for the synchronous determination of acetaminophen (ACP), codeine (COD) and caffeine (CAF) utilizing unmodified screen-printed electrodes (SPEs). The determination of ACP, COD and CAF has been explored across different supporting electrolytes including sulfuric acid (H2SO4), hydrochloric acid (HCl), phosphoric acid (H3PO4) and Briton Robinson (B.R) buffer solutions. It was found that a 0.05 mol L-1 sulfuric acid solution is an optimal supporting electrolyte utilized for voltammetric analysis of ACP, COD, and CAF with improved sensitivity, stability, and reproducibility. The electro-analytical sensing of ACP, COD and CAF was investigated using SPEs within linear concentration ranges of 3.0-35.0 µmol L-1, 10-160 µmol L-1 and 10-160 µmol L-1 and revealed competitively low limits of detection (3S/N) of 0.9, 4.8 and 6.3 µmol L-1 for ACP, COD and CAF, respectively. The results indicated the possibility of such a simple and quick electroanalytical protocol for online monitoring of pharmaceutical formulations comprising ACP, COD, and CAF drugs in human fluids with satisfactory recovery.

Optimization, kinetics, and pathways of pharmaceutical pollutant degradation using solar Fenton technique.

Solar Fenton is an important and extensively used advanced oxidation process (AOP) to degrade pharmaceutical pollutants. The objective of this study was to evaluate the performance of simultaneous degradation of the mixed pollutants (amoxicillin, acetaminophen, and ciprofloxacin) for an aqueous solution using the solar Fenton process. Operating parameters such as pH, iron doses, H2O2 doses, pollutant concentrations, and time were studied. From the experimental results, the ideal conditions were obtained for the removal of mixed pollutants such as pH 3, Fe2+ 0.04 mM, H2O2 4 mM, the concentration of the mixed pollutants 5 mg/L, solar radiation 400 W/m2, and time 10 min, respectively. The pseudo-first-order kinetics were utilized to investigate the degradation efficacy of the mixed pollutants. The result of the study indicates that the degradation efficiency was > 99% for the mixed pollutants. A maximum of 63% mineralization was observed, and hydroxyl radical scavenger effects were studied. The best optimal conditions were applied to assess the spiked wastewater (municipal wastewater (MWW) and hospital wastewater (HWW)). The highest elimination rates for AMX, ACET, and CIP were observed as 65%, 89%, and 85% for MWW and 76%, 92%, and 80% for HWW, respectively. The degraded by-products were detected by LC-ESI-MS in the water matrix (aqueous solution and spiked wastewater), and ECOSAR analysis was performed for the transformed products. The study concluded that the solar Fenton technique is promising and effective for the removal of mixed pollutants from the water matrix.

Proving the automatic benchtop electrochemical station for the development of dopamine and paracetamol sensors.

The introduced work represents an implementation of the automatic benchtop electrochemical station (BES) as an effective tool for the possibilities of high-throughput preparation of modified sensor/biosensors, speeding up the development of the analytical method, and automation of the analytical procedure for the determination of paracetamol (PAR) and dopamine (DOP) as target analytes. Within the preparation of gold nanoparticles modified screen-printed carbon electrode (AuNPs-SPCE) by electrodeposition, the deposition potential EDEP, the deposition time tDEP, and the concentration of HAuCl4 were optimized and their influence was monitored on 1 mM [Ru(NH3)6]3+/2+ redox probe and 50 µM DOP. The morphology of the AuNPs-SPCE prepared at various modification conditions was observed by SEM. The analytical performance of the AuNPs-SPCE prepared at different modification conditions was evaluated by a construction of the calibration curves of DOP and PAR. SPCE and AuNPs-SPCE at modification condition providing the best sensitivity to PAR and DOP, were successfully used to determine PAR and DOP in tap water by "spike-recovery" approach. The BES yields better reproducibility of the preparation of AuNPs-SPCE (RSD = 3.0%) in comparison with the case when AuNPs-SPCE was prepared manually by highly skilled laboratory operator (RSD = 7.0%).

Development of a novel UPLC approach to co-prediction of four active compounds in a multi-component pharmaceutical preparation.

In this work, a new ultra-performance liquid chromatography method based on photodiode array detection (UPLC-PDA) was first developed for the quantitative analysis of the quaternary mixture of ascorbic acid (AA), paracetamol (PAR), caffeine (CAF) and chlorpheniramine maleate (CPA) in a commercial dosage form. The developed UPLC-PDA method offered a new possibility for the co-determination of four active ingredients in a drug combination with short run time and simple sample preparation. The successful chromatographic separation of the four drugs was performed using a Waters Acquity UPLC BEH C18 column (1.7 µm 2.1 × 100 mm) (Mildford, USA) and a mobile phase consisting of water (12 %), acetonitrile (13 %) and 0.1 M H3PO4 (75 %) at a flow rate of 0.25 mL/min. The validation of the proposed UPLC-PDA approach was verified by analyzing synthetic mixtures, inter- and intra-day experiments, and commercial powder samples and provided satisfactory results.

A Novel Low-Frequency Electromagnetic Active Inertial Sensor for Drug Detection.

The purpose of this paper is to demonstrate a new discovery regarding the interaction between materials and very low radio frequencies. Specifically, we observed a feedback response on an inertia active sensor when specific frequencies (around 2-4 kHz) are used to irradiate targeted pharmaceutical samples like aspirin or paracetamol drugs. The characteristics of this phenomenon, such as excitation and relaxation time, the relation between deceleration and a material's quantity, and signal amplitude, are presented and analyzed. Although the underlying physics of this phenomenon is not yet known, we have shown that it has potential applications in remote identification of compounds, detection, and location sensing, as well as identifying substances that exist in plants without the need for any processing. This method is fast, accurate, low-cost, non-destructive, and non-invasive, making it a valuable area for further research that could yield spectacular results in the future.

A miniaturized additive-manufactured carbon black/PLA electrochemical sensor for pharmaceuticals detection.

Additive manufacturing is a technique that allows the construction of prototypes and has evolved a lot in the last 20 years, innovating industrial fabrication processes in several areas. In chemistry, additive manufacturing has been used in several functionalities, such as microfluidic analytical devices, energy storage devices, and electrochemical sensors. Theophylline and paracetamol are important pharmaceutical drugs where overdosing can cause adverse effects, such as tachycardia, seizures, and even renal failure. Therefore, this paper aims at the development of miniaturized electrochemical sensors using 3D printing and polylactic acid-based conductive carbon black commercial filament for theophylline and paracetamol detection. Electrochemical characterizations of the proposed sensor were performed to prove the functionality of the device. Morphological characterizations were carried out, in which chemical treatment could change the surface structure, causing the improvement of the analytical signal. Thus, the detection of theophylline at a linear range of 5.00-150 µmol L-1 with a limit of detection of 1.2 µmol L-1 was attained, and the detection of paracetamol at a linear range of 1.00-200 µmol L-1 with a limit of detection of 0.370 µmol L-1 was obtained, demonstrating the proposed sensor effectively detected pharmaceutical drugs.

Detection of acetaminophen and P-aminophenol simultaneously by an electrochemical sensor based on Fe-NC derivatives attached with Ti3C2 QDs.

In this paper, Ti3C2 QDs and Fe-ZIF-8 were synthesized by a straightforward hydrothermal method. Fe-ZIF-8 was pyrolyzed at high temperatures to obtain Fe-nanoclusters (Fe-NC). Then Fe-NC is mixed with Ti3C2 QDs to form a new composite material (Ti3C2 QDs/Fe-NC), and its microstructure and composition were analyzed by technology. The proposed material can detect acetaminophen (PA) and P-aminophenol (4-AP) simultaneously with excellent detection performance. With the best conditions, the linear ranges and detection limits were 0.50-210.00 µM, 0.03 µM (S/N = 3) and 0.50-150.00 µM, 0.06 µM (S/N = 3) for PA and 4-AP, respectively. The sensor has lower detection limits and wider linear ranges, and can successfully detect 4-AP and PA in river water and acetaminophen tablets at the same time, showing potential practical application prospects. Especially, this study reports the modification of MOF derivatives with Ti3C2 QDs for the first time, which expands the application scope of Quantum Dots and MOF derivatives.

Anthraquinone/activated carbon electrochemical sensor and its application in acetaminophen analysis.

Acetaminophen (AC) can inhibit the synthesis of prostaglandins in the body, and has antipyretic and analgesic effects. In this paper, a two-step microwave impregnation method was used to prepare anthraquinone (AQ)-doped carbon composite, which were applied to the surface modification of glassy carbon electrodes (GCE) for the determination of acetaminophen (AC) using differential pulse voltammetry (DPV). The composites were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman and Fourier infrared spectroscopy (FT-IR). The results showed that anthraquinone was successfully modified on the surface of activated carbon. The peak current of AC increased with its concentration in the range of 0.1 µM to 700 µM (R2 = 0.998) and a detection limit of 0.05 µM was obtained with 20%AQ doped carbon electrochemical sensor (20%AQ-C/GCE). Electrochemical Impedance Spectroscopy (EIS) test results indicated that the charge transfer resistance (Rct) of 20%AQ-C/GCE is only the one-fourth of that of bare GCE. The proposed 20%AQ-C/GCE sensor has good stability, reproducibility and selectivity for the detection of AC. The sensor is also suitable for the detection of real samples, indicating its good practicality.

Circular economical approach of extracting nanocarbons from waste pea peel for sensing of p-nitrophenol and its conversion into paracetamol.

An important paradigm shift towards the circular economy is to prioritize waste prevention, reuse, recycling, and recovery before disposal is necessary. In this context, a sustainable protocol of converting waste pea peel (wPP) into low-cost carbon nanomaterials for sensing and conversion of p-nitrophenol (p-NP) into value-added paracetamol is being reported. Two fractions of the carbonaceous nanomaterials were obtained after the hydrothermal treatment (HT) of wPP, firstly an aqueous portion containing water-soluble carbon dots (wPP-CDs) and a solid residue, which was converted into carbonized biochar (wPP-BC). Blue-colored fluorescent wPP-CDs displayed excitation-dependent and pH-independent properties with a quantum yield (QY) of 8.82 %, which were exploited for the fluorescence sensing of p-NP with 4.20 µM limit of detection. Pyrolyzed biochar acting as an efficient catalyst effectively reduces p-NP to p-aminophenol (p-AP) in just 16 min with a 0.237 min-1 rate of conversion. Furthermore, the produced p-AP was converted into paracetamol, an analgesic and antipyretic drug, to achieve zero waste theory. Thus, this study provides the execution of sustainable approaches based on the integral valorization of biowaste that can be further recycled and reused, offering an effective way to attain a profitable circular economy.

Highly Sensitive Wearable Sensor Based on (001)-Orientated TiO2 for Real-Time Electrochemical Detection of Dopamine, Tyrosine, and Paracetamol.

The concentration of dopamine (DA) and tyrosine (Tyr) reflects the condition of patients with Parkinson's disease, whereas moderate paracetamol (PA) can help relieve their pain. Therefore, real-time measurements of these bioanalytes have important clinical implications for patients with Parkinson's disease. However, previous sensors suffer from either limited sensitivity or complex fabrication and integration processes. This work introduces a simple and cost-effective method to prepare high-quality, flexible titanium dioxide (TiO2) thin films with highly reactive (001)-facets. The as-fabricated TiO2 film supported by a carbon cloth electrode (i.e., TiO2-CC) allows excellent electrochemical specificity and sensitivity to DA (1.390 µA µM-1 cm-2), Tyr (0.126 µA µM-1 cm-2), and PA (0.0841 µA µM-1 cm-2). More importantly, accurate DA concentration in varied pH conditions can be obtained by decoupling them within a single differential pulse voltammetry measurement without additional sensing units. The TiO2-CC electrochemical sensor can be integrated into a smart diaper to detect the trace amount of DA or an integrated skin-interfaced patch with microfluidic sampling and wireless transmission units for real-time detection of the sweat Try and PA concentration. The wearable sensor based on TiO2-CC prepared by facile manufacturing methods holds great potential in the daily health monitoring and care of patients with neurological disorders.

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.

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.

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.