Pharmaceutical Paracetamol Research Articles

Targeted modification of the carbon paste electrode by natural zeolite and graphene oxide for the enhanced analysis of paracetamol

In this work, the targeted modification of carbon paste (CP) by admixing of conductive graphene oxide (GO) and mesoporous natural zeolite with the introduced Ni2+ cations (NiZ), providing electrocatalytic properties, is presented. The performed univariate optimization indicated that 5 % (w/w) of NiZ and GO in the CP is sufficient to ensure a threefold increase in peak current and lower the overpotential of paracetamol (PAR) oxidation, while retaining a low background current and high signal-to-noise ratio. The fabricated CPE/NiZ/GO sensor ensured a linear response in the PAR concentration range from 0.004 to 0.12 mg L−1, advantageously low limit of detection equal to 0.0012 mg L−1 (0.0078 µM), and high stability of recorded signals (RSD = 3 %). Moreover, the proposed analytical method is characterized by good selectivity and robustness to the presence of interference. The usefulness of the CPE/NiZ/GO was verified by the determination of PAR in pharmaceuticals, human urine and serum, delivering acceptable results.

Couple batch-injection analysis and microfluidic paper-based analytical device: A simple and disposable alternative to conventional BIA apparatus.

Under controlled dispersion conditions, sample injection towards a detector opened essential fields for the Analytical Chemistry fast development methods. Flow injection analysis (FIA) and batch injection analysis (BIA) systems are crucial for injecting the sample in these analytical methods. The BIA system eliminated the flow manifold, with samples injected directly onto the detector inside the batch injection cell. Paper was slightly evaluated coupled to FIA, and no reports were found associated with BIA. Still, it can potentially reduce the BIA manifold by removing the batch injection cell based on the capillarity properties to disperse the injected solution over the detection system. Hence, this article reported the first work coupling batch-injection analysis and microfluidic paper-based analytical device (BIA-μPAD) with pencil-drawn electrodes directly attached to the paper using a CO2 laser pre-treated chromatographic paper. The laser pretreatment of the paper (optimized conditions: 6.5% laser power, 12mms-1 scan rate, and 12mm output distance) was essential to enhance the electrochemical response for ferri/ferrocyanide redox couple and paracetamol (PAR), as shown by spectroscopic and electrochemical techniques. The proposed BIA-μPAD was evaluated using pharmaceutical paracetamol samples as proof-of-concept (optimized conditions: 15μL injected volume and 6.4μLs-1 dispensing rate), obtaining good linearity (R=0.9961) and recovery values ranging from 95 to 103%. Repeatability (n=16) and reproducibility (n=9) tests with 1mmolL-1 PAR also presented well relative standard deviation (RSD) results of 5.1% and 6.6%, respectively. A sampling frequency of 76 h-1 was obtained, which is a similar value compared with conventional BIA apparatus. Limits of detection and quantification were estimated in 0.046 and 0.154mmolL-1, respectively. Additionally, an improvement in the current response and the sample throughput was observed when comparing FIA and BIA-μPADs, attesting the applicability of the proposed device and opening for new possibilities related to paper-based devices coupled with flow techniques.

A Multi-Core Fibre Photonic Lantern-Based Spectrograph for Raman Spectroscopy

We report on the development of a compact (volume $\approx$ 100\:cm$^3$), multimode diffraction-limited Raman spectrograph and probe designed to be compact as possible. The spectrograph uses `off the shelf' optics, a custom 3D-printed two-part housing and harnesses a multi-core fibre (MCF) photonic lantern (multimode to few-mode converter), which slices a large 40~\textmu m multimode input into a near-diffraction-limited 6~\textmu m aperture. Our unique design utilises the hexagonal geometry of our MCF, permitting high multimode collection efficiency with near-diffraction-limited performance in a compact design. Our approach does not require a complex reformatter or mask and thus preserves spectral information and throughput when forming the entrance slit of the spectrograph. We demonstrate the technology over the interval 800~nm to 940~nm (200~cm$^{-1}$ to 2000~cm$^{-1}$) with a resolution of 0.3\:nm (4\:cm$^{-1}$), but other spectral regions and resolutions from the UV to the near infrared are also possible. We demonstrate the performance of our system by recording the Raman spectra of several compounds, including the pharmaceuticals paracetamol and ibuprofen.

Facile HPTLC-densitometric determination of ertapenem and paracetamol in pharmaceuticals and rabbit plasma with pharmacokinetic insights

Simultaneous chromatographic determination of both ertapenem (ERP) and paracetamol (PCL) was achieved for the first time via a new HPTLC-densitometric method. The developed method relied on a simple planar chromatographic separation by mixture of acetonitrile and water (35:15, v/v) and dual-wavelength detection at λmax of both drugs (294 and 247 nm for ERP and PCL, respectively). The Rf values were 0.74 ± 0.05 and 0.88 ± 0.05 for ERP and PCL, respectively. Under the optimized conditions, the linearity range was 40.0–600.0 and 15.0–200.0 ng band−1 for ERP and PCL, respectively with good correlation coefficients (0.9997 and 0.9998 for ERP and PCL, respectively). The LOD were 13.08 and 3.65 ng band−1 for ERP and PCL, respectively. The method validation parameters were in compliance with the international standards. The developed method was enough sensitive and selective for the determination of ERP in the presence of its open beta-lactam ring degradation product, which makes it a suitable stability-indicating method. Consequently, it was successfully applied for pharmaceutical formulation, spiked and real plasma samples of healthy rabbits for real pharmacokinetic studies of ERP and PCL.

A simple, fast method for the analysis of 20 contaminants of emerging concern in river water using large-volume direct injection liquid chromatography-tandem mass spectrometry.

A fast and sensitive method for the determination of a structurally and physico-chemically diverse group of contaminants of emerging concern (CEC) based on large-volume direct injection liquid chromatography-tandem mass spectrometry was developed. The method can be used to determine 20 CECs belonging to different pollutant families (pharmaceuticals, personal care products, and pesticides) in river water at nanogram per liter. A single analytical run is required and the positive and negative ionization modes can be used simultaneously. Because of the large-volume injections of samples and the high sensitivity of the current mass spectrometers, the method has no need of a preconcentration step. The analytes are quantitated with matrix-matched calibration curves. The estimated limits of detection were in the range 0.1-5ngL-1. The accuracy of the method was in the range 86-114%, and the precision, expressed as a relative standard deviation (RSD %), was below 18% for all the analytes (n = 5, at 5, 10, and 25ngL-1). The method was applied to water samples taken from different points along the lower course of the Ebro River, Spain. A total of 12 out of the 20 target analytes were detected, and the ones at higher concentrations were caffeine and the pharmaceuticals paracetamol and ibuprofen (184.8ngL-1, 63.3ngL-1, and 23.3ngL-1, respectively).

Reliable calibration by nonlinear standard addition method in the presence of additive interference effects

The possibility of adapting the Standard Addition Method (SAM) to calibration in very difficult analytical conditions, namely when there is a need to determine an analyte with the use of nonlinear calibration graph and in the presence of matrix components causing additive interference effect, is investigated. To this aim the SAM in the common version and the Chemical H-point Standard Addition Method (C-HPSAM) realized by the flow injection technique were applied. Specifically, a flow manifold was used for construction of a set of nonlinear calibration graphs in different chemical conditions. As the graphs were intersected indicating both the additive interference effect and the analytical result free of this effect, the analyte concentration in the sample was able to be obtained with improved accuracy. The applicability of this approach was verified on the example of spectrophotometric determination of paracetamol in pharmaceuticals and of total acidity in wines. The C-HPSAM method enabled complete compensation of the additive effect and obtaining analytical results at a relative error not exceeding 6.0%.Graphical abstract

Graphene-polyaniline modified electrochemical droplet-based microfluidic sensor for high-throughput determination of 4-aminophenol

We report herein the first development of graphene-polyaniline modified carbon paste electrode (G-PANI/CPE) coupled with droplet-based microfluidic sensor for high-throughput detection of 4-aminophenol (4-AP) in pharmaceutical paracetamol (PA) formulations. A simple T-junction microfluidic platform using an oil flow rate of 1.8 μL/min and an aqueous flow rate of 0.8 μL/min was used to produce aqueous testing microdroplets continuously. The microchannel was designed to extend the aqueous droplet to cover all 3 electrodes, allowing for electrochemical measurements in a single droplet. Parameters including flow rate, water fraction, and applied detection potential (Edet) were investigated to obtain optimal conditions. Using G-PANI/CPE significantly increased the current response for both cyclic voltammetric detections of ferri/ferrocyanide [Fe(CN)6]3−/4− (10 times) and 4-AP (2 times), compared to an unmodified electrode. Using the optimized conditions in the droplet system, 4-AP in the presence of PA was selectively determined. The linear range of 4-AP was 50–500 μM (R2 = 0.99), limit of detection (LOD, S/N = 3) was 15.68 μM, and limit of quantification (LOQ, S/N = 10) was 52.28 μM. Finally, the system was used to determine 4-AP spiked in commercial PA liquid samples and the amounts of 4-AP were found in good agreement with those obtained from the conventional capillary zone electrophoresis/UV–Visible spectrophotometry (CZE/UV–Vis). The proposed microfluidic device could be employed for a high-throughput screening (at least 60 samples h−1) of pharmaceutical purity requiring low sample and reagent consumption.

Degradation of Paracetamol by Fenton-Like Process in Conjunction with Sonication

The degradation of the pharmaceutical paracetamol by using Fenton-like process in conjunction with ultrasonic cavitation was investigated. An evident synergistic effect was found in the combination of sonication and Fenton-like process. Through the application of Response Surface Methodology optimization, the optimum conditions for the degradation of paracetamol were initial pH 3.0, H2O27.0 mmol·L-1and sponge iron 4 g·L-1with acoustic power of 200 W. Under these parameters could obtain 99% degradation of 100mg·L-1paracetamol solution within 30 min treatment.

Supporting of pristine TiO2 with noble metals to enhance the oxidation and mineralization of paracetamol by sonolysis and sonophotolysis

Pharmaceutical residues in fresh water bodies are of significant environmental concern due to their undesirable effects on aquatic organisms at very low concentrations. The present study is about the elimination and overall degradation of a common anti-inflammatory pharmaceutical-paracetamol (PCT) in water by catalytic oxidation using high-frequency ultrasound, UV-irradiation (254nm) and both. The catalysts were synthesized sonolytically by the reduction of Pd and Au to the zero-valent state followed by immobilization of the nanoparticles on the surface of commercial TiO2 (P-25) to improve the activity of the semiconductor under ultrasonic and UV irradiation. It was found that sonolytic oxidation of PCT during catalysis with Pd–TiO2 and Pd/Au–TiO2 was very effective owing to the significantly smaller size of these particles (than that of Au–TiO2), which promoted the formation and collapse of cavitation bubbles on their surface and the incidence of solute contact with the active sites. The addition of persulfate further enhanced the rate of PCT decay, signifying the role of ultrasound in activating the reagent and that of radical-initiated oxidation reactions in the decomposition of the parent compound. The activity of P-25 was low and almost equal under sonolysis and photolysis, but considerably higher under sono-photolysis, where the unfavorable properties of the semiconductor were minimized via combined effects of the two processes. Hybridization also induced a considerable synergy in carbon-mineralization, which was relatively low with single processes. The results were attributed to minimization of electron-hole pair recombination, surface corrosion and competition for photons and radical species. Au-supported particles exhibited higher activity in the presence of UV-irradiation than ultrasound, which was attributed to the unique activity of gold in the UV–vis region. Finally, Pd–TiO2 was found to be the most stable nanocomposite in terms of the ease of recovery and the efficiency of reuse.

Modelling the photo-Fenton oxidation of the pharmaceutical paracetamol in water including the effect of photon absorption (VRPA)

A new model is proposed for the photo-Fenton oxidation of water contaminants including the effect of photon absorption (volumetric rate of photon absorption, VRPA), the effect of the geometry of the reactor and the illuminated volume to total volume ratio (Ri) in the reaction system. Fe(III) was found to be the main species in the aqueous solution responsible for photon absorption provided that hydrogen peroxide was not totally consumed. Paracetamol was used as model pollutant at a concentration of 1mM to validate the model. The illuminated part of the raceway reactor configuration (total length of 80cm) was operated at two liquid depths (5.0 and 2.5cm) equivalent to two irradiated reactor volumes (2 and 1L) and using Ri ratios in the range 0.30–0.65, which changed the dark reactor volume. These values are commonly found in photo-Fenton pilot plants for water treatment and purification. The model successfully fitted the temporal evolution of the dissolved oxygen (O2) and the hydrogen peroxide (H2O2) concentrations and the evolution of the total organic carbon (TOC) in solution in both reactor geometries and for different illuminated volume to total volume ratios. The model can be easily extended to model other water contaminants and provides a robust method for process design, process control and optimization.

Modification of electrodes using conductive porous layers to confer selectivity for the voltammetric detection of paracetamol in the presence of ascorbic acid, dopamine and uric acid

A glassy carbon electrode (GCE) has been modified with multiwalled carbon nanotubes (MWCNTs) for the selective detection of paracetamol (PAR) in the presence of ascorbic acid (AA), dopamine (DA) and uric acid (UA). The oxidation of PAR shows a quasi-reversible response on a naked GCE at which an appreciable overpotential is required to drive the two electron oxidation. However, the peak-to-peak separation is seen to reduce and the electrochemical signal appears more reversible as the GCE is modified with an increasingly thick layer of MWCNTs. The results indicate that both anodic and cathodic peaks occur at lower overpotential with increasing layer thickness on the electrode surface, and that the overall peak-to-peak separation decreases as a result. The data are consistent with a transition from planar diffusion to a thin layer character as the potential required for the oxidation of PAR shifts to lower potentials. The experimental results show that the use of conducting porous layers on the surface of electrodes can be utilised to modify the mass transport regime from planar diffusion to a thin layer character that this alteration can also favourably facilitate the electrochemical discrimination between species which oxidise or reduce at similar potentials under planar diffusion conditions. The modified electrode was used for the determination of PAR using square wave voltammetry in 0.1M phosphate buffer solution (PBS) at pH 7. The results showed that the peak currents were proportional to the concentrations of PAR with a linear dynamic range of 2.0×10−10M to 1.5×10−5M and a detection limit of 9.0×10−11M was obtained. The method has successfully been applied for the determination of PAR in pharmaceuticals.

Intercalation of paracetamol into the hydrotalcite-like host

Hydrotalcite-like compounds are often used as host structures for intercalation of various anionic species. The product intercalated with the nonionic, water-soluble pharmaceuticals paracetamol, N-(4-hydroxyphenyl)acetamide, was prepared by rehydration of the Mg–Al mixed oxide obtained by calcination of hydrotalcite-like precursor at 500 °C. The successful intercalation of paracetamol molecules into the interlayer space was confirmed by powder X-ray diffraction and infrared spectroscopy measurements. Molecular simulations showed that the phenolic hydroxyl groups of paracetamol interact with hydroxide sheets of the host via the hydroxyl groups of the positively charged sites of Al-containing octahedra; the interlayer water molecules are located mostly near the hydroxide sheets. The arrangement of paracetamol molecules in the interlayer is rather disordered and interactions between neighboring molecules cause their tilting towards the hydroxide sheets. Dissolution tests in various media showed slower release of paracetamol intercalated in the hydrotalcite-like host in comparison with tablets containing the powdered pharmaceuticals.

Does Impurity-Induced Step-Bunching Invalidate Key Assumptions of the Cabrera−Vermilyea Model?

We show that the growth recovery mechanism of the {110} faces on crystals of the pharmaceutical paracetamol in the presence of its intrinsic impurity acetanilide occurs in the same way as in the growth of inorganic KH 2 PO 4 (KDP) crystals with Fe(III) and Al(III) impurities, by initial movement of macrosteps while elementary steps remain pinned. This suggests that the mechanism of recovery by activation of elementary step motion assumed by Cabrera and Vermilyea (C-V) is not applicable to a diverse set of common and technologically important crystal systems. Recognizing that impurity-driven macrostep formation depends on an imbalance in the concentration ahead and behind the step, we propose a general condition that must be met for a crystal-impurity system to behave according to the C-V predictions.

Fluorimetric SIA optosensing in pharmaceutical analysis: Determination of paracetamol

The coupling of sequential injection analysis (SIA) and fluorimetric solid phase transduction is here applied to the determination of paracetamol in pharmaceuticals. The reaction product between the analyte and sodium nitrite in acidic medium is inserted, after alkalinization, in the system. This product is transitorily retained on the active solid sensing phase (the anionic solid support QAE A-25) developing its native fluorescence signal, which is measured at 325/430 nm for the excitation and emission wavelengths respectively. The described system is linear within the range 6.6–80 μg ml −1, with a 2 μg ml −1 detection limit and a 2.5% R.S.D ( n = 10). The proposed fluorimetric SIA optosensor has been applied to the determination of paracetamol in several pharmaceutical preparations, obtaining satisfactory results.

Optimization of a capillary zone electrophoresis method by using a central composite factorial design for the determination of codeine and paracetamol in pharmaceuticals

Capillary zone electrophoresis was optimized to quantitatively determine codeine and paracetamol via central composite factorial design. Critical parameters (concentration, buffer, pH, voltage) assessed effects on resolution, analysis time and efficiencies. Optimum separation conditions were achieved using phosphate buffer 20 mM (pH 6.8) and voltage (15 kV). The optimized procedure easily determined codeine and paracetamol with separation in less than 3 min. Calibration curves (R > 0.999) were prepared, with LODs of 13.5 and 340 ng mL(-1) for codeine and paracetamol, respectively, and a good R.S.D.% (<3%). This method was applied to determine codeine and paracetamol in pharmaceutical formulations; recoveries coincided with stated contents.

Determination of Critical Supersaturation from Microdroplet Evaporation Experiments

In this work, we identified a single critical supersaturation, the level of supersaturation above which nucleation will occur instantaneously, for each of a range of compounds: the amino acids glycine and l-histidine, the pharmaceutical paracetamol, the inorganic compound silicotungstic acid (STA), and the protein hen egg white lysozyme (HEWL). Using an evaporation-based microdroplet crystallization platform, we measured the time required to visually detect the first crystal. Crystals were observed to form at increasingly higher levels of supersaturation as the rate of evaporation was increased or as the initial solute concentration was reduced. Through extrapolation of all data of each compound to a nucleation time of zero, we identified a single point of high concentration, the critical supersaturation, which we found to be independent of the rate of solvent evaporation. Using the classical nucleation theory and thermodynamics, we correlated this critical supersaturation with surface tension between th...

Determination of paracetamol in pure and pharmaceutical dosage forms by pulse perturbation technique

A new procedure for kinetic determination of paracetamol in pharmaceuticals is proposed. The method is based on potentiometric monitoring of the concentration perturbations of the matrix reaction system being in a stable non-equilibrium stationary state close to the bifurcation point. In the case considered as the matrix system, the Bray–Liebhafsky oscillatory reaction is used. The response of the matrix system to the perturbations by different concentrations of paracetamol is followed by a Pt-electrode. Proposed method relies on the linear relationship between maximal potential shift, Δ E m, and the logarithm of added paracetamol amounts. It is obtained in optimized experimental conditions for variable amounts of paracetamol in the range 0.0085 and 1.5 μmol. The sensitivity and precision of proposed method were quite good (0.0027 μmol as the limit of detection and 2.4% as R.S.D.). Some aspects of possible chemical interactions between paracetamol and matrix are discussed. Applicability of the proposed method to the direct determination of paracetamol in pharmaceutical formulations was demonstrated.

Continuous flow spectrophotometric determination of paracetamol in pharmaceuticals following continuous microwave assisted alkaline hydrolysis

This paper reports a continuous flow-based spectrophotometric method for the determination of paracetamol in pharmaceuticals. Dilute samples containing paracetamol are continuously hydrolysed in an alkaline medium, using a household microwave oven, to p-aminophenol, which reacts with o-cresol in 3.5 M NaOH. The blue derivative thus formed exhibits an absorbance maximum at 620 nm. The detection limit of the method is 0.2 μg ml −1 and the system obeys Beer's law from 0.6 to 20 μg ml −1. Repeatability was checked by calculating the R.S.D. for 11 standard solutions containing a paracetamol concentration of 4 μg ml −1 each and found to be 1.8%. The proposed method was validated by determining paracetamol in various pharmaceutical preparations with average R.S.D. of 2.4%.

Fast determination of paracetamol by using a very simple photometric flow-through sensing device

A simple flow-through UV optosensing device was developed for the determination of paracetamol based on its transient retention and concentration on a suitable active solid support (Sephadex QAE A-25 anion-exchange resin) packed in the flow cell and the continuous monitoring of its native absorbance on the solid phase at 264 nm. The sample was injected into a 0.08-M NaCl carrier stream at pH 11.0 by using a simple monochannel FIA manifold. After developing the analytical signal, paracetamol was desorbed from the solid support by the carrier solution itself. A very good linear response was found in the concentration range 0.5–8.0 μg ml −1 with a RSD (%) of 1.24, a detection limit of 0.022 μg ml −1 and a sampling rate of 40 h −1. A strong increase in sensitivity as well as a very much higher selectivity were achieved as compared with the conventional flow injection method as a consequence of the separation of the analyte from the sample plug and its retention on the active solid support placed in the detection area. Applicability of the proposed sensor to direct determination of paracetamol in pharmaceuticals (to solve the sample being the only treatment) was successfully demonstrated.

Determination of paracetamol in dosage forms by non-suppressed ion chromatography

An ion-chromatography procedure for the simultaneous determination of paracetamol and salicylic acid without suppression using UV detection is proposed. The method is applied to the determination of paracetamol in pharmaceuticals and also permits the quantitation of the total acetylsalicylic acid as salicylic acid.