REPORT: IR study of degradation of acetaminophen by iron nano-structured catalyst.

Full degradation of acetaminophen (paracetamol) in aqueous solution was investigated at room temperature through heterogeneous iron nano-structured as catalyst in this article. Iron Nano-structured was prepared through simple hydrothermal processes using Iron oxide (Fe2O3) as precursor. The catalytic activity of as prepared Nano-catalyst (NC) was investigated in the degradation of the acetaminophen as an environmental pollutant, commonly called paracetamol, under different operating parameters like pH, dosages of acetaminophen and dose of NC. Remarkable differences in IR spectra were observed after reaction which showed complete degradation of 15 ppm of Acetaminophen using 0.1 g of nano-structured with the recovery of NC followed by its activity four times with full catalytic performance.

A novel nanostructured poly(thionine)-deep eutectic solvent/CuO nanoparticle film-modified disposable pencil graphite electrode for determination of acetaminophen in the presence of ascorbic acid.

A new electrochemical sensor based on thionine (TH), an electroactive polymer, and CuO nanoparticle (CuONP)-modified pencil graphite electrode (PGE) has been developed. Poly(thionine) (PTH) was formed on the CuO/PGE surface by electropolymerisation in ethaline deep eutectic solvent (DES) containing acetic acid dopant to form PTHEthaline/CuO/PGE. Cyclic voltammetry, electrochemical impedance spectroscopy, and differential pulse voltammetry were utilized to evaluate the fabrication process, electrochemical properties, and performance parameters of the modified electrodes. The analytical performance of the PTHEthaline/CuO/PGE was evaluated with respect to linear range, limit of detection, repeatability, and reproducibility for the detection of acetaminophen (APAP) by electrooxidation in the presence of ascorbic acid (AA). Analytical parameters such as pH were optimized. The combined use of PTH and CuONP led to enhanced performance towards APAP due to the large electroactive surface area and synergistic catalytic effect, with a wide linear working range and low detection limit. The reliability of the proposed sensor for the detection of APAP was successfully tested in pharmaceutical samples containing APAP and AA, with very good recoveries. Graphical abstract.

[Black particles in plasma and carcinogenic pills]. / Zwarte deeltjes in plasma en kankerverwekkende pillen.

Recently in a national newspaper presumed large hazards in care were described. Visible black particles were seen in blood plasma and a cancerogenic substance was found in paracetamol. Every year 300.000 bags of plasma are produced. The black particles were found in 11 bags of plasma. Possibly one of these was administered. During administration 175 micron filters are used. Presumably remaining particles will be degraded by the mononuclear-phagocytic system. In paracetamol 6 ppm of para-chloroaniline was found. Depending of the limit used by either the ICH or the EFSA this means for patients using lifelong 6 grams of paracetamol a risk off respectively 1: 200.000 or 1:20.000. This risk is neglectable compared of the life time risks of cancer in the population (1:3). Journalists should realize that this exaggerated commentary can lead to real serious risks (taking NSAID's instead of paracetamol) and mistrust in regular care.

Contribution of low-frequency Raman spectroscopy to determine the solubility curves of drugs in polymers: The case of paracetamol/PVP.

A new method for determining solubility lines of drugs in polymers, based on low-frequency Raman spectroscopy measurements, is described and the results obtained by this method are compared with those obtained using a more classical method based on differential scanning calorimetry investigations. This method was applied to the paracetamol/PVP system using molecular and crystalline dispersions (MCD) rather than usual physical mixtures to reach faster the equilibrium saturated states and make the determination of the solubility line more rapid.

Long-term stability of an infusion containing paracetamol, alizapride, ketorolac and tramadol in glass bottles at 5±3°C.

Background and objective: Infusion containing paracetamol, alizapride, ketorolac and tramadol is used after a general anaesthesia in order to limit pain, fever and nausea. Currently, these infusions are prepared according to demand in the anaesthesia unit, but the preparation in advance could improve quality of preparation and time management. The aim of this study was to investigate the long-term stability of this infusion in glass bottles at 5°C ± 3 °C. Method: Five bottles of infusion were stored at 5°C ± 3 °C for 60 days. A visual and microscope inspection were performed periodically to observe any particle appearance or colour change. pH and absorbance at three wavelengths were measured. The concentrations were measured by ultra-high performance liquid chromatography - diode array detection. Results: Multiple verifications were performed during the first 35 days and no crystal, impurity or colour change were observed. At the next time point (42nd day), crystals were visible to the naked eye. pH and absorbance at 350 nm and 550 nm were stable. A slight increase in the absorbance at 410 nm was observed during the study, suggesting that a degradation product could be formed and absorb at this wavelength. The infusion was considered chemically stable while the lower one-sided prediction limit at 95% remains superior to 90% of the initial concentration. Concentration measurements demonstrated that ketorolac and alizapride remained stable in the infusion for 35 days. The stability of tramadol was 28 days. However, degradation of paracetamol was much faster given that concentration has fallen below 90% of the initial concentration after 7 days. Conclusion: Infusion of paracetamol, alizapride, ketorolac and tramadol remains stable for 7 days in glass bottles at 5°C ± 3 °C and could be prepared in advance with these storage conditions.

Three-way analysis of pH-UV absorbance dataset for the determination of paracetamol and its pKa value in presence of excipients.

A three-way analysis method, parallel factor analysis (PARAFAC) model was applied to the pH-absorbance dataset for the simultaneous determination of paracetamol and its acid-base dissociation constant in presence of excipient interference in a syrup formulation without using chemical pretreatment or chromatographic separation step. The UV spectroscopic data matrices of calibration set, validation and unknown samples were obtained from the absorbance measurements at the five different pH media, considering conjugate acid/base properties of the related drug. Their pH-absorbance data matrices were arranged as a cubic data array (wavelength x sample x pH) (425x52x5). Three-way array of pH-absorbance dataset was decomposed into a trilinear set of spectral, pH and relative concentration profiles of paracetamol and excipients in the commercial syrup using PARAFAC model. In the PARAFAC implementation, paracetamol in the commercial syrup formulation and its pKa value were simultaneously predicted from the relative concentration and pH profiles, respectively. In the method validation step of this study, the performance of PARAFAC model was checked by analyzing the validation samples in terms of selectivity, sensitivity, accuracy and precision of the method. The determination results of paracetamol and its pKa value provided from PARAFAC application were compared to those obtained by a newly developed ultra-performance liquid chromatography (UPLC) method, in terms of simplicity, applicability, interpretability with low cost and short analysis time.

Synthesis of bifunctional cabbage flower-like Ho3+/NiO nanostructures as a modifier for simultaneous determination of methotrexate and carbamazepine.

Cabbage flower-like Ho3+/NiO nanostructure (CFL-Ho3+/NiO NSs) with significant electrocatalytic oxidation has been published for the first time. First, structure and morphology of CFL-Ho3+/NiO-NSs have been described by XRD, SEM, and EDX methods. Then, CFL-Ho3+/NiO-NSs have been applied as a modifier for simultaneous electrochemical detection of methotrexate (MTX) and carbamazepine (CBZ). Functions of the modified electrode have been dealt with through electrochemical impedance spectroscopy (EIS). It has been demonstrated that the electrode response has been linear from 0.001-310.0 µM with a limit of detection of 5.2 nM and 4.5 nM (3 s/m) through DPV for MTX and CBZ. Diffusion coefficient (D) and heterogeneous rate constant (kh) have been detected for MTX and CBZ oxidation at the surface of the modified electrode. Moreover, CFL-Ho3+/NiO-NS/GCE has been employed for determining MTX and CBZ in urine and drug specimens. Outputs showed the analyte acceptable recovery. Therefore, the electrode could be applied to analyze both analytes in drug prescription and clinical laboratories. Graphical abstract Electrochemical sensor based on bifunctional cabbage flower-like Ho3+/NiO nanostructures modified glassy carbon electrode for simultaneous detecting methotrexate and carbamazepine was fabricated.

A Novel Acetaminophen Soft-Chew Formulation Produced via Hot-Melt Extrusion with In-line Near-Infrared Monitoring as a Process Analytical Technology Tool.

Patients who suffer from dysphagia have difficulty in swallowing hard tablets and capsules; hence, gelatin-based soft-chew dosages are used as an alternative and novel drug delivery approach to overcome this problem. However, the conventional method of producing gelatin-based soft-chew dosages has many potential issues. The objective of this study was to use glycerol and the hot-melt extrusion technique to address potential issues and optimize the formulation. Gelatin, acetaminophen, saccharin, xylitol, and sodium chloride and six different ratios of water and glycerol were used in the seven formulations. Extrusion process temperature of formulations 1-6 and formulation 7 were 90°C and 140°C, respectively. Near-infrared spectra were collected during extrusion to monitor quality consistency. Scanning electron microscopic images of the cross-section of the soft-chew dosages were recorded. Differential scanning calorimetry (DSC) was used to characterize the crystal states of each formulation. Texture profile analysis was used to evaluate the physical properties of the tablets. In vitro drug release characteristics were studied. A 45-day stability study was carried out to evaluate the stability of each formulation. Near-infrared spectra showed that formulations 1-6 were uniform while formulation 7 was not. From the DSC results, formulations 1 and 2 showed crystallinity of acetaminophen. Formulation 5 displayed the desired physical and chemical stability in texture profile analysis and in the in vitro drug release studies. By using glycerol and hot-melt extrusion, the potential issues of conventional methods were successfully addressed.

A highly sensitive sensor based on a computer-designed magnetic molecularly imprinted membrane for the determination of acetaminophen.

In this paper, a sensor based on a magnetic surface molecularly imprinted membrane (MMIP) was prepared for the highly sensitive and selective determination of acetaminophen (AP). Before the experiment, the appropriate functional monomers and solvents required for the polymer were screened, and the molecular electrostatic potentials (MEPs) were calculated by the DFT/B3LYP/6-31 + G method. MMIP with high recognition of AP was synthesized based on Fe3O4@SiO2nanoparticles (NPs) with excellent core-shell structure. Next, a carbon paste electrode (CPE) was filled with a piece of neodymium-iron-boron magnet to make magnetic electrode (MCPE), and MMIP/MCPE sensor was obtained by attaching a printed polymer to the surface of the electrode under the strong magnetic. Due to the stable molecular structure of the electrode surface, the sensor is highly effective and accurate for detection of AP using DPV. The DPV response of the sensor exhibited a linear dependence on the concentration of AP from 6 × 10-8 to 5 × 10-5 mol L-1 and 5 × 10-5 to 2 × 10-4 mol L-1, with a detection limit based on the lower linear range of 1.73 × 10-8 mol L-1(S/N = 3). When used for determination of AP in actual samples, the recovery of the sensor to the sample was 95.80-103.76%, and the RSD was 0.78%-3.05%.

MicroNIR/Chemometrics: A new analytical platform for fast and accurate detection of Δ9-Tetrahydrocannabinol (THC) in oral fluids.

BACKGROUND: Δ9-Tetrahydrocannabinol (THC) is already considered one of the most addictive substances since an increasing number of consumers/abusers of THC and THC based products are observed worldwide. In this work, the capabilities of a novel miniaturized and portable MicroNIR spectrometer were investigated in order to propose a practical and intelligible test allowing the rapid and easy screening of Δ9-Tetrahydrocannabinol (THC) oral fluids without any pretreatment. METHODS: Specimens from volunteers were collected in order to consider any sources of variability in the spectral response and spiked with increasing amount of THC in order to realize predictive models to be used in real cases. Partial Least Square-Discriminant Analysis (PLS-DA) and Partial Least Square regression (PLSr) for the simultaneously detection and quantification of THC, were applied to baseline corrected spectra pre-treated by first derivative transform. RESULTS: Results demonstrated that MicroNIR/Chemometric platform is statistically able to identify THC abuse in simulated oral fluid samples containing THC from 10 to 100 ng/ml, with a precision and a sensitivity of about 1.51% and 0.1% respectively. CONCLUSIONS: The coupling MicroNIR/Chemometrics permits to simplify THC abuse monitoring for roadside drug testing or workplace surveillance and provides the rapid interpretation of results, as once the model is assessed, it can be used to process real samples in a "click-on" device.

Spectrometric Smartphone-Based System for Ibuprofen Quantification in Commercial Dosage Tablets.

A rapid and portable analytical methodology has been developed for ibuprofen (IBU) quantification in commercial dosage tablets using a spectrometric smartphone-based system. The analytical methodology employs point-of-use approaches both for sample preparation and detection, demonstrating its potential utility for portable quality control of pharmaceutical products. In this work, IBU is dissolved in methanol and then treated with a Co(II) aqueous solution, forming a blue complex which is extractable by dispersive liquid-liquid microextraction. Then, the sample's absorption spectrum is directly measured by a spectrometric smartphone-based system using cartridge made of polyoxymethylene for solvent compatibility. The main experimental factors affecting the dispersive liquid-liquid microextraction of Co-IBU complex were optimized using a multivariate analysis. Under optimized conditions, a working range between 20 and 80 µg mL-1 was obtained with a correlation coefficient of 0.996 for 5 calibration points. The limit of detection and limit of quantification obtained were 4 and 12 µg mL-1, respectively. The performance of the proposed methodology was evaluated in commercial tablet dosage forms, and the results demonstrate the ability of the method to determine IBU in samples representative of those used in real-world quality control applications. Recovery values between 97% and 105% were obtained, which are comparable to those obtained via standard titrimetric methodology.

Hyperspectral Raman Line Mapping as an Effective Tool To Monitor the Coating Thickness of Pharmaceutical Tablets.

Protective chemical coatings are deposited on drugs during the manufacturing process for the purpose of controlling the pharmacokinetics of active pharmaceutical ingredients (APIs). Although manufacturers attempt to coat all the tablets uniformly, the film thickness of an individual drug is statistically different and depends on the measuring position of the anisotropic structure, and analytical methods for measuring coating thickness must be robust to statistical and geometrical aberrations. Herein, we demonstrate that a spatially offset Raman-spectroscopy-based line mapping method offered excellent calibration and prediction of the coating thickness of 270 acetaminophen ( N-acetyl-para-aminophenol, paracetamol) tablets. Raman-scattered light resurfaced back from the coating and APIs, and offset-resolved spectra were projected according to the vertical positions in an imaging sensor. The Raman intensity ratio between the coating substance and the inner APIs is a key parameter in the analysis, and its variation with respect to the spatial offset is proportional to the coating thickness and duration. The results of this study have implications for the rapid spectroscopic thickness measurement of industrial products coated with transparent or translucent materials.

Quantifying API polymorphs in formulations using X-ray powder diffraction and multivariate standard addition method combined with net analyte signal analysis.

The direct quantification of Active Pharmaceutical Ingredients in solid formulations is a challenging open issue. A consolidated analytical technique based on X-ray Powder Diffraction is available, being the definitive test for the identification of polymorphs and crystal phases. However, its application for quantitative analysis is hindered by matrix effects: refinement methods (e.g. Rietveld method) require a complete knowledge of samples' composition, while univariate calibration methods require the matrix effect to be studied and severely suffer from the co-presence of crystalline and amorphous phases in the sample. Multivariate analysis is the only way to bypass problems affecting refinements procedures and univariate calibration. In particular, the multivariate standard addition method (SAM) is promising; however, it is straightforward only when the analytical blank (matrix devoid of analyte) is available: in that case SAM is applied by simply extrapolating the SAM model to the matrix experimental signal. In this work, the quantitative analysis of polymorphic forms of Active Pharmaceutical Ingredients based on X-ray Powder Diffraction is performed for the first time by a method based on multivariate standard addition method combined with net analyte signal procedure; it allows for reliable quantification of polymorphs of active principles in solid formulations, which are rapidly analyzed without any sample pre-treatment. Two test cases are presented: quantification of two polymorphs of piracetam in binary mixtures (forms II and III), and quantification of paracetamol (form I) in Tachifludec®.

Association Between Meconium Acetaminophen and Childhood Neurocognitive Development in GESTE, a Canadian Cohort Study.

Acetaminophen is the only over-the-counter pain reliever that is not contraindicated during pregnancy, but recent studies have questioned whether acetaminophen is safe for the fetus, particularly the developing brain. This prospective birth cohort study probed the previously observed association between in utero exposure to acetaminophen and neurodevelopment by using concentrations of acetaminophen measured in meconium, which more objectively captures exposure of the fetus than maternal report. Exposure, measured by liquid chromatography coupled with tandem mass spectrometry, was categorized into nondetection, low detection, and high detection levels. At age 6-8 years, children completed a set of subtests from the Wechsler Intelligence Scale for Children, 4th edition. Additionally, this study examined potential effect modification by child sex on the association between acetaminophen exposure and neurodevelopment. In fully adjusted models, in utero exposure to acetaminophen was not statistically significantly associated with decreased scores on any of the examined subtests in all children combined (n = 118). The effect of in utero acetaminophen exposure on the Coding subtest was marginally significantly different among boys and girls, with girls performing significantly better on the task with higher levels of acetaminophen compared with girls with undetectable levels of exposure (ßgirls, low = 2.83 [0.97, 4.70], ßgirls, high = 1.95 [-0.03, 3.93], ßboys, low = .02 [-1.78, 1.81], ßboys, high = -.39 [-2.09, 1.31], pinteraction = .06). Effect modification by child sex was not observed on other subtests. These results do not support prior reports of adverse neurodevelopmental effects of in utero exposure to acetaminophen.

Adverse reaction and rational use of paracetamol tablets and its drug content detection based on spectral test.

Paracetamol and amantadine hydrochloride tablet is a commonly used drug to relieve the common cold. Its main ingredient is 4-Acetamidophenol. The safety of acetaminophen containing cold drugs has attracted more and more attention in recent years. In order to promote the clinical safety of drugs, the adverse reaction and clinical application of acetaminophen drugs are analyzed in this paper. The adverse reactions induced by acetaminophen mainly include: allergic reaction (46.1%), liver and kidney injury (25%), blood system (15.7%) and digestive system (5.2%). At the same time, we tested the content of acetaminophen by using spectral test. It can be seen that the method can be extended to the quantitative analysis and quality control of the effective components of other compound drugs.

Enhanced amperometric detection of paracetamol by immobilized cobalt ion on functionalized MWCNTs - Chitosan thin film.

In the present study, a nanocomposite of f-MWCNTs-chitosan-Co was prepared by the immobilization of Co(II) on f-MWCNTs-chitosan by a self-assembly method and used for the quantitative determination of paracetamol (PR). The composite was characterized by field emission scanning electron microscopy (FESEM) and energy dispersive x-ray analysis (EDX). The electroactivity of cobalt immobilized on f-MWCNTs-chitosan was assessed during the electro-oxidation of paracetamol. The prepared GCE modified f-MWCNTs/CTS-Co showed strong electrocatalytic activity towards the oxidation of PR. The electrochemical performances were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). Under favorable experimental conditions, differential pulse voltammetry showed a linear dynamic range between 0.1 and 400 µmol L-1 with a detection limit of 0.01 µmol L-1 for the PR solution. The fabricated sensor exhibited significant selectivity towards PR detection. The fabricated sensor was successfully applied for the determination of PR in commercial tablets and human serum sample.

A new analytical device incorporating a nitrogen doped lanthanum metal oxide with reduced graphene oxide sheets for paracetamol sensing.

The novel N-CeO2 nanoparticles decorated on reduced graphene oxide (N-CeO2@rGO) composite has been synthesized by sonochemical method. The characterization of as prepared nanocomposite was intensely performed by UV-Vis, FT-IR, EDX, FE-SEM, HR-TEM, XRD, and TGA analysis. The synthesized nanomaterial was further investigated for its selective and sensitive sensing of paracetamol (PM) based on a N-CeO2@rGO modified glassy carbon electrode. A distinct and improved reversible redox peak of PM is obtained at N-CeO2@rGO nanocomposite compared to the electrodes modified with N-CeO2 and rGO. It displays a very good performance with a wide linear range of 0.05-0.600 µM, a very low detection limit of 0.0098 µM (S/N = 3), a high sensitivity of 268 µA µM-1 cm-2 and short response time (<3 s). Also, the fabricated sensor shows a good sensibleness for the detection of PM in various tablet samples.

A voltammetric sensor for acetaminophen based on electropolymerized-molecularly imprinted poly(o-aminophenol) modified gold electrode.

A simple and reliable molecularly imprinted polymer (MIP) based voltammetric sensor has been proposed for the determination of acetaminophen (AP). Gold nanoparticles (AuNPs) were initially deposited on the surface of gold electrode (GE) so as to get amplified electrochemical signals. Subsequently, a MIP film was created on the AuNPs modified GE (AuNPs/GE) surface by electropolymerization of o-aminophenol in the presence of AP as the template molecule. Significant parameters governing the performance of the sensor were studied and optimised. The proposed sensor presented a linear behaviour between peak current and concentration of AP in the range 4.5 × 10-5-5.0 × 10-7M with the limit of detection being 2.3 × 10-9M. The developed MIP/AuNPs/GE based sensor is simple in preparation and showed excellent selectivity, reproducibility and was successfully applied for the analysis of AP in pharmaceutical formulations and physiological fluids.

Suicide by Medication Overdose in Prison: A Study of Three Cases.

Suicide is one of the principal causes of mortality in a prison environment. Although suicide by medication overdose is less frequent than suicide by hanging, self-strangulation, or vein cutting, it raises questions as to how the medications are obtained, particularly in view of the specific organization of the medication circuit in prisons. We present three cases of suicide by medication overdose involving different therapeutic classes with different distribution circuits and review the regulatory requirements and the measures that could be taken to prevent such suicides.

Toxic Myocarditis Caused by Acetaminophen in a Multidrug Overdose.

We report the case of an 18-year-old woman with personality disorders who was hospitalized a few hours after suicidal ingestion of acetaminophen, quetiapine, acetylsalicylic acid, and ethanol. Twelve hours after admission, severe liver damage was evident, but the patient was stable and awaiting hepatic transplantation. Electrolytes were successfully controlled. The condition of the liver stabilized. Cardiac biomarkers then deteriorated unexpectedly. Localized ST-segment elevations were noted on electrocardiogram, but angiography ruled out myocardial infarction. A computed tomographic scan ruled out cerebral edema. The patient died of irreversible cardiac arrest 40 hours after admission. Heart failure remained unexplained, and the body underwent forensic autopsy.At autopsy, histologic findings were indicative of acute toxic myocarditis and were concluded to be caused by acetaminophen intoxication. Acetaminophen overdose is common and typically leads to liver failure requiring supportive treatment and emergency liver transplantation. Toxic myocarditis is an extremely rare complication of acetaminophen overdose. It has only been reported 4 times in the literature despite the widespread use and misuse of acetaminophen. Toxic myocarditis remains a possibility in many cases of overdose but can be overlooked in a clinical picture dominated by hepatorenal failure and encephalopathy. Clinicians and forensic pathologists should be aware of this rare potential complication.