Paracetamol Concentration Research Articles

Paracetamol, its metabolites, and their transfer between maternal circulation and fetal brain in mono- and combination therapies.

Due to its availability and perceived safety, paracetamol is recommended even during pregnancy and for neonates. It is used frequently alone or in combination with other drugs required for the treatment of various chronic conditions. The aim of this study was to investigate potential effects of drug interactions on paracetamol metabolism and its placental transfer and entry into the developing brain. Sprague Dawley rats at postnatal day P4, pregnant embryonic day E19 dams, and non-pregnant adult females were administered paracetamol (15mg/kg) either as monotherapy or in combination with one of seven other drugs: cimetidine, digoxin, fluvoxamine, lamotrigine, lithium, olanzapine, valproate. Concentrations of parent paracetamol and its metabolites (paracetamol-glucuronide, paracetamol-glutathione, and paracetamol-sulfate) in plasma, cerebrospinal fluid (CSF) and brain were measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and their entry into the brain, CSF and transfer across the placenta were estimated. In monotherapy, concentration of parent paracetamol in plasma, CSF, and brain remained similar and at all ages brain entry was unrestricted. In combination therapies, CSF entry of paracetamol increased following co-treatment with olanzapine. Placental transfer of parent paracetamol remained unchanged, however, transfer of paracetamol-sulfate increased with lamotrigine co-administration. Acutely administered paracetamol was more extensively metabolized in adults compared to younger ages resulting in increased concentration of its metabolites with age. Developmental changes in the apparent brain and CSF entry of paracetamol appear to be determined more by its metabolism, rather than by cellular control of its transfer across brain and placental barriers.

Rapid and non-invasive analysis of paracetamol overdose using paper arrow-mass spectrometry: a prospective observational study

BackgroundParacetamol is the most consumed medicine globally. Its accessibility contributes to common overdose. Paracetamol overdose is responsible for > 50% of acute liver failure cases, making it the second most common reason for a liver transplant. Rapid quantitation of paracetamol is crucial to guide treatment of paracetamol overdose. Current tests require invasive sampling and relatively long turnaround times. Paper arrow-mass spectrometry (PA-MS) combines sample collection, extraction, separation, enrichment and ionisation onto a single paper strip, achieving rapid, accurate, cost-effective and eco-friendly analysis direct from raw human saliva.MethodsTo validate PA-MS against an established test, 17 healthy adults were recruited. Samples were collected before and at 15, 30, 60, 120 and 240 min after ingesting 1 g of paracetamol. Plasma measured with an established clinical test served as the reference standard to validate PA-MS with three biofluids—plasma, resting saliva (RS) and stimulated saliva (SS). Participants’ views of blood, RS and SS sampling procedures were assessed qualitatively. Cross-validation was assessed using Lin’s concordance correlation coefficients (CCC), Bland–Altman difference plots, and ratios of PA-MS to the reference standard test.ResultsPA-MS using stimulated saliva offers a reliable alternative to intravenous blood sampling. The CCC is 0.93, the mean difference with the reference test is − 0.14 mg/L, and the ratios compared to the reference test are 0.84–1.27 from correlated samples collected at 5 intervals over 4 h for each participant.ConclusionsParacetamol detection from SS with PA-MS provides a reliable result that can aid timely treatment decisions. Differences between paracetamol concentration in resting and stimulated saliva were also identified for the first time, highlighting the importance of standardising saliva collection methods in general. This study marks a major milestone towards rapid and convenient saliva analysis.

Population Pharmacokinetics of Intravenous Paracetamol and Its Metabolites in Extreme Preterm Neonates in the Context of Patent Ductus Arteriosus Treatment.

Our aim was to describe the pharmacokinetics of paracetamol and its metabolites in extreme preterm neonates in the context of patent ductus arteriosus treatment. Factors associated with inter-individual variability and metabolic pathways were studied. The association between drug exposure and clinical outcomes were investigated. Preterm neonates of 23-26 weeks' gestational age received paracetamol within 12 h after birth. Plasma concentrations of paracetamol and its metabolites were measured throughout 5 days of treatment. Clinical success was defined as ductus closure on two consecutive days or at day 7. Aspartate aminotransferase and alanine aminotransferase levels were used as surrogates for liver damage. Data from 30 preterm neonates were available for pharmacokinetic analysis. Paracetamol pharmacokinetics were described using a two-compartment model with significant positive effects of weight on clearance and of birth length on peripheral compartment volume. Paracetamol was mainly metabolised into sulphate (89%) then glucuronide (6%), and the oxidative metabolic pathway was reduced (4%). The glucuronidation pathway increased with gestational age, whereas the sulfation pathway decreased. No difference was observed in drug exposure between successful and unsuccessful patients. No increase in aspartate aminotransferase and alanine aminotransferase levels were observed during treatment, and no association was found with either paracetamol or oxidative metabolite exposures. The relative proportions of the metabolic pathways were characterised with gestational age. In the range of observed drug exposures, no association was found with clinical response or liver biomarkers. These findings may suggest that paracetamol concentrations were within the range that already guarantee a maximum effect on ductus closure.

Pharmaceutical Wastewater Treatment Using Activated Carbon in a Fixed-Bed Column

Though beneficial for health, pharmaceuticals have emerged as persistent environmental contaminants over recent decades. Discharges from wastewater treatment plants are a primary source of these pharmaceuticals in natural water bodies, as conventional treatment methods often fail to remove them effectively. Fixed-bed columns with GRANULATED ACTIVATED CARBON (GAC) are widely used in water treatment facilities to eliminate organic micropollutants; however, their efficiency in systematically removing pharmaceutical waste from wastewater still needs to be explored. This study evaluates the performance of a GAC fixed-bed adsorption column for removing ibuprofen, paracetamol, and ciprofloxacin from wastewater, focusing on contact time as a critical parameter. Key Findings: Initial concentrations of ibuprofen, paracetamol, and ciprofloxacin in the wastewater were 0.068 mg/L, 0.08486 mg/L, and 0.068 mg/L, respectively. After 45 minutes, the column achieved removal efficiencies of 100% for ibuprofen, 92.8% for paracetamol, and 67.6% for ciprofloxacin, with no significant changes in concentrations observed at 90 minutes. These results suggest that GAC fixed-bed adsorption columns can rapidly and effectively reduce pharmaceutical concentrations in wastewater, with ibuprofen showing complete removal in under an hour. This study contributes to understanding GAC’s effectiveness in treating pharmaceutical wastewater. It highlights the potential of optimised contact time for efficient removal, underscoring its viability as an industrial treatment option. Keywords: Pharmaceutical wastewater; emerging contaminants, adsorption

Pharmacokinetic profile of novel multi-layer stable effervescent tablet: a cross-over study with an established European brand in healthy young male adults.

Effervescent formulation helps in faster and better absorption of drugs, especially those that are rapidly soluble in water. However, these tablets require special packaging in order to prevent them from absorbing moisture, hence increasing cost. We compared an effervescent tablet prepared using an in-house developed method (multi-layer tablet with acid and base part separated by an inert layer) to a European effervescent tablet (Efferalgan®) in a single-center, randomized cross-over study among twelve healthy volunteers. Blood samples were collected for 8h and analyzed for paracetamol concentration using HPLC. Our results showed that both the products have similar pharmacokinetic profiles with no significant difference observed for Clast, Thalf, Kelim, and MRT (p-value > 0.05). Moreover, to assess bioequivalence we did not find any significant difference (p-value > 0.05) in AUC (27.12 ± 6.02 vs. 27.29 ± 2.64µg.h/ml), Cmax (7.42 ± 1.06 vs. 7.83 ± 1.19µg/ml) and tmax (0.85 ± 0.22 vs. 0.83 ± 0.25h). The TR ratios for AUC, Cmax, and tmax were 0.99, 0.95, and 1.02 respectively, and were all within the specified FDA limits i.e., 0.8-1.25. We found our test tablet to be bioequivalent to that of Efferalgan®.

Augmenting the sensitivity for hepatotoxicity prediction in acute paracetamol overdose: combining psi (ψ) parameter and paracetamol concentration aminotransferase activity multiplication product

Introduction While factors like high serum paracetamol (acetaminophen) concentration and delayed acetylcysteine treatment increase hepatotoxicity risk, existing predictive tools, such as the paracetamol concentration aminotransferase activity multiplication product and the psi (ψ) parameter, lack definitive accuracy. This study evaluated the paracetamol psi parameter multiplication product addition against the psi parameter and the paracetamol concentration aminotransferase activity multiplication product for predicting hepatotoxicity following an acute paracetamol overdose. Methods A retrospective analysis of patients with acute paracetamol overdose from January 2007 to December 2016 was conducted. The paracetamol psi parameter multiplication product addition, calculated by summing the psi parameter (mmol/L × h) and the paracetamol concentration aminotransferase activity multiplication product (g U/L2), was used. Hepatotoxicity was defined as aspartate or alanine aminotransferase activities ≥1,000 U/L. Diagnostic accuracy was assessed through sensitivity, specificity, the area under the receiver operating characteristic curve, and their corresponding 95% CI, with the optimal cutoff determined using the maximum Youden index method. Results The study comprised 421 patients, mostly female (82.9%) with a median age of 23 years. Hepatotoxicity occurred in 13.5% (57 patients). The paracetamol psi parameter multiplication product addition showed an area under the receiver operating characteristic curve of 0.989 (95% CI: 0.974–0.997), with an optimal cutoff at 9.723, providing 96.5% sensitivity and 97.3% specificity. The paracetamol psi parameter multiplication product addition demonstrated superior performance in area under the receiver operating characteristic curve compared to the individual assessments of the psi parameter (0.916; 95% CI: 0.885–0.941) and the paracetamol concentration aminotransferase activity multiplication product (0.901; 95% CI: 0.868–0.928). Discussion The paracetamol psi parameter multiplication product addition appears to be a more effective diagnostic tool than the psi parameter or the paracetamol concentration aminotransferase activity multiplication product alone. Conclusion Incorporating the paracetamol psi parameter multiplication product addition into clinical protocols could improve paracetamol overdose management by enabling precise identification of individuals at heightened risk for hepatotoxicity, thereby facilitating the customization of treatment approaches.

Post-prandial acyl ghrelin infusion in heart failure patients increases gastric emptying rate

Abstract Background Acyl ghrelin (ghrelin) increases cardiac output (CO) and contractility in patients with heart failure with reduced ejection fraction (HFrEF). In healthy humans, ghrelin increases gastric emptying rate (GER) and hunger, a potential add-on benefit for HFrEF patients suffering from cachexia with symptoms of delayed gastric emptying and loss of appetite. Aim Determine if post-prandial ghrelin infusion increases GER and hunger in HFrEF patients; compare to CO. Methods This study was a component of a double-blind placebo-controlled trial of acyl ghrelin vs. placebo in HFrEF. Patients (n=29) arrived fasted and received a 500 kcal breakfast and 1.5 g paracetamol. They next received placebo (vehicle, n=15) or ghrelin infusion (0.1 µg/kg/min, n=14) for 120 min. Blood was tapped for plasma at 0, 30, 60, 120 and 150 min into the meal. Plasma concentration of paracetamol was measured to assess GER of a liquid bolus. Hunger scores and CO were recorded. Mann-Whitney rank sum test was used for statistics. Results Paracetamol peaked at 30 min in 8 of 14 (57%) in the ghrelin treatment group versus 1 of 15 (7%) in the placebo group (P=0.004, Fig 1). Remaining patients peaked at later time points. There were no anomalous peaks at 0 min baseline or 2880 min (2 days). The ghrelin treatment group data was segregated into rapid (peak at 30 min, n=8) and slow (peak >30 min, n=6) GER subgroups. The rapid subgroup had a ghrelin treatment effect on CO (one-way repeat measures) (P<0.001, Fig 2). Baseline (t=0) CO for the rapid GER subgroup was 4.06 ±1.41 L/min (median ±SD) and 3.95 ±0.62 L/min for the slow GER subgroup (P=0.31). Data points shown are median ± SEM, each patient normalized to own baseline (100%); * P<0.05, ** P<0.01, *** P<0.001, pairwise comparison to baseline. Hunger gradually increased. The greatest increase in hunger was at 150 min, at which time median fold increase in hunger relative baseline was 1.6 (placebo), 1.7 (ghrelin, slow GER) and 2.3 (ghrelin, rapid GER). These hunger differences between groups did not reach significance. However, this trend was consistent with ghrelin induction of hunger, especially in those with potent GER and CO responses. Conclusions Ghrelin increases GER, and potentially hunger, in HFrEF patients in addition to increasing CO. Some HFrEF patients may benefit from this add-on effect.Fig 1.Time of paracetamol peak.Fig 2.Cardiac output.

A Pharmacokinetic Study of the Interaction Between Regorafenib and Paracetamol in Male Rats.

Background: In clinical practice, the prevalent problem of polypharmacy could result in increased risks of drug-drug interactions. Regorafenib (REG) is commonly co-administered with paracetamol (PA) as a treatment protocol in cancer patients with pain therapy. Purpose: This study aimed to demonstrate the effect of paracetamol on the pharmacokinetic parameters of regorafenib and its metabolites following a single administration of both substances in rats. Additionally, the influence of REG and its metabolites on the pharmacokinetics of paracetamol was also determined. Methods: Twenty-four rats were divided randomly into three groups: REG group (IIREG, regorafenib 20 mg/kg, n = 8), PA group (IIIPA, paracetamol 100 mg/kg, n = 8), and REG+PA co-administration group (IREG+PA, REG 20 mg/kg and PA 100 mg/kg, n = 8). The concentrations of regorafenib, regorafenib-N-oxide (M-2), and N-desmethyl-regorafenib-N-oxide (M-5) were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The plasma concentrations of PA and its glucuronide (GPA) and sulfate (SPA) metabolites were measured using the validated high-performance liquid chromatography method with ultraviolet detection (HPLC-UV). The pharmacokinetic parameters were calculated using a non-compartmental model. The statistical evaluation was performed in the SAS program. Results: After the administration of PA, the Cmax and AUC0-∞ of REG increased by 890% and 1140%, respectively; for M-2, they increased by 220% and 170%, and for M-5, by 2130% and 1730% (Cmax and AUC0-∞, respectively). A difference in the ratio of M-2/REG for AUC0-∞ and Cmax between the groups was observed, but not for M-5/REG. The AUC0-∞ for PA and GPA decreased by 20.7% and 51.1%, respectively, when PA was co-administered with REG. But the AUC0-∞ for SPA increased by 91.35% in the IREG+PA group. A difference in the ratio of GPA/PA for Cmax and for SPA/PA for AUC0-t and AUC0-∞ between the groups was observed. Conclusions: Paracetamol increased the plasma exposure of regorafenib, M-2, and M-5, which may exacerbate the drug's side effects. In contrast, REG reduced paracetamol exposure and contributed to its faster elimination, which may reduce the analgesic and antipyretic effects of paracetamol. These findings suggest clinical relevance for oncology patients requiring analgesic treatment.

The impact of updated national guidelines for managing unintentional paediatric liquid paracetamol exposures: a retrospective poisons centre study

Introduction In 2015, Australia and New Zealand treatment guidelines recommended a 2 h paracetamol serum concentration for risk assessment of unintentional paracetamol liquid exposures. We assess our experience with this approach. Methods Retrospective case review of children <6 years-old with liquid paracetamol overdoses referred to a regional poisons information centre January 2017 to August 2022. We extracted data on the exposure and management from the poisons information centre and hospital medical records. We identified additional cases with two paracetamol concentrations obtained from September 2022 to June 2024. Results Of 437 paediatric poisonings, 271 were eligible for inclusion. The median age was 24 months, the median time to presentation was 120 min, and paracetamol was the sole ingestant in 92% of cases. Blood testing was recommended in 131 patients (48.3%), occurring at 2 h post-ingestion in 62 patients (47.3%). Testing at a later time was mostly due to delayed presentation, including to hospitals unable to measure paracetamol concentrations. Eighteen patients (16.7%) had repeat blood testing, and five additional cases were identified in the subsequent period. Overall, the concentration decreased in 19 patients (83%), but in three patients it increased, from 73 mg/L to 81 mg/L (0.49–0.54 mmol/L), from 154 mg/L to 179 mg/L (1.03–1.19 mmol/L), and from 56 mg/L to 115 mg/L (0.37–0.77 mmol/L). Symptomatic patients were more likely to receive a second blood test or acetylcysteine while awaiting investigations. Of 19 patients administered acetylcysteine, it was discontinued in five due to low paracetamol serum concentrations. All patients recovered. Discussion Guidelines were followed in >90% of patients and this testing regimen shortened length of stay. Based on these data, Australian treatment guidelines now recommend repeat testing for 2 h paracetamol serum concentrations >100 mg/L (0.67 mmol/L). Conclusion A paracetamol serum concentration between 2 h and 4 h post-ingestion in children <6 years-old with unintentional poisonings of paracetamol liquid can facilitate medical discharge.

Comparative evaluation of accuracy in near-infrared and Raman spectroscopic determinations of component concentration in packed solid mixtures under various packing densities

BackgroundPhysical characteristics of packed samples, such as packing density, influence subsequent near-infrared (NIR) and Raman spectral features. This potential decrease in accuracy is a concerning issue in practical applications, such as the analysis of pharmaceutical tablets using vibrational spectroscopy. Thus, we compared the accuracy tolerances of both methods under varying packing densities. For evaluation, diffuse reflectance NIR and two different Raman measurements with laser illumination diameters of 1 and 6 mm (referred to as the WAI-1 and WAI-6 schemes, respectively) were used to analyze paracetamol tablets with packing densities of 1.1, 1.17, 1.24, and 1.29 g/cm³. ResultsIn all three measurements, increased packing density resulted in an increase in band intensity and an upward-moving baseline due to the variation in void volume (equivalent to porosity) in the tablets. The Raman spectra acquired using the WAI-6 scheme were less sensitive to packing density variations by averaging out different photon propagations over a large area during spectral acquisition. The accuracies for determining paracetamol concentration using the WAI-6 scheme did not significantly deteriorate when the packing density difference was not large, such as between 1.17 and 1.24 g/cm³ (absolute difference of 0.07 g/cm³). The WAI-6 scheme enabled more robust compositional analysis of the tablets with different packing densities. SignificanceThe WAI-6 Raman scheme provides a more robust compositional analysis of tablets under variations in packing density, making it a preferable choice for practical applications. Using the WAI-6 scheme, an additional effective strategy to minimize accuracy deterioration is further beneficial.

Ecotoxicological effects of paracetamol on the biochemical and molecular responses of spinach (Spinacia oleracea L.)

The widespread use of pharmaceuticals, including paracetamol, has raised concerns about their impact on the environment and non-target species. The aim of this study was to investigate the biochemical and molecular responses of Spinacia oleracea (spinach) to high paracetamol concentrations in order to understand the plant's stress responses and underlying mechanisms. Under controlled conditions, spinach plants were exposed to different paracetamol concentrations (0, 50, 100, and 200 mg/L). The study evaluated the impact of paracetamol exposure on biochemical parameters such as oxidative stress markers (H2O2, MDA), activities of antioxidant enzymes (APX, CAT, GPOD, SOD), levels of non-enzymatic components (phenolics and flavonoids), and phytohormones (ABA, SA, and IAA). Furthermore, the study assessed molecular impacts by analyzing stress-related genetic variation and alterations in the gene expression of the antioxidant enzymes. Results showed that paracetamol exposure significantly increased oxidative stress in spinach, which was evident through the elevated H2O2 and MDA levels. However, the antioxidant defense mechanisms were activated to counteract this effect, as evidenced by increased activity of antioxidant enzymes and higher phenolics and flavonoid levels. Moreover, induction in the phytohormone levels indicated a stress response in paracetamol-treated plants compared to control plants. RAPD analysis revealed polymorphism indicating the DNA damage, and the Real-time qRT-PCR method showed significant upregulation of stress-responsive genes, highlighting the severe impact of paracetamol at the molecular level. The study concludes that high paracetamol concentrations pose a significant threat to spinach growth by affecting both biochemical and molecular processes. These findings underscore the need for strict environmental management practices to mitigate the possible impact of continuous release, accumulation, and long-term exposure of pharmaceutical contaminants to the environment and implement policies to reduce pharmaceutical pollutants to preserve ecological health and biodiversity.

Air Pulsed-Corona discharges for degradation of emerging pharmaceutical pollutants in water and toxicity by-products control

The present study, based a tip-to-plane pulsed corona setup, examined the effects of tip-water distance, radius of curvature of electrode tip, and pulse voltage on the production of liquid-phase RONS used an indicator of degradation performance. Measurements of long-lived RONS species (nitrates, nitrites and H2O2) in deionized water were specifically analyzed. The optimum conditions were used for the removal of a high concentration (500 mg/L) of 4-acetaminophen (i.e. paracetamol) with study of oxidation by-products and their toxicity. The results showed that optimum RONS production in the liquid phase occurred for a short gap distance (4 mm), a tip curvature radius of 100 μm and a pulsed voltage of 10 kV and 10 kHz corresponding to an energetic corona spark regime which is characterized by optical emission spectroscopic measurements. Using these optimal corona discharge parameters, the study showed that after 30 min of exposure to the air plasma, 60 % removal efficiency was achieved at an initial paracetamol concentration of 500 mg/L based on HPLC-DAD sample analysis. GC–MS and LC-MS analysis of treated samples enabled us to identify and characterize two new by-products not previously identified in the literature: N-(4-(4-hydroxyphenylamino) phenyl) acetamide (m/z: 242) and N-(4-aminophenyl) acetamide (m/z: 150), most of which were nitrogen compounds. Further analysis of the toxicity of these by-products to the human cell line (HEK-293) demonstrated that the treated water was not toxic.Overall, these results show that the CDP system is one of the best techniques for treating highly polluted wastewater.

Voltammetric Assessment of Paracetamol on a CuONPs – MWCNTs Modified Glassy Carbon Electrode

In this work, an electrochemical sensor using differential pulse voltammetric method for the assessment of antipyretic and analgesic drug, paracetamol was developed. The CuO nanoparticles were synthesized and characterized. A glassy carbon electrode (GCE) fabricated with the suspension of CuO nanoparticles (CuONPs) and multi-walled carbon nanotubes (MWCNTs) were used. The fabricated electrode was characterized using Potassium ferricyanide as a redox probe, which showed increase in the electro active area in the modified electrode. The modified electrode showed improved anodic peak current enhancement in phosphate buffer solution. The consequence of pH of supporting electrolyte and amount of nanoparticles suspension were investigated at a physiological pH of 7.4. Using differential pulse voltammetry, the fabricated electrode showed linear dynamic range from 9 to 160 nM of paracetamol concentration. From the calibration plot, the computed detection limit was 5.06nM and quantification limit was16.88 nM. The developed method was checked for its reproducibility and assay during a day and intraday as well and the results were good with permitted range of errors. The developed process was fruitfully applied to detect paracetamol in pharmaceutical formulations.

Pharmaceutical Pollution of the English National Parks.

England's 10 national parks are renowned for their landscapes, wildlife, and recreational value. However, surface waters in the national parks may be vulnerable to pollution from human-use chemicals, such as active pharmaceutical ingredients (APIs), because of factors like ineffective wastewater treatment, seasonal tourism, a high proportion of elderly residents, and the presence of low-flow water bodies that limit dilution. The present study determined the extent of API contamination in the English national parks by monitoring 54 APIs in 37 rivers across all national parks over two seasons. Results were compared to existing data sets for UK cities and to concentration thresholds for ecological impacts and antimicrobial resistance selection. Results revealed widespread contamination of the national parks, with APIs detected at 52 out of 54 sites and in both seasons. Thirty-one APIs were detected, with metformin, caffeine, and paracetamol showing the highest mean concentrations and cetirizine, metformin, and fexofenadine being the most frequently detected. While total API concentrations were generally lower than seen previously in UK cities, locations in the Peak District and Exmoor had higher concentrations than most city rivers. Fourteen locations had concentrations of either amitriptyline, carbamazepine, clarithromycin, diltiazem, metformin, paracetamol, or propranolol above levels of concern for fish, invertebrates, and algae or for selection for antimicrobial resistance. Therefore, API pollution of the English national parks appears to pose risks to ecological health and potentially human health through recreational water use. Given that these parks are biodiversity hotspots with protected ecosystems, there is an urgent need for improved monitoring and management of pharmaceutical pollution and pollution more generally not only in national parks in England but also in similar environments across the world. Environ Toxicol Chem 2024;43:2422-2435. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Advanced UV Spectrophotometry-Classical Least Squares Determination of Paracetamol, Phenylpropanolamine HCl, and Chlorpheniramine Maleate in Tablet Dosage Form

This study aims to develop and validate an advanced UV spectrophotometry- Classical Least Squares (CLS) for the simultaneous determination of Paracetamol (PA), Phenylpropanolamine HCl (PH), and Chlorpheniramine Maleate (CH) in tablet dosage form. The method involves the preparation of standard solutions of the three compounds across their respective concentration ranges 3-9 µg/mL for PA, 170-512 µg/mL for PH, and 7-19 µg/mL for CH. The CLS spectrophotometry UV method was applied to these spectra to construct calibration, which were then used to predict the concentrations of PA, PH, and CH in tablet dosage form. Validation of the method demonstrated excellent linearity, precision, and accuracy, with recovery rates of 99.26% for PA, 100.06% for PH, and 99.41% for CH. Sensitivity analysis revealed Limits of Detection (LOD) of 0.10 µg/mL for PA, 1.20 µg/mL for PH, and 0.30 µg/mL for CH, and Limits of Quantification (LOQ) of 0,30 µg/mL for PA, 4.00 µg/mL for PH, and 1.50 µg/mL for CH. The method’s robustness and reliability make it an excellent choice for routine quality control of these compounds in pharmaceutical tablet formulations.

Should high-dose N-acetylcysteine be given in cases of massive paracetamol overdoses: A narrative review.

N-acetylcysteine (NAC) is regarded as an effective treatment of paracetamol overdoses. However, in cases of "massive" paracetamol overdoses, recent studies indicate that patients may not be sufficiently treated with the standard dose of NAC (300 mg/kg over 20-21 h). The subject is further complicated because "massive overdoses" and "high-risk" are defined differently; some studies use the ingested amount (e.g., >40 g), and some studies use blood concentrations of paracetamol and transaminases. This narrative review investigates whether high-dose NAC significantly decreases the risk of hepatotoxicity in patients with massive paracetamol overdoses. Three observational studies were analysed; one study with 373 patients found no significant difference (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 0.49-3.29). One study with 79 patients found a significant difference (OR: 0.27, 95% CI: 0.08-0.94). The third study with 89 patients found a significant difference in hepatoxicity between the groups (p= 0.043). There are no solid evidence to support that treatment with high-dose NAC significantly reduces the rate of hepatotoxicity in patients presenting with massive paracetamol overdoses. Differences in inclusion criteria in the included studies make the studies incomparable. This paper shows that standardized inclusion is needed to determine whether a high-dose NAC regimen should be included in clinical practice.

Synthesis of Copper Molybdate and Its Electrochemical Sensing of Paracetamol.

Background In recent years, significant advancements have been made in various scientific sectors, particularly in healthcare and pharmaceutical research. This progress has been driven by the development of enhanced sensing materials and methodologies. Electrochemical sensing has become an important tool in detecting and analyzing drug molecules due to its high sensitivity, specificity, and rapid response times. Among various drugs, paracetamol, also known as acetaminophen, is widely used for its analgesic and antipyretic properties. Accurate detection of paracetamol is crucial due to its widespread use and potential for overdose, which can lead to severe liver damage.Copper molybdate (CuMoO4) is a transition metal oxide that has garnered attention for its excellent electrical conductivity and electrochemical stability. These properties make it a promising candidate for use in electrochemical sensors. The ability of CuMoO4 to act as a sensor material is enhanced by its unique structural and morphological characteristics, which can be tailored during synthesis. Aim This study aimed to synthesize CuMoO4 and investigate its electrochemical sensing capability for the detection of drug molecules, specifically paracetamol. Materials and method CuMoO4 was synthesized using a precipitation method that did not involve any surfactants. This approach was chosen to simplify the synthesis process and avoid potential contamination from surfactants. The morphology of the synthesized CuMoO4 nanoparticles was investigated using a field emission scanning electron microscope (FE-SEM). Energy-dispersive X-ray spectroscopy (EDX) confirmed the purity of the CuMoO4 nanomaterial. Structural analysis was performed using X-ray diffraction (XRD). To evaluate the electrochemical sensing capability of CuMoO4for paracetamol, Differential pulse voltammetry (DPV) was employed. DPV is a sensitive electrochemical technique that can detect changes in current response corresponding to the presence of analytes. Results The synthesized CuMoO4exhibited a rock-like structure, as revealed by FE-SEM imaging. This morphology is advantageous for electrochemical applications due to the increased surface area available for interaction with analytes. EDXconfirmed the purity of the CuMoO4nanomaterial, showing no significant impurities. XRD analysis indicated that the CuMoO4nanoparticles were crystalline in nature, which is beneficial for consistent and reproducible electrochemical behavior. The DPV analysis demonstrated that the CuMoO4sensor exhibited a linear increase in current response with increasing concentrations of paracetamol. This linear relationship indicates that CuMoO₄ is capable of detecting paracetamol effectively, with a strong and quantifiable signal response. Conclusion The CuMoO4nanomaterial was successfully synthesized using a simple precipitation method and was characterized by its rock-like morphology and crystalline structure. Electrochemical testing using DPV showed that CuMoO4has excellent sensing capabilities for detecting paracetamol, with a clear and linear current response. These findings suggest that CuMoO4is a promising electrochemical sensing material for drug detection, potentially offering a reliable and efficient method for monitoring paracetamol and possibly other pharmaceuticals in various settings.

Characterization of Acid Hydrolyzed Taro Boloso-I (Colocasia esculenta Cultivar) Starch as a Diluent in Direct Compression of Tablets.

Corn, wheat, rice, potato, and cassava starches have been widely used as pharmaceutical excipients. However, the search for cost-effective local starch alternatives is necessary due to the availability and usage constraints. In Ethiopia, various plant species, including Taro Boloso-I, have been explored as potential sources of pharmaceutical starch. It is a variety of Colocasia esculenta with a high tuber yield and high starch content. However, the native starch requires modifications to enhance its functionality. Therefore, this study aimed to improve the native starch through acid modification and evaluate its performance as a direct compressible tablet excipient. The native starch was treated with a 6% w/v HCl solution for 192 hours, resulting in acid-modified Taro Boloso-I starch, which was then evaluated for suitability for direct compression. XRD patterns of both the native and modified starch showed characteristic A-type crystals, with significantly higher relative crystallinity observed in the latter. Additionally, the acid-modified starch exhibited a lower moisture content and improved flow properties. The compaction study also demonstrated its improved compactibility (tensile strength: 16.82 kg/cm2), surpassing both the native starch (13.17) and Starch 1500® (11.2). The modified starch also showed a lower lubricant sensitivity compared to the native starch and Starch 1500®. Furthermore, paracetamol tablets made with the modified starch exhibited higher mechanical strength and lower friability in all paracetamol concentrations. It incorporated up to 40% paracetamol while maintaining acceptable tablet characteristics, whereas the native starch and Starch 1500® were limited to 30% (w/w). Based on these findings, the modified starch showed promise as an alternative direct compressible excipient in tablet manufacturing.

INVESTIGATING THE EFFECT OF HYDROGEN PEROXIDE ON PHOTOCATALYTIC DEGRADATION OF COMMERCIAL PARACETAMOL USING TiO2

The role of hydrogen peroxide on paracetamol degradation was investigated. Photocatalysis system contains UV radiation and commercial titania (TiO2 ) as catalyst. The parameters studied for optimal photocatalysis conditions were catalyst dose (0.05 - 0.2 g), initial concentration of paracetamol (5 - 20 mg L-1), and irradiation times (0 - 210 min). Optimal condition obtained by determining the changes of paracetamol concentration converted to be degradation percentage. The influence of hydrogen peroxide concentrations (1 % - 7 %) on photocatalysis TiO2 system was studied. The highest paracetamol degradation was obtained at addition of 3 %. It gives positive effect on degradation process. Thus, hybrid process (UV / TiO2 / H2O2 ) is more effective in comparison to the process UV/ TiO2 and UV/H2O2. Paracetamol (5 mg L-1) was degraded about 90.80 % using 0.1 g TiO2 , 3 % H2O2 addition for 180 min. According to the GC-MS analysis results, paracetamol degradation forms new less toxic by-products. The hybrid process is an alternative technique for degradation of wastewater containing paracetamol.

Photocatalytic degradation of paracetamol on immobilized TiO2 in a low-tech reactor by solar light for water treatment

Photocatalytic water treatment is an appealing concept to mineralize organic contaminants in contaminated water. In this study, the UV-resistant drug paracetamol (PCT) in aqueous solution is degraded by using a solar irradiated loop-reactor equipped with a TiO2 (P25) photocatalyst. The catalyst powder was dispersed in a geopolymer surface coating applied to aluminum-U-profiles connected by filament-printed polymer elements. Different assays with variations in initial PCT concentration were performed under natural solar radiation to determine the degradation kinetics of the PCT and correlate it to applied solar radiation energy density. Depending on experimental conditions, degradation efficiencies of 37.0–75.1 % were achieved within 3 h. Control samples without catalyst show no degradation. No degradation of the catalyst activity was observed within 42 h of operation time. The study shows the feasibility of this simple and scalable reactor design and coating technology for water purification under off-grid conditions provided sufficient solar radiation is available.