RESUMEN
Urine has an intricate composition with high concentrations of organic compounds like urea, creatinine, and uric acid. Urine poses a formidable challenge for advanced effluent treatment processes following urine diversion strategies. Urine matrix complexity is heightened when dealing with pharmaceutical residues like acetaminophen (ACT) and metabolized pharmaceuticals. This work explores ACT degradation in synthetic, fresh real, and hydrolyzed real urines using electrochemical oxidation with a dimensional stable anode (DSA). Analyzing drug concentration (2.5 - 40 mg L-1) over 180 min at various current densities in fresh synthetic effluent revealed a noteworthy 75% removal at 48 mA cm-2. ACT degradation kinetics and that of the other organic components followed a pseudo-first-order reaction. Uric acid degradation competed with ACT degradation, whereas urea and creatinine possessed higher oxidation resistance. Fresh real urine presented the most challenging scenario for the electrochemical process. Whereas, hydrolyzed real urine achieved higher ACT removal than fresh synthetic urine. Carboxylic acids like acetic, tartaric, maleic, and oxalic were detected as main by-products. Inorganic ionic species nitrate, nitrite, and ammonium ions were released to the medium from N-containing organic compounds. These findings underscore the importance of considering urine composition complexities and provide significant advancements in strategies for efficiently addressing trace pharmaceutical contamination.
Asunto(s)
Acetaminofén , Acetaminofén/química , Acetaminofén/orina , Humanos , Técnicas Electroquímicas , Orina/química , Oxidación-Reducción , CinéticaRESUMEN
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and paracetamol can be administered off-label to cattle. Since the use of these veterinary medicines in cattle may pose a public health risk after meat consumption, it is important to translate measured concentrations in urine and tissues into concentrations in meat for human consumption. A generic physiologically-based kinetic (PBK) model for cattle can enable this translation. In this work, a beef cattle PBK model was applied to calculate the relationships between concentrations in different bovine tissues and those were compared to measured concentrations in different matrices. Sixty-seven kidney samples, the corresponding urine and meat samples, and available 19 serum samples were analysed. Overall, 70% of the PBK model predictions are within a 2-fold factor and relationships for kidney/meat, urine/meat, and plasma/meat ratios were established. The conversions of measured kidney concentrations into meat concentrations were mostly within a factor two, while those based on plasma and urine were underpredicted. Based on these ratios, plasma and urine could be used as an appropriate surrogate matrix for a fast, simple in vivo sample screening test under field conditions, such as in local farms and slaughterhouses, to predict a maximum residue level exceedance in meat, reducing the number of test samples.
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Acetaminofén , Antiinflamatorios no Esteroideos , Animales , Bovinos , Acetaminofén/orina , Acetaminofén/sangre , Acetaminofén/farmacocinética , Antiinflamatorios no Esteroideos/sangre , Antiinflamatorios no Esteroideos/análisis , Riñón/efectos de los fármacos , Riñón/química , Riñón/metabolismo , Modelos Biológicos , Carne/análisis , Distribución Tisular , Carne Roja/análisisRESUMEN
Amlodipine (AM) is a long active calcium channel blocker used to relax blood vessels by preventing calcium ion transport into the vascular walls and its supporting molecules acetaminophen (AP) and ascorbic acid (AA) are recommended for hypertension control and prevention. Considering their therapeutic importance and potential side effects due to over dosage, we have fabricated a sensor for individual and simultaneous determination of AA, AP, and AM in pharmaceuticals and human urine using novel Zn-doped Ca2CuO3 nanoparticles modified glassy carbon electrode (GCE). Optimally doped Ca2CuO3 (2.5 wt% Zn at Cu site) enhanced the detection of target molecules over much wider concentration ranges of 50 to 3130 µM for AA, 0.25 to 417 µM for AP, and 0.8 to 354 µM for AM with the corresponding lowest detection limits of 14 µM, 0.05 µM, and 0.07 µM, respectively. Furthermore, the Zn-Ca2CuO3/GCE exhibited excellent selectivity and high sensitivity even in the presence of several potential interfering agents. The usefulness of the developed electrode was tested using an amlodipine besylate tablet and urine samples of seven hypertension patients under medication. The results confirmed the presence of a significant amount of AP and AM in six patients' urine samples indicating that the personalized medication is essential and the quantum of medication need to be fixed by knowing the excess medicines excreted through urine. Thus, the Zn-Ca2CuO3/GCE with a high recovery percentage and good sensitivity shall be useful in the pharmaceutical and biomedical sectors.
Asunto(s)
Acetaminofén , Amlodipino , Ácido Ascórbico , Cobre , Electrodos , Hipertensión , Zinc , Amlodipino/orina , Amlodipino/análisis , Humanos , Ácido Ascórbico/orina , Cobre/química , Acetaminofén/orina , Zinc/química , Zinc/orina , Hipertensión/tratamiento farmacológico , Hipertensión/orina , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Límite de Detección , Nanopartículas del Metal/química , Nanopartículas/química , Carbono/químicaRESUMEN
BACKGROUND: Metabolites present in human urine can be influenced by individual physiological parameters (e.g., body mass index [BMI], age, and sex). Observation of altered metabolites concentrations could provide insight into underlying disease pathology, disease prognosis and diagnosis, and facilitate discovery of novel biomarkers. METHODS: Quantitative metabolomics analysis in the urine of 183 healthy individuals was performed based on high-resolution liquid chromatography-mass spectrometry (LC-MS). Coefficients of variation were obtained for 109 urine metabolites of all the 183 human healthy subjects. RESULTS: Three urine metabolites (such as dehydroepiandrosterone sulfate, acetaminophen glucuronide, and p-anisic acid) with CV183 > 0.3, for which metabolomics studies have been scarce, are considered highly variable here. We identified 30 age-related metabolites, 18 BMI-related metabolites, and 42 sex-related metabolites. Among the identified metabolites, three metabolites were found to be associated with all three physiological parameters (age, BMI, and sex), which included dehydroepiandrosterone sulfate, 3-methylcrotonylglycine and N-acetyl-aspartic acid. Pearson's coefficients demonstrated that some age-, BMI-, and sex-related compounds are strongly correlated, suggesting that age, BMI, and sex could affect them concomitantly. CONCLUSION: Metabolic differences between distinct physiological statuses were found to be related to several metabolic pathways (such as the caffeine metabolism, the amino acid metabolism, and the carbohydrate metabolism), and these findings may be key for the discovery of new diagnostics and treatments as well as new understandings on the mechanisms of some related diseases.
Asunto(s)
Acetaminofén/análogos & derivados , Variación Biológica Poblacional , Sulfato de Deshidroepiandrosterona/orina , Acetaminofén/orina , Adulto , Biomarcadores/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Urinálisis/métodos , Urinálisis/normasRESUMEN
Sulfotransferase enzymes (SULT) catalyse sulfoconjugation of drugs, as well as endogenous mediators, gut microbiota metabolites and environmental xenobiotics. To address the limited evidence on sulfonation activity from clinical research, we developed a clinical metabolic phenotyping method using paracetamol as a probe substrate. Our aim was to estimate sulfonation capability of phenolic compounds and study its intraindividual variability in man. A total of 36 healthy adult volunteers (12 men, 12 women and 12 women on oral contraceptives) received paracetamol in a 1 g-tablet formulation on three separate occasions. Paracetamol and its metabolites were measured in plasma and spot urine samples using liquid chromatography-high resolution mass spectrometry. A metabolic ratio (Paracetamol Sulfonation Index-PSI) was used to estimate phenol SULT activity. PSI showed low intraindividual variability, with a good correlation between values in plasma and spot urine samples. Urinary PSI was independent of factors not related to SULT activity, such as urine pH or eGFR. Gender and oral contraceptive intake had no impact on PSI. Our SULT phenotyping method is a simple non-invasive procedure requiring urine spot samples, using the safe and convenient drug paracetamol as a probe substrate, and with low intraindividual coefficient of variation. Although it will not give us mechanistic information, it will provide us an empirical measure of an individual's sulfonator status. To the best of our knowledge, our method provides the first standardised in vivo empirical measure of an individual's phenol sulfonation capability and of its intraindividual variability. EUDRA-CT 2016-001395-29, NCT03182595 June 9, 2017.
Asunto(s)
Acetaminofén/metabolismo , Fenol/metabolismo , Sulfotransferasas/metabolismo , Acetaminofén/sangre , Acetaminofén/orina , Adulto , Cromatografía Líquida de Alta Presión , Femenino , Humanos , MasculinoRESUMEN
PURPOSE: Acetaminophen (APAP) has hepatotoxic potential when overdosed. Recent studies have reported serum alanine aminotransferase (ALT) elevations that resolve spontaneously with continued use of the drug, referred to as adaptation, in several individuals receiving therapeutic doses of APAP. However, the clinical significance of these ALT elevations remains unclear. This study was performed to investigate the incidence and characteristics of hepatic adaptation to therapeutic doses of APAP in healthy individuals. METHODS: In a randomized, single-blind, placebo-controlled study, 242 healthy Japanese individuals were enrolled. Each person received 3 g/d of APAP (n = 202) or placebo (n = 40) for 28 days. All study participants underwent analysis of genetic polymorphisms of CYP2E1 and UGT1A1; measurements of plasma APAP concentration and urine metabolites (glucuronide, sulfate, cysteine, and mercapturate); liver function monitoring, including ALT, microRNA-122, and high-mobility group box 1. Individuals with ALT levels remaining below the upper limit of normal (ULN; 40 U/L) during the study period were defined as tolerant and those with ALT elevations above the ULN as susceptible. Susceptible individuals who developed ALT elevations exceeding 2 × ULN discontinued use of the study drug for tolerability consideration. Susceptible individuals who had ALT elevations that decreased toward the ULN spontaneously with continued use of the study drug were classified as adaptation. FINDINGS: In the APAP group, 129 individuals (66%) were classified as tolerant and 65 (34%) as susceptible. Among 65 susceptible individuals, 12 (18%) discontinued use of APAP because of ALT elevations (>2 × ULN), whereas 53 (82%) completed 28-day APAP dosing. Thirty of 65 susceptible individuals (46%) had adaptation within 28 days. In the placebo group, no individuals was withdrawn from the study because of elevated ALT levels, 33 individuals (89%) were classified as tolerant, and 4 (11%) were classified as susceptible. None had clinical signs of liver injury. ALT level correlated significantly with microRNA-122 but not with high-mobility group box 1. No association was found between plasma APAP concentrations and ALT levels. Urinary excretion of APAP mercapturate was higher in susceptible than in tolerant individuals (P = 0.018, Wilcoxon or Kruskal-Wallis test). The frequency of homozygotes and compound heterozygotes for UGT1A1∗28 and UGT1A1∗6 (∗28/∗28, ∗6/∗6, and ∗6/∗28) was higher in susceptible than in tolerant individuals (13.9% vs 3.9%; P = 0.011, χ2 test). IMPLICATIONS: These findings indicate that in healthy individuals, APAP at a therapeutic dose can cause transient and self-limiting ALT elevation, reflecting subclinical hepatocellular damage, and these ALT elevations may be associated with the disposition of APAP metabolites and genetic factors. UMIN-CTR identifier: UMIN000019607.
Asunto(s)
Acetaminofén/administración & dosificación , Alanina Transaminasa/sangre , Analgésicos no Narcóticos/administración & dosificación , Acetaminofén/sangre , Acetaminofén/farmacocinética , Acetaminofén/orina , Adulto , Analgésicos no Narcóticos/sangre , Analgésicos no Narcóticos/farmacocinética , Analgésicos no Narcóticos/orina , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/orina , Citocromo P-450 CYP2E1/genética , Tolerancia a Medicamentos/genética , Femenino , Glucuronosiltransferasa/genética , Proteína HMGB1 , Voluntarios Sanos , Humanos , Hígado/metabolismo , Masculino , MicroARNs , Método Simple Ciego , Adulto JovenRESUMEN
OBJECTIVES: To study the effects of running with/without the use of pain killers on urinary neutrophil gelatinase-associated lipocalin (uNGAL) and other parameters of kidney function in recreational runners. METHODS: Participants of the 10- and 21.1-km Weir Venloop race were enrolled and their urine samples collected before and after the run. Urine dipstick and other conventional tests used to assess kidney function were performed. The presence of ibuprofen, diclofenac, naproxen, and/or paracetamol was assessed by LC-MS/MS. uNGAL was measured with a two-step chemiluminescent immunoassay. RESULTS: NSAIDs/analgesics were detected in urine of 5 (14.4%) 10-km runners and 13 (28.9%) 21.1-km runners. Only half-marathon participants showed significant increases in uNGAL (pre: 11.7 [7.1-34.3] ng/mL; post: 33.4 [17.4-50.4] ng/mL; P = .0038). There was a significant effect of NSAID/analgesic use on uNGAL increase (F2, 76 = 4.210, P = .004). Post hoc tests revealed that uNGAL increased significantly in runners who tested positive for ibuprofen/naproxen compared to runners who did not use any medications (P = .045) or those who tested positive for paracetamol (P = .033). Running distance had a significant influence on the increase in uNGAL (F1, 53 = 4.741, P < .05), specific gravity (F1, 60 = 9.231, P < .01), urinary creatinine (F1, 61 = 10.574, P < .01), albumin (F1, 59 = 4.888, P < .05), and development of hematuria (χ2 (4) = 18.44, P = .001). CONCLUSIONS: Running distance and use of ibuprofen/naproxen were identified as risk factors for uNGAL increase in recreational runners.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Lipocalina 2/orina , Carrera/fisiología , Acetaminofén/farmacología , Acetaminofén/orina , Adulto , Análisis de Varianza , Antiinflamatorios no Esteroideos/orina , Diclofenaco/farmacología , Diclofenaco/orina , Femenino , Humanos , Ibuprofeno/farmacología , Ibuprofeno/orina , Riñón/fisiología , Mediciones Luminiscentes , Masculino , Persona de Mediana Edad , Naproxeno/farmacología , Naproxeno/orina , Método Simple CiegoRESUMEN
New multi-walled carbon nanotubes supported on Ti3C2-MXene and chitosan (chit) composite film-based electrochemical sensor for ifosfamide (IFO), acetaminophen (ACOP), domperidone (DOM), and sumatriptan (SUM) have been developed. Ti3C2-MXene was synthesized by a fluoride method. Structural and chemical characterizations suggested the successful preparation of Ti3C2-MXene with clearly seen layered morphology, defined 0 0 2 diffraction peak at 7.5° and complete absence of 1 0 4 plane at 39°. The electrochemical performance of the sensor was investigated by cyclic voltammetry and adsorptive stripping differential pulse voltammetry. The Ti3C2/MWCNT/Chit modified glassy carbon electrode exhibits enhanced electrocatalytic activities toward the oxidation of target analytes. Excellent conductivity, large surface area, and high catalytic properties of the Ti3C2-MXene showed synergistic effects with MWCNTs and helped in achieving low detection limits of targets with high selectivity and reproducibility. The assay allows determination of IFO, ACOP, DOM, and SUM in the concentration ranges 0.0011-1.0, 0.0042-7.1, 0.0046-7.3, and 0.0033-61 µM with low detection limits of 0.00031, 0.00028, 0.00034, and 0.00042 µM, respectively. The sensor was successfully applied for voltammetric screening of target analytes in urine and blood serum samples with recoveries > 95.21%. Schematic illustration of the synthesis of self-assembled MXene/MWCNT/chitosan nanocomposite is given and its application to the voltammetric determination of ifosfamide, acetaminophen, domperidone, and sumatriptan described. Graphical abstract.
Asunto(s)
Quitosano/química , Técnicas Electroquímicas/métodos , Nanocompuestos/química , Nanotubos de Carbono/química , Titanio/química , Acetaminofén/sangre , Acetaminofén/orina , Domperidona/sangre , Domperidona/orina , Humanos , Ifosfamida/sangre , Ifosfamida/orina , Límite de Detección , Reproducibilidad de los Resultados , Sumatriptán/sangre , Sumatriptán/orinaRESUMEN
Nickel-ferrite nanoparticles (NiFe2O4) were synthesized by a hydrothermal method. They were used to modify a carbon paste electrode (CPE) and to prepare an electrochemical sensor for simultaneous determination of rizatriptan benzoate (RZB) and acetaminophen (AC). The structure and morphology of the bare CPE and modified CPE were studied using field emission scanning electron microscopy, while the structural characterization of NiFe2O4 was performed via X-ray diffraction. In the potential range 0.2-1.2 V, AC and RZB were detected at potentials of 0.5 V and 0.88 V (vs. Ag/AgCl saturated KCl 3 M), respectively. Both calibration plots are linear in the 1 to 90 µM concentration range. The limits of detection (at 3σ) of AC and RZB are 0.49 and 0.44 µM, respectively. The performance of the modified CPE was evaluated by quantifying the two drugs in spiked urine and in tablets. Graphical abstract The modified electrode consist of Nickel-ferrite and graphite by differential pulse voltammetry methods are schematically presented for simultaneous detection of acetaminophen (a painkiller drug) and rizatriptan benzoate (an antimigraine drug) in human urine and tablet samples.
Asunto(s)
Acetaminofén/orina , Técnicas Electroquímicas/métodos , Compuestos Férricos/química , Nanopartículas del Metal/química , Níquel/química , Triazoles/orina , Triptaminas/orina , Acetaminofén/química , Carbono/química , Técnicas Electroquímicas/instrumentación , Electrodos , Humanos , Límite de Detección , Oxidación-Reducción , Comprimidos/análisis , Triazoles/química , Triptaminas/químicaRESUMEN
The present study is the first report of in-situ growth and application of nanorods-flower like Co3O4 nanosorbent coated on the anodized aluminum substrate for thin film microextraction (TFME) approach. The flower like Co3O4 was successfully fabricated by conversion of Co-Al layered double hydroxide (LDH) precursor to Co3O4 using the simple calcinations process. The cheap and available aluminum foil was electrochemically anodized and used as a porous substrate. Response surface methodology (RSM) was explored for optimization step. Different acidic drugs, including: paracetamol, ibuprofen, aspirin and diclofenac were extracted from biological fluids in order to investigate the capability of the prepared sorbent. The extracted analytes were then analyzed using high performance liquid chromatography-ultraviolet detection (HPLC-UV). Under the optimized conditions, the limits of detection were between 0.2 and 1.7 µg L-1 in different selected matrices. The obtained limits of quantification were also calculated to be between 0.8 and 5.1 µg L-1 in the selected matrices. In addition the enrichment factors were also in the range of 105-169. Batch-to-batch reproducibility at 100 µg L-1 concentration level was also evaluated to be lower than 5.2% (n = 3). Finally, the method was successfully used for analysis of these compounds in the biological fluids.
Asunto(s)
Ácidos/orina , Aluminio/química , Cobalto/química , Nanotubos/química , Óxidos/química , Acetaminofén/orina , Adsorción , Adulto , Aspirina/orina , Cromatografía Líquida de Alta Presión , Diclofenaco/orina , Técnicas Electroquímicas , Electrodos , Femenino , Humanos , Hidróxidos/química , Ibuprofeno/orina , Límite de Detección , Masculino , Reproducibilidad de los Resultados , Microextracción en Fase Sólida , Propiedades de SuperficieRESUMEN
An electrochemical sensing platform based upon screen-printing electrodes (SPEs) modified with nanostructured lanthanide metal oxides facilitate the detection of the widely misused drugs acetaminophen (ACP) and tramadol (TRA). Among the metal oxides examined, Yb2O3 nanoplates (NPs) were found to give rise to an optimal electrochemical response. The electroanalysis of ACP and TRA individually, and within mixtures, was performed using cyclic and differential pulse voltammetry. The ACP and TRA exhibited non-overlapping voltammetric signals at voltages of +0.30 and + 0.67 V (vs. Ag/AgCl; pH 9) using Yb2O3-SPEs. Pharmaceutical dosage forms and spiked human fluids were analyzed in wide linear concentration ranges of 0.25-654 and 0.50-115 µmol.L-1 with limits of detection (LOD) of 55 and 87 nmol.L-1 for ACP and TRA, respectively. The Yb2O3-SPEs offer a sensitive and chemically stable enzyme-free electrochemical platform for ACP and TRA assay. Graphical abstractSchematic presentation of one-shot electrochemical analysis of misused drugs, tramadol (TRA) and acetaminophen (ACP) by utilizing ytterbium oxide nanoplates modified screen-printed electrodes (Yb2O3-SPEs). The Yb2O3-SPEs showed interesting responses for ACP and TRA within pharmaceutical formulations and human fluids.
Asunto(s)
Acetaminofén/análisis , Analgésicos/análisis , Nanoestructuras/química , Óxidos/química , Tramadol/análisis , Iterbio/química , Acetaminofén/sangre , Acetaminofén/orina , Analgésicos/sangre , Analgésicos/orina , Técnicas Electroquímicas/instrumentación , Técnicas Electroquímicas/métodos , Electrodos , Humanos , Límite de Detección , Reproducibilidad de los Resultados , Tramadol/sangre , Tramadol/orinaRESUMEN
Background: Acetaminophen is a common pharmaceutical ingestion reported to US poison centers. In overdose, toxic metabolites are known to cause hepato- and nephrotoxicity. While G6PD deficiency may be a risk factor for methemoglobin production in the setting of acetaminophen overdose, it is rarely reported in patients who do not have this condition.Methods: We present two cases of methemoglobinemia following massive acetaminophen ingestion with no known history of G6PD deficiency or other substances known to induce methemoglobinemia. The two cases had peak methemoglobin measurements of 32% and 12% respectively, and both were treated with methylene blue.Discussion: A number of mechanisms may be involved in production of methemoglobin in the setting of massive acetaminophen ingestion including NAPQI-induced oxidation, depletion of glutathione stores, and production of oxidant-metabolites including paraaminophenol. While it is unlikely that the majority of acetaminophen overdoses result in any clinically significant methemoglobinemia, massive acetaminophen overdose may be complicated by development of methemoglobinemia.Conclusion: Physicians should be aware of the possibility that massive acetaminophen ingestion may be complicated by methemoglobinemia in rare instances. Further studies should aim to characterize the metabolic pathways leading to possible methemoglobinemia in humans after large acetaminophen ingestions.
Asunto(s)
Acetaminofén/envenenamiento , Sobredosis de Droga/etiología , Metahemoglobinemia/inducido químicamente , Acetaminofén/sangre , Acetaminofén/orina , Sobredosis de Droga/sangre , Sobredosis de Droga/terapia , Sobredosis de Droga/orina , Resultado Fatal , Femenino , Humanos , Masculino , Metahemoglobina/análisis , Metahemoglobinemia/sangre , Metahemoglobinemia/terapia , Metahemoglobinemia/orina , Azul de Metileno/uso terapéutico , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
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 6â¯×â¯10-8 to 5â¯×â¯10-5â¯molâ¯L-1 and 5â¯×â¯10-5 to 2â¯×â¯10-4â¯molâ¯L-1, with a detection limit based on the lower linear range of 1.73â¯×â¯10-8â¯molâ¯L-1(S/Nâ¯=â¯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%.
Asunto(s)
Acetaminofén/análisis , Analgésicos no Narcóticos/análisis , Técnicas Electroquímicas/métodos , Imanes/química , Impresión Molecular/métodos , Polímeros/química , Acetaminofén/sangre , Acetaminofén/orina , Analgésicos no Narcóticos/sangre , Analgésicos no Narcóticos/orina , Técnicas Biosensibles/métodos , Humanos , Límite de Detección , Membranas Artificiales , ComprimidosRESUMEN
A comparative study was carried out on the electrochemical behavior of three carbonized zeolitic imidazolate frameworks (ZIFs) synthesized through solvothermal pyrolysis. An electrochemical sensor for acetaminophen (ACT) was subsequently developed. The sensor was made by coating the glassy carbon electrode (GCE) with cobalt-nitrogen co-doped carbon nanotube hollow polyhedron (Co-NCNHP), which was prepared from core shell ZIF-8@ZIF-67, before electrodeposition of gold nanoparticles. Due to the high specific surface area, good electrical conductivity and stability of both Co-NCNHP and the gold nanoparticles, the resultant sensor displayed excellent electrocatalytic activity towards ACT with the catalytic rate constant Kcat of 4.9 × 105 M-1 s-1, diffusion coefficient D of 1.8 × 10-6 cm2 s-1, high sensitivity of 1.75 µA µM-1 cm-2, and best at a working voltage of 0.35 V (vs. Ag/AgCl). Benefitting from the synergistic effect of both Co-NCNHP and gold nanoparticles, the modified GCE had a linear response in the 0.1 µM-250 µM ACT and detection limit of 0.05 µM (at S/N = 3). The sensor was successfully applied to quantify ACT in tablets and spiked urine samples with recoveries ranged between 96.0% and 105.2%. Graphical abstractSchematic representation of cobalt-nitrogen co-doped carbon nanotube hollow polyhedrons (Co-NCNHP) exhibiting superior electrocatalytic activity to carbonized ZIF-8 and carbonized ZIF-67. Co-NCNHP were coupled to electrodeposition gold nanoparticles to modify glassy carbon electrode for improving acetaminophen (ACT) redox.
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Acetaminofén/análisis , Galvanoplastia , Oro/química , Imidazoles/química , Nanopartículas del Metal/química , Nanotubos de Carbono/química , Zeolitas/química , Acetaminofén/química , Acetaminofén/orina , Catálisis , Difusión , Electroquímica , Electrodos , Humanos , Concentración de Iones de Hidrógeno , Cinética , Límite de DetecciónRESUMEN
Lanthanum oxide nanomaterials were decorated with carbon black (CB) and grafted with a poly(acrylic acid) nanogel to obtain a composite material (CB-g-PAA/La2O3) for simultaneous determination of acetaminophen (AMP), naproxen (NPX), and theophylline (TPH). The nanogel was synthesized by in-situ free radical polymerization. The composite was dropped onto a glassy carbon electrode (GCE), and the modified GCE displays robust electrocatalytic activity towards AMP, NPX, and TPH, with voltammetric signals that are enhanced compared to a bare GCE. Features of merit for AMP, NPX, and TPH, respectively, include (a) peak potentials of 0.42, 0.85 and 0.12 V (vs. Ag/AgCl), (b) linear ranges from 0.05-887, 0.05-884, and 0.02-888 µM, and (c) detection limits of 20, 35, and 15 nM. The practical applicability of the CB-g-PAA/La2O3/GCE was illustrated by analyzing serum and urine samples. Graphical abstract Schematic presentation of simultaneous electrochemical sensing of acetaminophen (AMP), naproxen (NPX), and theophylline (TPH) in real sample analysis using poly(acrylic acid) nanogel covalently grafted onto a carbon black/La2O3 composite (CB-g-PAA/La2O3/GCE).
Asunto(s)
Acetaminofén/análisis , Resinas Acrílicas/química , Lantano/química , Nanogeles/química , Naproxeno/análisis , Óxidos/química , Hollín/química , Teofilina/análisis , Acetaminofén/sangre , Acetaminofén/orina , Electroquímica , Electrodos , Humanos , Modelos Moleculares , Conformación Molecular , Naproxeno/sangre , Naproxeno/orina , Polimerizacion , Teofilina/sangre , Teofilina/orinaRESUMEN
In this study, a capillary electrophoresis-tandem mass spectrometry method combining efficient separation and sensitive detection has been developed and validated, for the first time, to quantify acetaminophen and five of its metabolites in urine samples. Optimization of the method has led us to perform detection in positive ESI mode using MeOH-ammonium hydroxide (0.1%) (50:50, v/v) as sheath liquid. Moreover, optimal separation has been obtained in less than 9â¯min after anodic injection, using an ammonium acetate solution (40â¯mM, pH 10) as BGE. It was shown that the dilution solvent and the dilution factor to use for sample preparation are critical parameters to avoid peak splitting, to gain in sensitivity and then to obtain an effective analysis method. While a 200-fold factor dilution was shown to be suitable for quantitation of acetaminophen, acetaminophen mercapturate, acetaminophen sulfate and acetaminophen glucuronide, a 20-fold dilution was finally selected for methoxy-acetaminophen and 3-methylthioacetaminophen analysis, thus requiring two successive analyses to be carried out in order to quantify all metabolites. Hyphenation of CE with MS/MS versus UV permits to improve LOQ (10-20-fold factor with respect to previous works for acetaminophen, acetaminophen sulfate and acetaminophen glucuronide). Moreover, use of CE versus HPLC, permits to quantify two additional metabolites, i.e. 3-methylthio-acetaminophen and methoxy-acetaminophen. The method has been validated using the accuracy profile approach with a total error (accuracy) included in the ± 20% range. Thereby, the method allows the quantitation of acetaminophen and acetaminophen mercapturate in the range (0.1-1â¯mg mL-1), and of acetaminophen sulfate, methoxy-acetaminophen, acetaminophen glutathione and 3-methylthio-acetaminophen in the ranges (0.5-5â¯mg mL-1), (0.025-0.4â¯mg mL-1), (9.22-30â¯mg mL-1) and (0.073-0.4â¯mg mL-1), respectively. The method was finally applied to the analysis of urine samples of eighteen patients belonging to three different inclusion groups of the ongoing clinical trial, demonstrating that the method is suitable to highlight different metabolic profiles. This work will be subsequently extended to the analysis two hundred and seventy urine samples from patients included in a clinical trial dedicated to the study of acetaminophen metabolism changes after hepatic resection.
Asunto(s)
Acetaminofén/análogos & derivados , Acetaminofén/orina , Acetaminofén/metabolismo , Electroforesis Capilar/métodos , Humanos , Espectrometría de Masas en Tándem/métodosRESUMEN
The authors have modified a carbon paste electrode with Al2O3-supported palladium nanoparticles (PdNP@Al2O3) to obtain a sensor for simultaneous voltammetric determination of melatonin (MT), dopamine (DA) and acetaminophen (AC). The PdNP@Al2O3 was characterized by scanning electron microscopy and energy-dispersive X-ray spectra. The sensor can detect DA, AC, MT and their mixtures by giving distinct signals at working voltages of typically 236, 480 and 650 mV (vs. Ag/AgCl), respectively. Differential pulse voltammetric peak currents of DA, AC and MT increase linearly in the 50 nmol L-1 - 1.45 mmol L-1, 40 nmol L-1 -1.4 mmol L-1, and 6.0 nmol L-1 - 1.4 mmol L-1 concentration ranges. The limits of detection are 36.5 nmol L-1 for DA, 36.5 nmol L-1 for AC, and 21.6 nmol L-1 for MT. The sensor was successfully used to detect the analytes in (spiked) human serum and drug samples. Graphical abstract Schematic presentation of Al2O3-supported palladium nanoparticles (PdNP@Al2O3) for modification of a carbon paste electrode (CPE) to develop a voltammetric sensor for the simultaneous determination of dopamine (DA), acetaminophen (AC) and melatonin (MT).
Asunto(s)
Acetaminofén/análisis , Óxido de Aluminio/química , Dopamina/análisis , Melatonina/análisis , Nanopartículas del Metal/química , Paladio/química , Acetaminofén/sangre , Acetaminofén/química , Acetaminofén/orina , Carbono/química , Dopamina/sangre , Dopamina/química , Dopamina/orina , Técnicas Electroquímicas , Electrodos , Humanos , Melatonina/sangre , Melatonina/química , Melatonina/orinaRESUMEN
An amperometric biosensor compatible with a flow injection analysis (FIA) for highly selective determination of acetaminophen (APAP) in a sample of human urine was developed. This biosensor is also suitable for use in the routine pharmaceutical practice. To prove this statement, two different commercially available pharmaceutical formulations were analyzed. This nano-(bio)electroanalytical device was made from a commercially available screen-printed carbon electrode covered by a thin layer of non-functionalized graphene (NFG) as amperometric transducer. A biorecognition layer was prepared from mushroom (Agaricus bisporus) tyrosinase (EC 1.14.18.1) cross-linked using glutaraldehyde, where resulting aggregates were covered by Nafion®, a known ion exchange membrane. Owing to the use of tyrosinase and presence of NFG, the developed analytical instrument is able to measure even at potentials of 0 V. Linear ranges differ according to choice of detection potential, namely up to 130 µmol L-1 at 0 V, up to 90 µmol L-1 at -0.1 V, and up to 70 µmol L-1 at -0.15 V. The first mentioned linear range is described by the equation Ip [µA] = 0.236 - 0.1984c [µmol L-1] and correlation coefficient r = 0.9987; this equation was used to quantify the content of APAP in each sample. The limit of detection of APAP was estimated to be 1.1 µmol L-1. A recovery of 96.8% (c = 25 µmol L-1, n = 5 measurements) was calculated. The obtained results show that FIA is a very selective method for APAP determination, being comparable to the chosen reference method of reversed-phase high-performance liquid chromatography.
Asunto(s)
Acetaminofén/orina , Agaricus/enzimología , Analgésicos no Narcóticos/orina , Técnicas Biosensibles/métodos , Análisis de Inyección de Flujo/métodos , Monofenol Monooxigenasa/química , Técnicas Biosensibles/instrumentación , Diseño de Equipo , Análisis de Inyección de Flujo/instrumentación , Humanos , Límite de Detección , Urinálisis/instrumentación , Urinálisis/métodosAsunto(s)
Analgésicos Opioides/uso terapéutico , Dolor/tratamiento farmacológico , Acetaminofén/metabolismo , Acetaminofén/uso terapéutico , Acetaminofén/orina , Analgésicos Opioides/orina , Lesiones Traumáticas del Encéfalo/patología , Cromatografía Líquida de Alta Presión , Codeína/metabolismo , Codeína/uso terapéutico , Codeína/orina , Femenino , Humanos , Hidrocodona/orina , Inmunoensayo , Espectrometría de Masas , Marihuana Medicinal/uso terapéutico , Persona de Mediana EdadRESUMEN
This research advances the knowledge of the pharmaceutical removal interactions by biochar in synthetic and real urine through the use of reference adsorbents and adsorbate probes. Earlier work has combined biochar and urine for pharmaceutical removal, however, the interactions that influence adsorption are unknown. In this study, bamboo biochar and softwood biochar were chosen as the representative materials and the model pharmaceuticals were naproxen and paracetamol. To further investigate the physical-chemical interactions, two nonpolar adsorbates, para-xylene and dimethylnaphthalene, were tested. Graphite and anion exchange resin, were used to isolate van der Waals and electrostatic interactions, respectively. Experimental kinetic and equilibrium data were fit to multiple adsorption models where the pseudo-second order and Freundlich exhibited the best fit, respectively. The Freundlich and Langmuir parameters had similar trends showing that softwood had the highest adsorption capacity. The model parameters indicated higher selectivity for nonpolar para-xylene and dimethylnaphthalene by graphite and polar paracetamol and naproxen by softwood biochar. The decreasing trend of importance of key interactions for pharmaceutical sorption to biochar are: van der Waalsâ¯>â¯hydrogen bondingâ¯>â¯electrostatic interactions. No statistically significant difference was found between urine age (fresh vs. hydrolyzed) and pharmaceutical removal; however, the urine matrix (synthetic vs. synthetic with metabolites vs. real urine) did show a statistically significant difference on pharmaceutical removal where synthetic urine had comparatively greater adsorption. As constituents (i.e., metabolites) were added to urine matrices, reduced adsorption of pharmaceuticals was observed, indicating that adsorption processes should be tested in real urine for accuracy.