RESUMEN
Here, an electrokinetic extraction (EkE) syringe is presented allowing for on-line electrokinetic removal of serum proteins before ESI-MS. The proposed concept is demonstrated by the determination of pharmaceuticals from human serum within minutes, with sample preparation limited to a 5× dilution of the sample in the background electrolyte (BGE) and application of voltage, both of which can be performed in-syringe. Signal enhancements of 3.6-32 fold relative to direct infusion of diluted serum and up to 10.8 fold enhancement, were obtained for basic and acidic pharmaceuticals, respectively. Linear correlations for the basic drugs by EkE-ESI-MS/MS were achieved, covering the necessary clinical range with LOQs of 5.3, 7.8, 6.1, and 17.8â ng mL-1 for clomipramine, chlorphenamine, pindolol, and atenolol, respectively. For the acidic drugs, the EkE-ESI-MS LOQs were 3.1â µg mL-1 and 2.9â µg mL-1 for naproxen and paracetamol, respectively. The EkE-ESI-MS and EkE-ESI-MS/MS methods showed good accuracy (%found of 81 % to 120 %), precision (≤20 %), and linearity (r>0.997) for all the studied drugs in spiked serum samples.
Asunto(s)
Proteínas Sanguíneas/aislamiento & purificación , Jeringas , Acetaminofén/sangre , Atenolol/sangre , Proteínas Sanguíneas/química , Clorfeniramina/sangre , Clomipramina/sangre , Humanos , Cinética , Naproxeno/sangre , Pindolol/sangre , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Prediction of human pharmacokinetics is important in the preclinical stage. Values for total clearance of compounds from plasma should be one of the most important pharmacokinetic parameters for predictions. Although several physiological and empirical methods including single-species allometry for prediction of values for human clearance of compounds using humanized-liver mice have been reported, further improvement of prediction accuracies would be still expected. To optimize these approaches, we proposed methods for unbound intrinsic clearance in virtually 100% humanized-liver mouse by incorporating unbound plasma fractions of compounds in differently humanized-liver mice. Comparisons of prediction accuracies of values for human clearance of 15 model compounds were performed among our current physiological and previously reported models and single-species allometry using humanized-liver mice. Incorporation of the actual unbound plasma fractions of compounds and correction of residual mice hepatocyte in humanized-liver mice showed comparable prediction accuracy to that by single-species allometry. After exclusion of 3 compounds with large species differences in values of clearance and unbound plasma fractions between mice and humans out of 15 compounds, prediction accuracies were improved in the methods investigated. The previously and present reported physiological methods could show the good prediction accuracy of values for clearance of drugs from plasma.
Asunto(s)
Hígado/metabolismo , Preparaciones Farmacéuticas/sangre , Preparaciones Farmacéuticas/metabolismo , Acetamidas/sangre , Acetamidas/farmacocinética , Albuterol/sangre , Albuterol/farmacocinética , Animales , Carbamatos/sangre , Carbamatos/farmacocinética , Cromatografía Liquida , Diazepam/sangre , Diazepam/farmacocinética , Diclofenaco/sangre , Diclofenaco/farmacocinética , Digitoxina/sangre , Digitoxina/farmacocinética , Humanos , Itraconazol/sangre , Itraconazol/farmacocinética , Cetoprofeno/sangre , Cetoprofeno/farmacocinética , Hígado/química , Tasa de Depuración Metabólica , Ratones , Ratones Transgénicos , Naproxeno/sangre , Naproxeno/farmacocinética , Fenitoína/sangre , Fenitoína/farmacocinética , Piperidinas/sangre , Piperidinas/farmacocinética , Pravastatina/sangre , Pravastatina/farmacocinética , Pirimidinas/sangre , Pirimidinas/farmacocinética , Quinidina/sangre , Quinidina/farmacocinética , Espectrometría de Masas en Tándem , Telmisartán/sangre , Telmisartán/farmacocinética , Terfenadina/análogos & derivados , Terfenadina/sangre , Terfenadina/farmacocinética , Verapamilo/sangre , Verapamilo/farmacocinéticaRESUMEN
In the present work, NiFe layered double hydroxide (LDH)/Nylon 6 composite nanofibers were prepared by electrospinning method and used as a new sorbent for the extraction and measurement of non-steroidal anti-inflammatory drugs (naproxen, mefenamic acid, and diclofenac) in whole blood samples. The method is based on micro solid phase extraction (µSPE) by packed sorbent followed by HPLC-UV analysis. Effective parameters on the extraction efficiency were optimized using a central composite design (CCD). In order to characterize the sorbent, Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), field emission scanning electron microscopy (FESEM), energy dispersive X-ray analysis (EDX) and elemental mapping were applied. The method was fully validated based on linearity, limits of detection (LOD) and quantification (LOQ), precision, and recovery. Under the optimal conditions, LOD values were found to be 25 ng mL-1 for naproxen and diclofenac and 15 ng mL-1 for mefenamic acid. A seven-point calibration curve was obtained in the range of 75-2000 ng mL-1 for naproxen and diclofenac and 50-2000 for mefenamic acid. The method showed good linearity with coefficients of determination, r2>â¯0.9962, for the three drugs. In the entire analytical range, the relative standard deviations (RSD%) were less than 8.1%. Finally, the efficiency of the method was investigated for the analysis of the target analytes in human blood samples, and the recoveries were obtained in the range of 90.7-109.8%.
Asunto(s)
Antiinflamatorios no Esteroideos/sangre , Nanofibras/química , Microextracción en Fase Sólida/métodos , Antiinflamatorios no Esteroideos/aislamiento & purificación , Caprolactama/análogos & derivados , Cromatografía Líquida de Alta Presión , Diclofenaco/sangre , Diclofenaco/aislamiento & purificación , Humanos , Hidróxidos/química , Hierro , Límite de Detección , Ácido Mefenámico/sangre , Ácido Mefenámico/aislamiento & purificación , Naproxeno/sangre , Naproxeno/aislamiento & purificación , Níquel , PolímerosRESUMEN
Previous reports have warned about the influence of spinal cord injury (SCI) on the pharmacokinetics of various drugs. However, the role of SCI in the efficacy and safety of pharmacotherapy remains unknown. Thereby, our aim was to explore the role of SCI on pharmacokinetics and anti-inflammatory effect of naproxen in response to a local inflammatory challenge. Rats received a severe contusive SCI at T9 or sham injury. Pharmacokinetics of a single intravenous dose of naproxen (10 mg kg-1) was studied at days 1 and 15 post-surgery. For the anti-inflammatory assessment, carrageenan was subcutaneously injected in forelimb and hindlimb paws at the same post-surgery periods, and naproxen efficacy was evaluated measuring paw swelling. Plasma protein concentrations and body weight changes were also determined. Plasma naproxen levels and pharmacokinetic parameters were unchanged by acute injury, but subacute injury generated alterations in volume of distribution, clearance, and bioavailability, resulting in significantly reduced plasma naproxen concentrations, in the absence of changes in plasma proteins. Assessment of naproxen anti-inflammatory activity during the acute stage of injury could not be determined because of carrageenan failure to elicit swelling. During the subacute stage, naproxen anti-inflammatory effect on forelimbs (above injury) was similar to that observed in sham-injured animals, while it was almost absent in paralyzed hindlimbs. Under conditions of SCI and peripheral inflammation, pharmacokinetics and anti-inflammatory activity of naproxen vary according to post-injury timing and neurological status of the assessed region.
Asunto(s)
Antiinflamatorios no Esteroideos/sangre , Antiinflamatorios no Esteroideos/uso terapéutico , Naproxeno/sangre , Naproxeno/uso terapéutico , Traumatismos de la Médula Espinal/sangre , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Femenino , Mediadores de Inflamación/sangre , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Vértebras Torácicas/lesiones , Resultado del TratamientoRESUMEN
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
A quick, simple and efficient method for extraction, preconcentration, and determination of naproxen in water and plasma specimens with acceptable recovery by dispersive liquid-liquid microextraction based on solidified floating organic drop with spectrofluorimetry is presented. Various parameters affecting the extraction efficiency are optimized by the Central Composite Design. Moreover, under optimal conditions (120 µL 1-Undecanol with 1 mL Ethanol, pH = 3.5, 2 mL KCl 10% solution), the calibration curve was linear in the range 10.0-120.0 ng/mL. Finally, for naproxen, the detection limit was 2.4 ng/mL.
Asunto(s)
Microextracción en Fase Líquida/métodos , Naproxeno/análisis , Naproxeno/aislamiento & purificación , Espectrometría de Fluorescencia/métodos , Centrifugación , Límite de Detección , Naproxeno/sangre , Solventes/química , Factores de Tiempo , Agua/químicaRESUMEN
Based on a one-step combustion fabrication approach, a novel magnetic porous carbon (MPC) was fabricated using filter paper as porous carbon source and iron salts as magnetic precursors. The textural properties of the MPC were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectrometry (FT-IR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), vibration sample magnetometer (VSM) and nitrogen absorption-desorption isotherms. The as-prepared MPC possessed a high specific surface area, a microstructure comprised of mesopores and strong magnetic response. It was employed as a magnetic solid-phase extraction (MSPE) adsorbent for the determination of three non-steroidal anti-inflammatory drugs (NSAIDs) in environmental water and biological samples coupled with high performance liquid chromatography (HPLC). The main parameters affecting extraction efficiency were investigated in detail and a satisfactory performance was obtained under the optimal conditions. The calibration curves were linear over the concentration ranging from 1 to 1200⯵gâ¯L-1 for ketoprofen (KET) and 2-1200⯵gâ¯L-1 for naproxen (NAP) and diclofenac (DCF) with determination coefficients (R2) between 0.9995 and 0.9997. The limits of detection (LODs) were in the range of 0.2-0.4⯵gâ¯L-1. The intra- and inter-day relative standard deviations (RSDs) were less than 4.03% and 8.72%, respectively. The recoveries ranged from 84.67% to 113.73% with RSDs less than 7.76%. The satisfactory results confirmed the great potential of the novel MPC adsorbent for the extraction of NSAIDs from complex sample matrices.
Asunto(s)
Antiinflamatorios no Esteroideos/análisis , Carbono/química , Diclofenaco/análisis , Cetoprofeno/análisis , Naproxeno/análisis , Adsorción , Antiinflamatorios no Esteroideos/sangre , Antiinflamatorios no Esteroideos/orina , Diclofenaco/sangre , Diclofenaco/orina , Tecnología Química Verde/métodos , Cetoprofeno/sangre , Cetoprofeno/orina , Límite de Detección , Nanopartículas de Magnetita/química , Naproxeno/sangre , Naproxeno/orina , Porosidad , Ríos/química , Extracción en Fase Sólida/instrumentación , Extracción en Fase Sólida/métodos , Contaminantes Químicos del Agua/análisisRESUMEN
The blood brain barrier is a major obstacle to the entry of the majority of CNS-active agents. In the present research, the potential of magnetic polymeric micelles (MPMs) for brain-targeting of naproxen was evaluated. The MPMs were made of methoxy poly(ethyleneglycol)-poly (caprolactone) copolymer and super paramagnetic iron oxide nanoparticles (SPIONs). To investigate the impact of particle size on the in vivo biofate of nanoparticles, MPMs with two different sizes were prepared. The prepared magnetic polymeric micelles had diameters of 137⯱â¯3.5â¯nm (MPM137) and 242⯱â¯6.2â¯nm (MPM242) and their surface charges were about -6.5 andâ¯-â¯4.5â¯mV, respectively. Pharmacokinetic and biodistribution of nanoparticles were characterized in rats using an external magnet of 0.4 Tesla field strength located on the skull of anesthetized animals. Significant differences in volumes of central as well as peripheral compartments were observed between both MPM formulations and free naproxen solution. After 8â¯h of administration, the brain concentration of naproxen was shown to be higher in the case of MPM137 in comparison with MPM242 and free drug. The findings revealed that the polymeric magnetic micelles with diameters smaller than 150â¯nm could be initially considered as a promising carrier to improve therapeutic agent accumulation in the brain for the treatment of CNS diseases.
Asunto(s)
Encéfalo/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Magnetismo , Micelas , Naproxeno/farmacología , Naproxeno/farmacocinética , Polímeros/química , Animales , Liberación de Fármacos , Masculino , Nanopartículas/química , Nanopartículas/ultraestructura , Naproxeno/administración & dosificación , Naproxeno/sangre , Tamaño de la Partícula , Poliésteres/síntesis química , Poliésteres/química , Polietilenglicoles/síntesis química , Polietilenglicoles/química , Espectroscopía de Protones por Resonancia Magnética , Ratas Sprague-Dawley , Espectroscopía Infrarroja por Transformada de Fourier , Electricidad Estática , Factores de Tiempo , Distribución Tisular/efectos de los fármacosRESUMEN
Rapid, simple, and sensitive submicellar liquid chromatography with fluorescence detection was developed and validated to quantify naproxen in plasma and brain samples after oral administration of Naproxen formulations. The method used tramadol as an internal standard. Different submicellar mobile phases with organic phases ranging from 40 to 60% were studied to improve the native fluorescence of the Naproxen and decrease retention times. Separation was done in a Zorbax SB C8 column (250 × 4.6 mm, 5 µm) with a mobile phase containing acidic 0.007 M sodium dodecyl sulfate/acetonitrile (50:50, v/v) at a flow rate of 1 mL/min. Detection was performed with an excitation wavelength of 280 nm and emission of 310 nm and 360 nm for internal standard and Naproxen, respectively. The method was validated by International Conference of Harmonization standards. The method is specific, accurate, and precise (relative standard deviation <3%). Limits of detection and quantification were 0.08 and 0.25 µg/mL, respectively, for biological samples. This method was applied to analyze brain/plasma ratios in mice that had received oral administrations of Naproxen micellar formulations containing 10% w/w of sodium dodecyl sulfate, Cremophor RH 40, or Tween 80. The sodium dodecyl sulfate micelles were faster and more widely distributed in the mouse brains.
Asunto(s)
Antiinflamatorios/análisis , Química Encefálica , Cromatografía Liquida/métodos , Naproxeno/análisis , Plasma/química , Animales , Antiinflamatorios/sangre , Cromatografía Liquida/instrumentación , Fluorescencia , Masculino , Ratones , Ratones Endogámicos BALB C , Naproxeno/sangreRESUMEN
Naproxen (nap) is belonging to Non-steriodal anti-inflammatory drugs (NSAIDs) group of drugs that characterized by their free carboxylic group. The therapeutic activity of nap is usually accompanied by GI untoward side effects. Recently synthesized naproxen amides of some amino acid esters prodrugs to mask the free carboxylic group were reported. Those prodrugs showed a promising colorectal cancer chemopreventive activity. The current study aims to investigate the fate and hydrolysis of the prodrugs kinetically in different pH conditions, simulated gastric and intestinal fluids with pHs of 1.2, 5.5 and 7.4 in vitro at 37⯰C. The effect of enzymes on the hydrolysis of prodrugs was also studied through incubation of these prodrugs at 37⯰C in human plasma and rat liver homogenates. The pharmacokinetic parameters of selected prodrugs and the liberated nap were studied after oral and intraperitoneal administration in male wistar rats. The results showed the hydrolysis of naproxen amides of amino acid esters to nap through two steps first by degradation of the ester moiety to form the amide of nap with amino acid and the second was through the degradation of the amide link to liberate nap. The two reactions were followed and studied kinetically where K1 and K2 (rate constants of degradation) is reported. The hydrolysis of prodrugs was faster in liver homogenates than in plasma. The relative bioavailability of the liberated nap in vivo was higher in case of prodrug containing ethyl glycinate moiety than that occupied l-valine ethyl ester moiety. Each of nap. prodrugs containing ethyl glycinate and l-valine ethyl ester moieties appears promising in liberating nap, decreasing direct GI side effect and consequently their colorectal cancer chemopreventive activity.
Asunto(s)
Amidas/farmacocinética , Aminoácidos/farmacocinética , Anticarcinógenos/farmacocinética , Naproxeno/análogos & derivados , Naproxeno/farmacocinética , Profármacos/farmacocinética , Administración Oral , Amidas/administración & dosificación , Amidas/sangre , Amidas/química , Aminoácidos/administración & dosificación , Aminoácidos/sangre , Aminoácidos/química , Animales , Anticarcinógenos/administración & dosificación , Anticarcinógenos/sangre , Anticarcinógenos/química , Neoplasias Colorrectales/tratamiento farmacológico , Estabilidad de Medicamentos , Ésteres/administración & dosificación , Ésteres/sangre , Ésteres/química , Ésteres/farmacocinética , Humanos , Concentración de Iones de Hidrógeno , Hidrólisis , Inyecciones Intraperitoneales , Cinética , Hígado/metabolismo , Masculino , Naproxeno/administración & dosificación , Naproxeno/sangre , Profármacos/administración & dosificación , Profármacos/análisis , Profármacos/química , Ratas WistarRESUMEN
AIM: Volumetric absorptive microsampling (VAMS) is a recent technology available for sampling and analyzing low blood volume. The present work describes the utilization of VAMS for the quantitation of naproxen and ritonavir in human blood using a novel bead-based impact-assisted extraction (IAE) procedure. RESULTS: Sampling volume accuracy of the VAMS device was independent of the blood hematocrit (HCT) level, however analyte recovery decreased with increasing HCT when extracted using ultrasonication. In contrast, IAE was unaffected by HCT, resulting in quantitative recovery for all levels evaluated. Precision and accuracy batches, as well as matrix effect evaluation, met acceptance criteria. CONCLUSION: The IAE procedure coupled with VAMS is immune to HCT biases affecting sampling volume and recovery.
Asunto(s)
Recolección de Muestras de Sangre/métodos , Adsorción , Cromatografía Líquida de Alta Presión , Pruebas con Sangre Seca , Hematócrito , Humanos , Naproxeno/sangre , Naproxeno/aislamiento & purificación , Ritonavir/sangre , Ritonavir/aislamiento & purificación , Sonicación , Espectrometría de Masas en TándemRESUMEN
Naproxen (NPX) is used in the treatment of rheumatoid arthritis (RA) for alleviation of pain and inflammation. In view of the extensive albumin binding of NPX, this study investigates whether chronic inflammation and sex influence the physiologic albumin concentrations, plasma protein binding, and pharmacokinetics (PK) of NPX. The PK of NPX was evaluated in a rat model of RA [collagen-induced arthritis (CIA) in Lewis rats] and in healthy controls. These PK studies included 1) NPX in female and male CIA rats that received 10, 25, or 50 mg/kg NPX i.p.; and 2) NPX in healthy female and male rats after i.p. dosing of NPX at 50 mg/kg. Plasma albumin concentrations were quantified by enzyme-linked immunosorbent assay, and protein binding was assessed using ultrafiltration. The NPX concentrations in plasma and filtrates were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma concentration-time data of NPX were first assessed by noncompartmental analysis (NCA). Nonlinear PK as indicated by dose-dependent NCA clearances and distribution volumes was observed. A two-compartment model with a first-order absorption process incorporating nonlinear protein binding in plasma and tissues jointly described the PK data of all groups. Saturable albumin binding accounts for the nonlinearity of NPX PK in all rats as well as part of the PK differences in arthritic rats. The CIA rats exhibited reduced albumin concentrations, reduced overall protein binding, and reduced clearances of unbound NPX, consistent with expectations during inflammation. The net effect of chronic inflammation was an elevation of the Cmax and area under the plasma concentration-time curve (AUC) of unbound drug.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacocinética , Artritis Experimental/sangre , Modelos Biológicos , Naproxeno/farmacocinética , Albúmina Sérica/metabolismo , Animales , Antiinflamatorios no Esteroideos/sangre , Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Experimental/inducido químicamente , Artritis Experimental/tratamiento farmacológico , Femenino , Masculino , Naproxeno/sangre , Naproxeno/uso terapéutico , Unión Proteica , Ratas Endogámicas Lew , Albúmina Sérica/análisis , Caracteres SexualesRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Andrographis paniculata Nees (Acanthacae) have broad range of pharmacological effects such as hepatoprotective, antifertility, antimalarial, antidiabetic, suppression of various cancer cells and anti-inflammatory properties and is widely used medicinal plant in the traditional Unani and Ayurvedic medicinal systems. Andrographolide (AN) is one of the active constituent of the A. paniculata Nees extract (APE). They have been found in many traditional herbal formulations in India and proven to be effective as anti-inflammatory drug. AIM OF THE STUDY: To evaluate the pharmacokinetic and pharmacodynamic (anti arthritic) herb-drug interactions of A. paniculata Nees extract (APE) and pure andrographolide (AN) with naproxen (NP) after oral co-administration in wistar rats. MATERIALS AND METHODS: After oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with NP (7.5mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of Cmax, tmax, t1/2, MRT, Vd, CL, and AUC were calculated by non-compartment model. Change in paw volume, mechanical nociceptive threshold, mechanical hyperalgesia, histopathology and hematological parameters were evaluated to study antiarthritic activity. RESULTS: Co-administration of NP with APE and pure AN decreased systemic exposure level of NP in vivo. The Cmax, tmax, AUC0-t of NP was decreased. In pharmacodynamic study, NP (10mg/kg) alone and NP+AN (10+60mg/kg) groups exhibited significant synergistic anti-arthritic activity as compared to groups NP+APE, APE and AN alone. CONCLUSION: The results obtained from this study suggested that NP, APE and pure AN existed pharmacokinetic herb-drug interactions in rat which is correlated with anti-arthritic study. The knowledge regarding possible herb-drug interaction of NP might be helpful for physicians as well as patients using AP. So further studies should be done to understand the effect of other herbal ingredients of APE on NP as well as to predict the herb-drug interaction in humans.
Asunto(s)
Andrographis/química , Antiinflamatorios no Esteroideos/farmacocinética , Artritis Experimental/tratamiento farmacológico , Diterpenos/administración & dosificación , Interacciones de Hierba-Droga , Naproxeno/farmacocinética , Extractos Vegetales/administración & dosificación , Administración Oral , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/sangre , Área Bajo la Curva , Artritis Experimental/sangre , Artritis Experimental/inducido químicamente , Artritis Experimental/fisiopatología , Cromatografía Líquida de Alta Presión , Diterpenos/aislamiento & purificación , Edema/inducido químicamente , Edema/prevención & control , Femenino , Adyuvante de Freund , Semivida , Hiperalgesia/inducido químicamente , Hiperalgesia/fisiopatología , Hiperalgesia/prevención & control , Tasa de Depuración Metabólica , Naproxeno/administración & dosificación , Naproxeno/sangre , Nocicepción/efectos de los fármacos , Dolor Nociceptivo/inducido químicamente , Dolor Nociceptivo/fisiopatología , Dolor Nociceptivo/prevención & control , Umbral del Dolor/efectos de los fármacos , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Ratas WistarRESUMEN
In this work, a novel microextraction technique using molecularly imprinted polymer-coated multi-walled carbon nanotubes (MIP-MWCNTs) in electromembrane extraction (EME) procedure is described. The method in combination with HPLC-UV was utilized to determine naproxen, as an acidic model drug, in urine, plasma and wastewater samples. For this purpose, MIP-MWCNTs were placed in the pores of polypropylene hollow fiber. The MIP-MWCNTs-EME method has the advantages of high selectivity and cleanup of MIP along with high enrichment ability of the EME in a single step extraction. Continuing with the research, optimization of the factors affecting the migration of naproxen from sample solutions to MIP-MWCNTs sites and then into the lumen of hollow fiber was explored. Under the optimized conditions, the limit of detection (LOD) of the developed method was calculated to be 0.3µgL-1. All relative standard deviations (RSDs) were lower than 3%. Linearity of the method was obtained within the range of 1-1000µgL-1 with the coefficient of determination (r2) being higher than 0.999. Under the optimized conditions, an extraction recovery of 66% was obtained, which corresponded to a preconcentration factor of 88. Finally, the developed method was satisfactorily used to determine naproxen in urine, plasma and wastewater samples.
Asunto(s)
Microextracción en Fase Líquida/métodos , Nanotubos de Carbono , Naproxeno/aislamiento & purificación , Polímeros , Electricidad , Límite de Detección , Impresión Molecular , Naproxeno/sangre , Naproxeno/orina , Polímeros/síntesis química , Polipropilenos , Aguas Residuales/química , Contaminantes Químicos del Agua/aislamiento & purificaciónRESUMEN
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used by the general population to alleviate inflammation and pain after oral surgeries. Piroxicam is among the most commonly used NSAIDs and excels in controlling pain, swelling, trismus and other common symptoms of inflammation. This study aimed to evaluate different concentrations of piroxicam and its major metabolite, 5'-hydroxypiroxicam, in human plasma samples over time using high performance liquid chromatography (HPLC) after liquid-liquid extraction. Briefly, 10 volunteers participated in this study after approval by the Ethics Committee of Bauru School of Dentistry, Universidade de São Paulo - USP, Brazil. Volunteers received a single dose oral of piroxicam (20 mg) and had blood collected at various times following an established protocol. The methodology of liquid-liquid extraction was effective for determining concentrations of piroxicam in plasma using HPLC in 10 out of 10 volunteers while 5'-hydroxypiroxicam was only detected in 2 out of 10 volunteers.
Asunto(s)
Antiinflamatorios no Esteroideos/sangre , Cromatografía Líquida de Alta Presión/métodos , Extracción Líquido-Líquido/métodos , Piroxicam/análogos & derivados , Piroxicam/sangre , Antiinflamatorios no Esteroideos/farmacocinética , Humanos , Naproxeno/sangre , Naproxeno/farmacocinética , Piroxicam/farmacocinética , Valores de Referencia , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
A sensitive and fast liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for the simultaneous quantification of naproxen and sumatriptan in human plasma. A simple liquid-liquid extraction procedure, with a mixture of ethyl acetate, methyl tert-butyl ether, and dichloromethane (4:3:3, v/v), was used for the cleanup of plasma. Naratriptan and aceclofenac were employed as internal standards. The analyses were carried out using an ACE C18 column (50 × 4.6 mm i.d.; particle size 5 µm) and a mobile phase consisting of 2 mM aqueous ammonium acetate with 0.025 % formic acid and methanol (38:62, v/v). A triple-quadrupole mass spectrometer equipped with an electrospray source in the positive mode was set up in the selective reaction monitoring mode to detect the ion transitions m/z 231.67 â m/z 185.07, m/z 296.70 â m/z 157.30, m/z 354.80 â m/z 215.00, and m/z 336.80 â m/z 97.94 for naproxen, sumatriptan, aceclofenac, and naratriptan, respectively. The method was validated and proved to be linear, accurate, precise, and selective over the ranges of 2.5-130 µg mL(-1) for naproxen and 1-50 ng mL(-1) for sumatriptan. The validated method was successfully applied to a pharmacokinetic study with simultaneous administration of naproxen sodium and sumatriptan succinate tablet formulations in healthy volunteers.
Asunto(s)
Cromatografía Liquida/métodos , Naproxeno/sangre , Sumatriptán/sangre , Espectrometría de Masas en Tándem/métodos , Humanos , Naproxeno/farmacocinética , Plasma/química , Sumatriptán/farmacocinéticaRESUMEN
Estimating the influence of interfering compounds present in the biological matrix on the determination of an analyte is one of the most important tasks during bioanalytical method development and validation. Interferences from endogenous components and, if necessary, from major metabolites as well as possible co-administered medications should be evaluated during a selectivity test. This paper describes a simple, rapid and cost-effective HPLC-UV method for the determination of naproxen in human plasma in the presence of two other analgesics, ibuprofen and paracetamol. Sample preparation is based on a simple liquid-liquid extraction procedure with a short, 5 s mixing time. Fenoprofen, which is characterized by a similar structure and properties to naproxen, was first used as the internal standard. The calibration curve is linear in the concentration range of 0.5-80.0 µg/mL, which is suitable for pharmacokinetic studies following a single 220 mg oral dose of naproxen sodium. The method was fully validated according to international guidelines and was successfully applied in a bioequivalence study in humans. Copyright © 2015 John Wiley & Sons, Ltd.
Asunto(s)
Acetaminofén/sangre , Antiinflamatorios no Esteroideos/sangre , Cromatografía Líquida de Alta Presión/métodos , Ibuprofeno/sangre , Naproxeno/sangre , Espectrofotometría Ultravioleta/métodos , HumanosRESUMEN
Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used by the general population to alleviate inflammation and pain after oral surgeries. Piroxicam is among the most commonly used NSAIDs and excels in controlling pain, swelling, trismus and other common symptoms of inflammation. This study aimed to evaluate different concentrations of piroxicam and its major metabolite, 5'-hydroxypiroxicam, in human plasma samples over time using high performance liquid chromatography (HPLC) after liquid-liquid extraction. Briefly, 10 volunteers participated in this study after approval by the Ethics Committee of Bauru School of Dentistry, Universidade de São Paulo - USP, Brazil. Volunteers received a single dose oral of piroxicam (20 mg) and had blood collected at various times following an established protocol. The methodology of liquid-liquid extraction was effective for determining concentrations of piroxicam in plasma using HPLC in 10 out of 10 volunteers while 5'-hydroxypiroxicam was only detected in 2 out of 10 volunteers.
Asunto(s)
Humanos , Piroxicam/análogos & derivados , Piroxicam/sangre , Antiinflamatorios no Esteroideos/sangre , Cromatografía Líquida de Alta Presión/métodos , Extracción Líquido-Líquido/métodos , Valores de Referencia , Factores de Tiempo , Piroxicam/farmacocinética , Antiinflamatorios no Esteroideos/farmacocinética , Naproxeno/sangre , Naproxeno/farmacocinética , Reproducibilidad de los ResultadosRESUMEN
Two simple, rapid and sensitive spectrophotometric methods have been developed for the determination of naproxen in pure, pharmaceutical preparation and human serum samples. These methods are based on the formation of yellow ion-pair complexes between naproxen and two sulfophthalein acid dyes, namely bromocresol green (BCG method) and bromothymol blue (BTB method). The resulting complexes were measured at 424 nm (BCG method) and at 422 nm (BTB method). The effects of variables such as reagent concentration and reaction time were investigated to optimize the procedure. Beer's law was obeyed in the concentration range of 10-105 µg/mL and 5-85 µg/mL and the detection limits were found to be 0.347 and 0.31 µg/mL for BCG and BTB methods, respectively. The developed methods have been successfully applied for the determination of naproxen in bulk drugs, pharmaceutical formulations and human serum samples with good accuracy and precision. The results are comparable to those of reference methods, and hence are recommended for quality control and routine analysis.
Asunto(s)
Naproxeno/análisis , Espectrofotometría/métodos , Verde de Bromocresol , Azul de Bromotimol , Humanos , Concentración de Iones de Hidrógeno , Naproxeno/sangre , Comprimidos/análisisRESUMEN
BACKGROUND: HCP1004 is a newly developed fixed-dose combination of naproxen (500 mg) and esomeprazole strontium (20 mg) that is used in the treatment of rheumatic diseases and can reduce the risk of nonsteroidal anti-inflammatory drug-associated ulcers. The aim of this study was to evaluate the pharmacokinetics (PK) and safety of HCP1004 compared to VIMOVO(®) (a marketed fixed-dose combination of naproxen and esomeprazole magnesium). SUBJECTS AND METHODS: An open-label, randomized, two-treatment, two-sequence crossover, single-dose clinical study was conducted in 70 healthy volunteers. In each period, a reference (VIMOVO(®)) or test (HCP1004) drug was administered orally, and serial blood samples for PK analysis were collected up to 72 hours after dosing. To evaluate the PK profiles, the maximum plasma concentration (Cmax) and the area under the concentration-time curve from 0 to the last measurable time (AUC0-t) were estimated using a noncompartmental method. Safety profiles were evaluated throughout the study. RESULTS: Sixty-six of the 70 subjects completed the study. The Cmax (mean ± standard deviation) and AUC0-t (mean ± standard deviation) for naproxen in HCP1004 were 61.67 ± 15.16 µg/mL and 1,206.52 ± 166.46 h · µg/mL, respectively; in VIMOVO(®); these values were 61.85 ± 14.54 µg/mL and 1,211.44 ± 170.01 h · µg/mL, respectively. The Cmax and AUC0-t for esomeprazole in HCP1004 were 658.21 ± 510.91 ng/mL and 1,109.11 ± 1,111.59 h · ng/mL, respectively; for VIMOVO(®), these values were 595.09 ± 364.23 ng/mL and 1,015.12 ± 952.98 h · ng/mL, respectively. The geometric mean ratios and 90% confidence intervals (CIs) (HCP1004 to VIMOVO(®)) of the Cmax and AUC0-t of naproxen were 0.99 (0.94-1.06) and 1.00 (0.98-1.01), respectively. For esomeprazole, the geometric mean ratios (90% CI) for the Cmax and AUC0-t were 0.99 (0.82-1.18) and 1.04 (0.91-1.18), respectively. The overall results of the safety assessment showed no clinically significant issues for either treatment. CONCLUSION: The PK of HCP1004 500/20 mg was comparable to that of VIMOVO(®) 500/20 mg for both naproxen and esomeprazole after a single oral dose. Both drugs were well-tolerated without any safety issues.