RESUMO
Green spectrophotometric and HPLC methods have been developed for the quantification of metoclopramide. In the spectrophotometric method, it was determined by direct absorbance measurement at 273 nm wavelength using ultrapure water as solvent. The Extend C18 column was used for the HPLC method. The mobile phase system consisted of a combination of ethanol and formic acid solution (pH 2.0; 30:70 v/v). Isocratic elution was applied and the flow rate was set at 1.0 mL min-1. Metoclopramide was detected at 273 nm. The methods performed were economical, rapid, environmentally friendly, and simple, providing metoclopramide analysis within 5 min. The methods have been successfully applied in pharmaceutical products without matrix interference. The results of the application of the developed methods to pharmaceutical products were statistically compared and no significant difference was observed between the methods. In addition, the greenness assessment of the developed methods was performed using AGREE software. Our developed methods, based on the use of solvents such as ethanol and water, are proposed as a more environmentally and analyst-friendly option for the quantification of metoclopramide in pharmaceutical products than other methods currently in use.
Assuntos
Etanol , Metoclopramida , Cromatografia Líquida de Alta Pressão/métodos , Metoclopramida/análise , Água , Preparações FarmacêuticasRESUMO
Chrozophora tinctoria (L.) A.Juss. is herbaceous, monecious annual plant used traditionally to cure gastrointestinal disorders. The present study was carried out to find the bioactive compounds by Gas Chromatography-Mass Spectrometry, the acetylcholinesterase inhibitory potential acute toxicity, and emetic activity present in the ethyl acetate fraction of Chrozophora tinctoria (EAFCT) and dichloromethane fraction of Chrozophora tinctoria (DCMFCT). The compounds detected in both fractions were mostly fatty acids, with about seven compounds in EAFCT and 10 in DCMFCT. These included pharmacologically active compounds such as imipramine, used to treat depression, or hexadecanoic acid methyl ester, an antioxidant, nematicide, pesticide, hypocholesterolemic, 9,12,15-Octadecatrienoic acid, ethyl ester, (Z,Z,Z)- is used as a cancer preventive, antiarthritic, antihistaminic, hepatoprotective, insectifuge, nematicide, Pentadecanoic acid, 14-methyl-, methyl ester have antifungal, antimicrobial and antioxidant activities, 10-Octadecanoic acid, methyl ester have the property to decrease blood cholesterol, Antioxidant and antimicrobial, 1-Eicosanol is used as an antibacterial, 1-Hexadecene has antibacterial, antioxidant, and antifungal activities. Both DCMFCT and EAFCT fractions inhibited acetylcholinesterase (AChE) activity with IC50 values of 10 µg and 130 µg, respectively. Both the fractions were found to be toxic in a dose-dependent manner, inducing emesis at 0.5g onward and lethargy and mortality from 3-5 g upwards. Both the fractions combined with distilled water showed highly emetic activity. The significant increase in the number of vomits was shown by EAFCT plus distilled water which are 7.50±1.29, 7.25±3.10, and 11.75±2.22 number of vomits at 1g, 2g, and 3g/kg concentration respectively, while DCMFCT plus distilled water showed 5.25±2.22, 7.50±2.52 and 10.25±2.22 number of vomits at 1g, 2, and 3g/kg correspondingly. The antiemetic standard drug metoclopramide has a higher impact against the emesis induced by both the fractions than dimenhydrinate. Metoclopramide decreases the number of vomits caused by EAFCT to 1.00±0.00, 2.00±0.00, 4.00±1.00 at 1g, 2, and 3g/kg sequentially, while dimenhydrinate decreases the number of vomits to 1.33±0.58, 2.33±1.15, 4.33±0.58 at 1g, 2, and 3g respectively. In the same way, Metochloprimide decreases the number of emesis caused by DcmCt from 5.25±2.22, 7.50±2.52, 10.25±2.22 to 1.33±0.58, 2.33±1.1, 4.33±0.58 at 1g, 2, and 3g/kg concentrations. The present study is the first documented report that scientifically validates the folkloric use of Chrozophora tinctoria as an emetic agent.
Assuntos
Dimenidrinato , Euphorbiaceae , Acetilcolinesterase , Animais , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Dimenidrinato/análise , Eméticos/análise , Ésteres/análise , Cromatografia Gasosa-Espectrometria de Massas , Metoclopramida/análise , Modelos Animais , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Vômito , ÁguaRESUMO
Elneopa NF No. 1 and No. 2 infusions are total parenteral nutrition solutions packaged in four-chambered infusion bags. They have been used as home parenteral nutrition, with various drugs injected into the infusion bags, for treating patient symptoms. In this study, we investigated the stability of six drugs, including famotidine, scopolamine butylbromide, furosemide, bromhexine hydrochloride, betamethasone sodium phosphate, and metoclopramide hydrochloride in the infusion bags under dark conditions at 4â for 7 days. Additionally, we developed a high-performance liquid chromatography method to determine drug concentrations in the infusions. The concentrations of injected famotidine, scopolamine butylbromide, and betamethasone sodium phosphate remained unchanged when the four chambers of Elneopa NF No. 1 and No. 2 were opened and the infusions were mixed. Their respective concentrations in the upper and lower chambers also remained unchanged. The concentration of furosemide in the upper chamber of the No. 1 infusion bag decreased after 5 days, although no change was observed in the other chambers and the mixed infusions with the four chambers opened. The concentration of bromhexine hydrochloride slightly decreased in the upper chambers (approximately 3%) after the co-infusion but decreased significantly in the other chambers and the mixed infusions with the four chambers opened. The concentration of metoclopramide hydrochloride significantly decreased in the upper chambers after the co-infusion; however, no change in concentration was observed in the other chambers and the mixed infusion with the four chambers opened. The results of this study provide useful information on home-based parenteral nutrition.
Assuntos
Betametasona/análogos & derivados , Bromoexina , Brometo de Butilescopolamônio , Embalagem de Medicamentos , Famotidina , Furosemida , Metoclopramida , Soluções de Nutrição Parenteral/análise , Nutrição Parenteral Total no Domicílio , Betametasona/análise , Bromoexina/análise , Brometo de Butilescopolamônio/análise , Estabilidade de Medicamentos , Famotidina/análise , Furosemida/análise , Metoclopramida/análiseRESUMO
In the recent drug analysis arena, optimizing a green, eco-friendly, and cost-effective technique is the main target. In order to cope with green analytical chemistry principles and the trending development of miniaturized portable and handheld devices, an innovative microfabricated ion-selective electrode for the analysis of metoclopramide (MTP) was developed. The fabricated electrode adopted a two-step optimization process. The first step of optimization depended on screening different ionophores in order to enhance the sensor selectivity. Calix-4-arene showed the maximal selectivity towards MTP. The second step was utilizing a graphene nanocomposite as an ion-to-electron transducer layer between the calix-4-arene polymeric membrane and the microfabricated copper solid-contact ion-selective electrode. The graphene nanocomposite layer added more stability to electrode potential drift and short response times (10 s), probably due to the hydrophobic behavior of the graphene nanocomposite, which precludes the formation of a water layer at the Cu electrode/polymeric membrane interface. The proposed MTP sensor has been characterized according to IUPAC recommendations and the linear dynamic range estimated to be 1 × 10-6 to 1 × 10-2 M with LOD of 3 × 10-7 M. The proposed sensor has been successfully employed in the selective determination of MTP in bulk powder, pharmaceutical formulation, and biological fluid. No statistical significant difference was observed upon comparing the results with those of the official method. The Eco-score of the method was assessed using the Eco-Scale tool and was compared with that of the official method. Graphical abstract.
Assuntos
Antagonistas dos Receptores de Dopamina D2/análise , Grafite/química , Metoclopramida/análise , Transdutores , Antagonistas dos Receptores de Dopamina D2/sangue , Desenho de Equipamento , Humanos , Limite de Detecção , Metoclopramida/sangue , Microtecnologia , Nanocompostos/química , Potenciometria/instrumentaçãoRESUMO
A novel ecofriendly, cost and time saving high-performance thin-layer chromatographic method was developed and validated for simultaneous determination of metoclopramide, ergotamine, caffeine, and paracetamol in bulk and pharmaceutical formulation. The separation was carried out on silica gel plates, using ethyl acetate:ethanol:ammonia (9:1:0.1, v/v/v) as a developing system. Ultraviolet detection was carried out at 272 nm. The resulting retention times were 0.15, 0.36, 0.49, and 0.74 min for metoclopramide, ergotamine, caffeine, and paracetamol, respectively. The greenness profile assessment was achieved to the proposed method to evaluate its greenness characters to the environment with acceptable results. Validation parameters were checked according to International Conference of Harmonization guidelines to achieve the international requirements for quality control analysis of the proposed drugs.
Assuntos
Acetaminofen/análise , Cafeína/análise , Ergotamina/análise , Metoclopramida/análise , Cromatografia em Camada Fina , Composição de Medicamentos , Estrutura MolecularRESUMO
An analytical investigation was carried out to study the treatment and amplification of the spectral signals produced by critical concentrations with high accuracy and precision using two advanced approaches. The factorized-spectrum approach was applied through two novel methods which were: absorptivity centering technique via both: factorized zero order absorption spectrum (ACT-FSD0ΔA) and factorized ratio spectrum (ACT-FSRΔP). The proposed methods were found to be linear in the ranges of (15-100⯵g/mL) and (3-40⯵g/mL) for ASP and MTO, respectively. Those methods were compared to the methods following the geometrical standard addition approach: ratio H-point standard addition method (RHPSAM) and geometrical induced amplitude modulation (GIAM). The approaches were applied for the determination of the minor component metoclopramide in its mixture with the major component aspirin in the challengeable ratio of (1,90) respectively in a white multicomponent system. The results obtained from the proposed approaches were statistically compared with each other. The methods were validated according to ICH guidelines where the results were found to be within the acceptable limits. The methods were found to be accurate and reliable for the determination of metoclopramide critical concentration besides aspirin concentration. The results of single factor ANOVA analysis indicated that there is no significant difference among the developed methods. These methods provided simple resolution of this binary combination from synthetic mixtures and pharmaceutical preparation and can be conveniently adopted for routine quality control analysis.
Assuntos
Preparações Farmacêuticas/análise , Processamento de Sinais Assistido por Computador , Espectrofotometria/métodos , Aspirina/análise , Aspirina/química , Modelos Lineares , Metoclopramida/análise , Metoclopramida/química , Modelos Químicos , Modelos Estatísticos , Preparações Farmacêuticas/química , Reprodutibilidade dos TestesRESUMO
The present study involved segmental testing of hair in two clinical cases with known dosage histories. Hair analysis confirmed the first patient's exposure to the prescribed sertraline and citalopram for several months. Citalopram was generally distributed along the hair shaft in accordance with the drug ingestion period. By contrast, "false" positive results were observed for sertraline in distal hair segments, corresponding to a period of no sertraline exposure, which may indicate incorporation from sweat or sebum, which transport the drugs along the hair surface. The second patient received various drugs during her treatment for brain cancer. Metoclopramide, morphine, oxazepam, paracetamol, sumatriptan, tramadol, and zopiclone, which had been part of the therapy, were all detected in the proximal hair segment. The results of these two cases indicated that results-especially concerning the time of drug intake-must be interpreted with caution and allow for the possibility of incorporation from sweat or sebum.
Assuntos
Analgésicos/análise , Cabelo/química , Hipnóticos e Sedativos/análise , Inibidores Seletivos de Recaptação de Serotonina/análise , Vasoconstritores/análise , Acetaminofen/análise , Adulto , Antieméticos/análise , Compostos Azabicíclicos/análise , Citalopram/análise , Feminino , Toxicologia Forense , Cabelo/crescimento & desenvolvimento , Humanos , Metoclopramida/análise , Morfina/análise , Oxazepam/análise , Piperazinas/análise , Sertralina/análise , Sumatriptana/análise , Tramadol/análiseRESUMO
A flow injection spectrophotometric procedure employing merging zones is proposed for direct bromopride determination in pharmaceutical formulations and biological fluids. The proposed method is based on the reaction between bromopride and p-dimethylaminocinnamaldehyde (p-DAC) in acid medium, in the presence of sodium dodecyl sulfate (SDS), resulting in formation of a violet product (λmax=565nm). Experimental design methodologies were used to optimize the experimental conditions. The Beer-Lambert law was obeyed in a bromopride concentration range of 3.63×10(-7) to 2.90×10(-5)molL(-1), with a correlation coefficient (r) of 0.9999. The limits of detection and quantification were 1.07×10(-7) and 3.57×10(-7)molL(-1), respectively. The proposed method was successfully applied to the determination of bromopride in pharmaceuticals and human urine, and recoveries of the drug from these media were in the ranges 99.6-101.2% and 98.6-102.1%, respectively. This new flow injection procedure does not require any sample pretreatment steps.
Assuntos
Antagonistas de Dopamina/urina , Análise de Injeção de Fluxo/instrumentação , Metoclopramida/análogos & derivados , Espectrofotometria/instrumentação , Cinamatos/química , Antagonistas de Dopamina/análise , Monitoramento de Medicamentos/instrumentação , Desenho de Equipamento , Humanos , Limite de Detecção , Metoclopramida/análise , Metoclopramida/urina , Preparações Farmacêuticas/químicaRESUMO
Two simple analytical methods were developed and validated for the analysis of a binary mixture of metoclopramide (MET) and aspirin (ASP). The first method depends on measuring the first derivative amplitudes at 257 nm for MET and at 310 nm for ASP, respectively. The calibration graphs were linear in the range of 0.25-20.0 µg/mL for MET and 10.0-200.0 µg/mL for ASP. For the second method, good chromatographic separation was achieved using Promosil C18 column (250 × 4.6 mm i.d., 5 µm particle size). Mobile phase consisting of methanol and 0.02 M phosphate buffer in the ratio of 60:40 (v/v) at pH 4.0 was pumped at a flow rate of 1 mL/min with UV detection at 260 nm. Indapamide was used as an internal standard. The method showed good linearity over the concentration ranges of 0.20-10.0 and 10.0-200.0 µg/mL with limits of detection of 0.06, 1.81 µg/mL and limits of quantification of 0.17, 5.46 µg/mL for MET and ASP, respectively. The results of the proposed methods were statistically compared with those obtained by the official United States Pharmacopeia method revealing non-significant differences in the performance of the methods regarding accuracy and precision. The suggested methods were successfully applied for the simultaneous analysis of the studied drugs in their co-formulated tablets as well as in their single dosage forms.
Assuntos
Aspirina/análise , Cromatografia Líquida de Alta Pressão/métodos , Metoclopramida/análise , Análise Espectral/métodos , Aspirina/química , Concentração de Íons de Hidrogênio , Limite de Detecção , Modelos Lineares , Metoclopramida/química , Reprodutibilidade dos Testes , Comprimidos/químicaRESUMO
A novel, fast, sensitive and specific technique using capillary electrophoresis coupled to a diode array detector has been developed for the separation and simultaneous determination of two antimigraine mixtures in tablet formulation. The two combinations are ergotamine tartrate (ERG), caffeine (CAF) and paracetamol (PAR) with either domperidone (DOM), combination (I) or metoclopramide (MET), combination (II). The proposed method utilized a fused silica capillary (55 cm × 75 µm i.d.) and background electrolyte composed of phosphate buffer (25 mM, pH 9.8). The separation was achieved at 20 KV applied voltage and at 25°C. The described method was linear over the range of 1-80 and 2-100 µg/mL for CAF and MET, respectively, and 1-80 µg/mL for DOM, ERG and PAR. Intra-day and inter-day relative standard deviation (n = 5) was ≤1.10%. The limits of detection of CAF and PAR were 0.20 and 0.10 µg/mL, respectively, and 0.50 µg/mL for MET, DOM and ERG. Other aspects of analytical validation were also evaluated. The proposed method was successfully applied to the analysis of the two combinations in their tablets. Therefore, the proposed method is suitable for the routine control of these ingredients in multicomponent dosage forms.
Assuntos
Acetaminofen/análise , Cafeína/análise , Domperidona/análise , Ergotamina/análise , Metoclopramida/análise , Acetaminofen/química , Cafeína/química , Domperidona/química , Combinação de Medicamentos , Estabilidade de Medicamentos , Eletroforese Capilar/métodos , Ergotamina/química , Concentração de Íons de Hidrogênio , Limite de Detecção , Modelos Lineares , Metoclopramida/química , Transtornos de Enxaqueca , Concentração Osmolar , Reprodutibilidade dos Testes , Comprimidos/química , Tartaratos/química , TemperaturaRESUMO
É relatado o caso de um paciente do sexo masculino, de 1 ano e 2 meses, apresentando quadro de fasceíte necrotizante comprometendo região inguinal e coxas após injeção intramuscular de metoclopramida. Neste artigo, são discutidos e apontados os aspectos fundamentais do diagnóstico e tratamento da doença, ressaltando a importância da identificação precoce dos fatores que possam contribuir significativamente para melhora da sobrevida.
We report the case of a 1-year-old boy who developed necrotizing fasciitis of the groin and thighs after intramuscular injection of metoclopramide. We discuss and highlight the key aspects of diagnosis and treatment of this disease, with an emphasis on the importance of early identification of factors that can contribute significantly to improved survival.
Assuntos
Humanos , Masculino , Criança , Infecções Bacterianas , Desbridamento , Técnicas e Procedimentos Diagnósticos , Fasciite Necrosante/cirurgia , Complicações Intraoperatórias , Infecções Estafilocócicas/cirurgia , Metoclopramida/análise , Diagnóstico , Injeções Intramusculares , Métodos , PacientesRESUMO
A simple, sensitive and inexpensive electrochemical method was developed for the determination of metoclopramide (MCP) with a multi-wall carbon nanotube (MWNT) modified glassy carbon electrode (GCE). MWNT was dispersed into polyacrylic acid (PAA); the aqueous suspension was then cast on GCE electrodes, forming MWNT-PAA films after evaporation of the solvent. The electrochemical behavior of MCP at the MWNT-modified electrode was investigated in detail. Compared with the bare GCE, the MWNT-modified electrode exhibits electrocatalytic activity to the oxidation of MCP because of the significant oxidation peak-current enhancement. Furthermore, various experimental parameters, such as the solution pH value, the amount of MWNT-PAA suspension and accumulation conditions were optimized for the determination of MCP. Based on the electrocatalytic effect of the MWNT-modified electrode, linear sweep voltammetry (LSV) was developed for the determination of MCP with the linear response in the range from 1.0 × 10(-7) to 1.0 × 10(-5) mol L(-1) and a detection limit of 5.0 × 10(-8) mol L(-1). The method has been successfully applied to the determination of MCP in commercial MCP tablets.
Assuntos
Eletroquímica/métodos , Metoclopramida/análise , Metoclopramida/química , Nanotubos de Carbono/química , Resinas Acrílicas/química , Calibragem , Eletroquímica/instrumentação , Eletrodos , Vidro/química , Concentração de Íons de Hidrogênio , ComprimidosRESUMO
The objective of this study is to develop sensitive and cost effective reverse phase high performance liquid chromatographic method for the estimation of Metoclopramide Hydrochloride in oral solid dosage formulations. A reverse chromatographic method was used with the mobile phase of Acetonitrile, 20m M Potassium dihydrogen phosphate buffer solution (pH 3 adjusted with orthophosphoric acid) in the ratio of 40:60. The column used was Waters C18 3.9×300mm µBondapak (RP). The flow rate of the mobile phase was 2ml/minute. The detector was set at the wavelength of 275nm.This method showed good sensitivity. The linearity was also found to be excellent (γ(2)=0.997) in the range of 5-75 µg/ml. No interfering peaks were observed at the retention time of Metoclopramide Hydrochloride when both placebo and blank samples were injected (Retention time =1.93min). The parameters such as specificity, linearity, range, accuracy, precision, system suitability, solution stability, detection and quantification limits were evaluated to validate this method. This method can effectively be used for quantitative analysis of Metoclopramide hydrochloride tablet formulations because of its specificity, accuracy and convenience of use.
Assuntos
Química Farmacêutica/métodos , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Metoclopramida/análise , Comprimidos/química , Química Farmacêutica/estatística & dados numéricos , Estabilidade de Medicamentos , Limite de DetecçãoRESUMO
A new, simple and accurate spectrofluorimetric method for the determination of metoclopramide hydrochloride was developed. The metoclopramide hydrochloride can remarkably enhance the luminescence intensity of the Tb(3+) ion doped in PMMA matrix at λ(ex)=360 nm in methanol at pH 6.9. The intensity of the emission band at 545 nm of Tb(3+) ion doped in PMMA matrix is increased due to the energy transfer from metoclopramide hydrochloride to Tb(3+) in the excited stated. The effect of different parameters, e.g., pH, temperature, Tb(3+) concentration, foreign ions that control the fluorescence intensity of the produced ion associate was critically investigated. The calibration curve of the emission intensity at 545 nm shows linear response of metoclopramide over a concentration range of 5 × 10(-5)-5.0 × 10(-8) M with detection limit of 8.7 × 10(-10) M. The method was used successfully for the determination of metoclopramide in pharmaceutical preparations and human serum. The average recovery of 99.48% with standard deviation of 0.32% and 96.98% with standard deviation of 0.4%, of pharmaceutical preparations and human serum respectively, were obtained which compared will with the results obtained from standard LC method of average recovery 99.04% and standard deviation of 0.6% and average recovery of 98.19% with standard deviation of 0.6% of pharmaceutical preparations and human serum, respectively.
Assuntos
Metoclopramida/análise , Fenômenos Ópticos , Polimetil Metacrilato/química , Espectrometria de Fluorescência/métodos , Térbio/química , Absorção , Humanos , Limite de Detecção , Modelos Lineares , Preparações Farmacêuticas/químicaRESUMO
The combination of Fourier transform infrared (FT-IR) microspectroscopy with a thermal analyzer was applied to quickly investigate the solid-state ion-exchange reaction of metoclopramide HCl monohydrate (MCP H(2)O) by clipping MCP H(2)O powder between two KBr or KCl pellets. The physical and ground mixtures of MCP H(2)O or 150 °C-preheated MCP powder and KBr or KCl powders with a weight ratio of 1 : 100 were also prepared and determined by FT-IR microspectroscopy. The samples of MCP H(2)O or 150 °C-preheated MCP were identified by using differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis. The results of present study indicate that the ion-exchange reaction was easily induced between MCP H(2)O and KBr by grinding and heating processes. The possible mechanism of ion-exchange reaction may take place between the HCl salt of MCP H(2)O and a KBr matrix by grinding or heating to yield a mixture of HCl and HBr salts of the MCP sample in the presence of hydrated water. The crystal hydrate played an important role to improve this ion-exchange reaction between MCP H(2)O and KBr. However, no ion-exchange reaction occurred between MCP H(2)O and KCl or between 150 °C-preheated MCP and KBr. The solid-state ion-exchange reaction was more easily determined by this novel thermal FT-IR microspectroscopy than other conventional methods.
Assuntos
Brometos/análise , Troca Iônica , Metoclopramida/análise , Compostos de Potássio/análise , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Varredura Diferencial de Calorimetria/métodos , Temperatura AltaRESUMO
A simple, sensitive and selective spectrofluorimetric method for the determination of Metoclopramide hydrochloride (MCP) is developed. The MCP can remarkably enhances the luminescence intensity of the Eu(3+) ion doped in sol-gel matrix at lambda(ex)=380 nm in DMSO at pH 8.7. The intensity of the emission band of Eu(3+) ion doped in sol-gel matrix increases due to energy transfer from MCP to Eu(3+) in the excited state. The enhancement of the emission band of Eu(3+) ion doped in sol-gel matrix at 617 nm was found to be directly proportional to the concentration of MCP with a dynamic range of 5 x 10(-9) - 1.0 x 10(-6) mol L(-1) and detection limit of 2.2 x10(-11) mol L(-1).
Assuntos
Antagonistas de Dopamina/análise , Európio/química , Metoclopramida/análise , Preparações Farmacêuticas/química , Espectrometria de Fluorescência/métodos , Absorção , Antagonistas de Dopamina/sangue , Transferência de Energia , Humanos , Concentração de Íons de Hidrogênio , Ligantes , Metoclopramida/sangue , Solventes/química , ComprimidosRESUMO
Metoclopramide (MCP) is frequently used to treat gastroparesis. Previous studies have documented MCP metabolism, but systematic structural identification of metabolites has not been performed. The aim of this study was to better understand MCP metabolism in humans. For examination of in vivo metabolism, a single oral 20-mg MCP dose was administered to eight healthy male volunteers, followed by complete urine collection over 24 h. In vitro incubations were performed in human liver microsomes (HLM) to characterize metabolism via cytochromes P450 and UDP-glucuronosyltransferases and in human liver cytosol for metabolism via sulfotransferases. Urine and subcellular incubations were analyzed for MCP metabolites on a mass spectrometer with accurate mass measurement capability. Five MCP metabolites were detected in vivo, and five additional metabolites were detected in vitro. The five metabolites of MCP identified both in vitro and in vivo were an N-O-glucuronide (M1), an N-sulfate (M2), a des-ethyl metabolite (M3), a hydroxylated metabolite (M4), and an oxidative deaminated metabolite (M5). To our knowledge, metabolites M1 and M4 have not been reported previously. M2 urinary levels varied 22-fold and M3 levels varied 16-fold among eight subjects. In vitro studies in HLM revealed the following additional metabolites: two ether glucuronides (M6 and M8), possibly on the phenyl ring after oxidation, an N-glucuronide (M7), a carbamic acid (M9), and a nitro metabolite (M10). Metabolites M6 to M10 have not been reported previously. In conclusion, this study describes the identification of MCP metabolites in vivo and in vitro in humans.
Assuntos
Metoclopramida/metabolismo , Antieméticos/análise , Antieméticos/química , Antieméticos/metabolismo , Antieméticos/urina , Citosol/metabolismo , Humanos , Masculino , Metoclopramida/análise , Metoclopramida/química , Metoclopramida/urina , Microssomos Hepáticos/metabolismo , NADP/metabolismoRESUMO
A rapid, simple, and highly sensitive second derivative synchronous fluorometric method has been developed for the simultaneous determination of metoclopramide (MT) and pyridoxine (PY) in a binary mixture. The method is based on measurement of the native fluorescence of these drugs at delta lambda = 80 nm in methanol. The different experimental parameters affecting the native fluorescence of the drugs were carefully studied and optimized. The fluorescence-concentration plots were rectilinear over the ranges of 0.02-0.4 and 0.1-2 microg/mL for MT and PY, respectively. The limits of detection were 0.003 and 0.007 microg/mL and the limits of quantification were 0.008 and 0.02 microg/mL for MT and PY, respectively. The proposed method was successfully applied to the determination of MT and PY in synthetic mixtures and in commercial syrup. The results were in good agreement with those obtained with a reported method. The high sensitivity attained by the proposed method allowed the determination of MT in spiked and real human plasma samples. The mean percent recoveries of MT from spiked and real human plasma (n = 3) were 93.72 +/- 3.15 and 89.72 +/- 2.19 respectively.
Assuntos
Metoclopramida/análise , Metoclopramida/sangue , Piridoxina/análise , Piridoxina/sangue , Espectrometria de Fluorescência/métodos , Antieméticos/análise , Antieméticos/sangue , Análise Química do Sangue/métodos , Análise Química do Sangue/estatística & dados numéricos , Química Farmacêutica , Combinação de Medicamentos , Humanos , Sensibilidade e Especificidade , Espectrometria de Fluorescência/estatística & dados numéricos , SuspensõesRESUMO
A novel method for the determination of metoclopramide (MCP) using electrogenerated chemiluminescence (ECL) is presented. A tris(2,2'-bipyridyl)dichlororuthenium(II) (Ru(bpy)3(2+))-doped silica (RuDS) nanoparticle/perfluoinated ion-exchange resin (Nafion) with nanocomposite membrane modified glassy carbon electrode (GCE) is used. The Ru(bpy)3(2+) encapsulation interior of the silica nanoparticle maintains its electrochemical activities and also reduces Ru(bpy)3(2+) leaching from the silica matrix when immersed in water due to the electrostatic interaction. The analytical performance of this ECL sensor for MCP is shown in detail. Under optimal experimental conditions, it has good linearity in the concentration range from 2 x 10(-8)mol/L to 1 x 10(-5)mol/L (R=0.9989) with a detection limit of 7 x 10(-9)mol/L. The relative standard deviation (n=11) is 3.2% for detecting 1.2 x 10(-6)mol/L MCP. The recoveries are in the range of 97.0-104.4% for sample measurements by standard-addition method. This method has been applied successfully to determine MCP in pharmaceutical preparations and in human urine. Statistical analysis (Student's t-test and variance ratio F-test) of the obtained results show no significant difference between this proposed method and the reference method.
Assuntos
Carbono , Antagonistas de Dopamina/análise , Polímeros de Fluorcarboneto/química , Metoclopramida/análise , Nanopartículas/química , Antagonistas de Dopamina/urina , Eletroquímica/instrumentação , Eletroquímica/métodos , Eletrodos , Vidro/química , Humanos , Medições Luminescentes , Metoclopramida/urina , Nanopartículas/ultraestrutura , Tamanho da Partícula , Padrões de Referência , Compostos de Rutênio/química , Sensibilidade e Especificidade , Dióxido de Silício/químicaRESUMO
A reversed-phase ion-pair HPLC method with ultraviolet detection has been developed for determination of metoclopramide (MCP) in bovine and swine muscle, liver, kidney, fat and intestine. MCP was extracted from samples with acetonitrile, and the extracts were cleaned up on an Oasis HLB cartridge (60 mg) after liquid-liquid extraction. The limit of detection of MCP was 0.002 microg/g and the limit of quantitation was 0.007 microg/g. Recoveries of MCP spiked at 0.03 ppm ranged from 74.1 to 93.3% for bovine tissues and from 86.1 to 92.7% for swine tissues. The present method was used for the analysis of bovine and swine tissues 1 day after withdrawal following drug administration. The MCP concentrations in all tissues were lower than the Japanese provisional MRLs.