RESUMEN
Additive manufacturing is a technique that allows the construction of prototypes and has evolved a lot in the last 20 years, innovating industrial fabrication processes in several areas. In chemistry, additive manufacturing has been used in several functionalities, such as microfluidic analytical devices, energy storage devices, and electrochemical sensors. Theophylline and paracetamol are important pharmaceutical drugs where overdosing can cause adverse effects, such as tachycardia, seizures, and even renal failure. Therefore, this paper aims at the development of miniaturized electrochemical sensors using 3D printing and polylactic acid-based conductive carbon black commercial filament for theophylline and paracetamol detection. Electrochemical characterizations of the proposed sensor were performed to prove the functionality of the device. Morphological characterizations were carried out, in which chemical treatment could change the surface structure, causing the improvement of the analytical signal. Thus, the detection of theophylline at a linear range of 5.00-150 µmol L-1 with a limit of detection of 1.2 µmol L-1 was attained, and the detection of paracetamol at a linear range of 1.00-200 µmol L-1 with a limit of detection of 0.370 µmol L-1 was obtained, demonstrating the proposed sensor effectively detected pharmaceutical drugs.
Asunto(s)
Acetaminofén , Técnicas Electroquímicas , Poliésteres , Hollín , Teofilina , Acetaminofén/análisis , Hollín/química , Técnicas Electroquímicas/métodos , Teofilina/análisis , Poliésteres/química , Límite de Detección , Impresión Tridimensional , MiniaturizaciónRESUMEN
Cacao seeds, Theobroma cacao, provide the basis for a ceremonially important Mesoamerican food. Past efforts to identify cacao in ceramics focused on highly decorative vessel forms associated with elite ceremonial contexts, creating assumptions as to how cacao was distributed and who could access it. This study examines 54 archaeological ceramic sherds from El Pilar (Belize/Guatemala) of Late Classic (600 to 900 CE) residential and civic contexts representing a cross-section of ancient Maya inhabitants. Identification of cacao in ancient sherds has depended on the general presence of theobromine; we used the discrete presence of theophylline, a unique key biomarker for cacao in the region. Analysis was done by grinding off all outside surfaces to reduce contamination, pulverizing the inner clay matrix, extracting absorbed molecules, and concentrating the extractions. In order to obtain especially high selectivity and low limits of detection, our study utilized the technique of resonance-enhanced multiphoton ionization coupled with laser-desorption jet-cooling mass spectrometry. This technique isolates molecules in the cold gas phase where they can be selectively ionized through a resonant two-photon process. Of the sherds analyzed, 30 samples (56%) were found to contain significant amounts of theophylline and thus test positive for cacao. Importantly, cacao is present in all contexts, common to all Maya residents near and far from centers.
Asunto(s)
Cacao , Belice , Cacao/anatomía & histología , Cacao/historia , Arcilla , Guatemala , Historia Antigua , Semillas/química , Teobromina/análisis , Teobromina/historia , Teofilina/análisis , Teofilina/historiaRESUMEN
In this work, the possibility of simultaneous determination of three compounds with a single-injection step using batch injection analysis with multiple pulse amperometric detection (BIA-MPA) is demonstrated for the first time. A sequence of three potential pulses (+1.25 V, +1.60 V, and +1.80 V) was applied with the acquisition of three separate amperograms. 8-Chlorotheophylline was detected selectively at +1.25 V, both 8-chlorotheophylline and pyridoxine at +1.60V and 8-chlorotheophylline, pyridoxine, and diphenhydramine at +1.80 V. Subtraction between the currents detected at the three amperograms (with the help of correction factors) was used for the selective determination of pyridoxine and diphenhydramine. The proposed method is simple, inexpensive, fast (60 injections h(-1)), and present selectivity for the determination of the three compounds in pharmaceutical samples, with results similar to those obtained by HPLC (95% confidence level).
Asunto(s)
Electroquímica/métodos , Inyecciones/métodos , Difenhidramina/análisis , Electroquímica/economía , Concentración de Iones de Hidrógeno , Teofilina/análogos & derivados , Teofilina/análisis , Factores de TiempoRESUMEN
Guarana seeds have the highest caffeine concentration among plants accumulating purine alkaloids, but in contrast with coffee and tea, practically nothing is known about caffeine metabolism in this Amazonian plant. In this study, the levels of purine alkaloids in tissues of five guarana cultivars were determined. Theobromine was the main alkaloid that accumulated in leaves, stems, inflorescences and pericarps of fruit, while caffeine accumulated in the seeds and reached levels from 3.3% to 5.8%. In all tissues analysed, the alkaloid concentration, whether theobromine or caffeine, was higher in young/immature tissues, then decreasing with plant development/maturation. Caffeine synthase activity was highest in seeds of immature fruit. A nucleotide sequence (PcCS) was assembled with sequences retrieved from the EST database REALGENE using sequences of caffeine synthase from coffee and tea, whose expression was also highest in seeds from immature fruit. The PcCS has 1083bp and the protein sequence has greater similarity and identity with the caffeine synthase from cocoa (BTS1) and tea (TCS1). A recombinant PcCS allowed functional characterization of the enzyme as a bifunctional CS, able to catalyse the methylation of 7-methylxanthine to theobromine (3,7-dimethylxanthine), and theobromine to caffeine (1,3,7-trimethylxanthine), respectively. Among several substrates tested, PcCS showed higher affinity for theobromine, differing from all other caffeine synthases described so far, which have higher affinity for paraxanthine. When compared to previous knowledge on the protein structure of coffee caffeine synthase, the unique substrate affinity of PcCS is probably explained by the amino acid residues found in the active site of the predicted protein.
Asunto(s)
Alcaloides/análisis , Cafeína/análisis , Metiltransferasas/metabolismo , Paullinia/química , Alcaloides/química , Alcaloides/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Cafeína/química , Cafeína/metabolismo , Frutas/química , Metilación , Metiltransferasas/genética , Estructura Molecular , Paullinia/genética , Hojas de la Planta/química , Purinas/análisis , Purinas/química , Semillas/química , Semillas/enzimología , Teobromina/análisis , Teobromina/química , Teobromina/aislamiento & purificación , Teofilina/análisis , Teofilina/química , Xantinas/análisis , Xantinas/químicaRESUMEN
A novel, simple, accurate and precise RP-HPLC method for simultaneous determination of levosalbutamol sulfate and theophylline has been developed and validated. Separation was achieved on a Phenomenex; C18 column (250 mm × 4.6 mm i.d., 5 µm) using methanol: 10 mM TBAHS(tetrabutyl ammonium hydrogen sulfate) (50:50, v/v) as mobile phase at flow rate of 1.0 mL.min-1. The UV detection wavelength was 274 nm. The linearity is obeyed over a concentration range of 0.5-150 µg.mL-1 with correlation coefficient of 0.999 for both the drugs. The proposed method was validated by determining accuracy, precision, stability and system suitability parameters. The method was found to be robust. Specificity of the method was determined by subjecting the drugs to various stress conditions like acid, alkali, oxidation, thermal and photolytic degradation. The method was used successfully for the simultaneous determination of levosalbutamol sulfate and theophylline in syrup dosage form.
Desenvolveu-se e validou-se método de RP-HPLC novo, simples, exato e preciso de determinação simultânea do sulfato de levossalbutamol e teofilina.. A separação foi efetuada em uma coluna Phenomenex; C18 (250 mm x 4,6 mm d.i., 5 µm) utilizando metanol: TBAHS (hidrogenossulfato de tetrabutilamônio) 10 mM (50:50, v/v) como fase móvel, com fluxo de 1,0 mL.min-1. O comprimento de onda de detecção no UV foi 274 nm. Observou-se linearidade na faixa de concentração de 0,5-150 µg mL-1, com coeficiente de correlação de 0,999 para ambos os fármacos. O método proposto foi validado determinando-se exatidão, precisão, estabilidade e parâmetros de adequação do sistema. O método mostrou-se robusto. A especificidade do método foi determinada submetendo os fármacos a várias condições de estresse, como ácido, álcali, oxidação, degradação térmica e fotolítica. O método foi usado com sucesso para a determinação simultânea do sulfato de levossalbutamol e teofilina na forma de xarope.
Asunto(s)
Teofilina/análisis , Cromatografía Líquida de Alta Presión/métodos , Levalbuterol/análisis , Formas de DosificaciónRESUMEN
The purpose of the present study was to investigate the interaction between ketotifen fumarate and anhydrous theophylline in aqueous media of various pH (1.2 and 6.8). Using Job's continuous-variation analysis and Ardon's spectrophotomeric measurement methods, the values of the stability constants of theophylline with ketotifen were determined at a fixed temperature (37 ºC) at various pH. The stability constants, ranging between 5.66 and 9.92, were derived from Ardon's plot, indicating that comparatively stable complexes had formed as a result of an interaction between the drugs. However, following the interaction of theophylline with ketotifen, stability constants were <1 at gastric pH (1.2) and intestinal pH (6.8). Concurrent administration of ketotifen and theophylline could result in the formation of a stable complex and this is likely to reduce the therapeutic activities of both drugs.
O objetivo do presente estudo foi investigar a interação entre o fumarato de cetotifeno e a teofilina anidra em meios aquosos com vários pH (1,2 e 6,8). Utilizando a análise da variação contínua de Job e os métodos de medida espectrofotométrica de Ardon, os valores das constantes de estabilidade da teofilina com o cetotifeno foram determinados em temperatura fixa (37 oC) em vários pH. As constantes de estabilidade, variando entre 5,66 e 9,92 derivaram-se a partir do delineamento de Ardon, indicando, comparativamente, que complexos estáveis se formaram como resultado da interação entre os fármacos. Entretanto, seguindo a interação da teofilina com o cetotifeno, as constantes de estabilidade foram <1, em pH gástrico (1,2) e intestinal (8,8). A administração concomitante de cetotifeno e teofilina poderia resultar na formação de complexo estável, o que reduz a atividade terapêutica de ambos os fármacos.
Asunto(s)
Técnicas In Vitro/métodos , Cetotifen/análisis , Teofilina/análisis , Reactividad-EstabilidadRESUMEN
Two spectrophotometric methods, assisted by chemometric tools, were developed for the determination of theophylline in syrups: derivative spectroscopy (DS) and partial least-squares regression (PLS), the latter using both artificial and natural calibration sets. HPLC technique was employed to apply a reference method in order to achieve a complete assessment of performance. Calibrations presented excellent analytical figures of merits (i.e. LOD ranged from 0.03 to 0.4 mg L(-1) and analytical sensitivity ranged from 1.7 to 8.3 L mg(-1)). The intermediate precision presented pooled coefficients of variation ranged between 0.54 and 1.08%. Accuracy was studied trough an elliptical joint confidence region test (EJCR) comparing the obtained values when analysing spiked real samples by the HPLC and the studied methodologies. Both studied methods can be considered acceptable for the pharmaceutical quality assurance of theophylline in syrup samples.
Asunto(s)
Broncodilatadores/análisis , Teofilina/análisis , Calibración , Cromatografía Líquida de Alta Presión , Indicadores y Reactivos , Análisis de los Mínimos Cuadrados , Soluciones Farmacéuticas , Reproducibilidad de los Resultados , Espectrofotometría UltravioletaRESUMEN
This work relates the development of an analytical methodology to simultaneously determine three methylxanthines (caffeine, theobromine, and theophylline) in beverages and urine samples based on reversed-phase high-performance liquid chromatography. Separation is made with a Bondesil C18 column using methanol-water-acetic acid or ethanol-water-acetic acid (20:75:5, v/v/v) as the mobile phase at 0.7 mL/min. Identification is made by absorbance detection at 273 nm. Under optimized conditions, the detection limit of the HPLC method is 0.1 pg/mL for all three methylxanthines. This method is applied to urine and to 25 different beverage samples, which included coffee, tea, chocolate, and coconut water. The concentration ranges determined in the beverages and urine are: < 0.1 pg/mL to 350 microg/mL and 3.21 microg/mL to 71.2 microg/mL for caffeine; < 0.1 pg/mL to 32 microg mL and < 0.1 pg/mL to 13.2 microg/mL for theobromine; < 0.1 pg/mL to 47 microg/mL and < 0.1 pg/mL to 66.3 microg/mL for theophylline. The method proposed in this study is rapid and suitable for the simultaneous quantitation of methylxanthines in beverages and human urine samples and requires no extraction step or derivatization.
Asunto(s)
Cafeína/análisis , Cromatografía Líquida de Alta Presión/métodos , Teobromina/análisis , Teofilina/análisis , Bebidas/análisis , Cafeína/orina , Calibración , Sensibilidad y Especificidad , Espectrofotometría Ultravioleta , Teobromina/orina , Teofilina/orinaRESUMEN
Objetivo: investigar la correlación entre los niveles de teofilina en suero y en saliva. Diseño: estudio retrostivo, controlado, dependiente.Sitio: Consulta externa del Servicio de Alergología del Hospital Nacional de Niños de San José, Costa Rica de marzo a noviembre de 1994. Pacientes: 45 niños con diagnóstico previo de asma bronquial tratados con teofilina de acción prolongada por vía oral. Resultados: A cada niño se le tomó una muestra de sangre venosa y otra de saliva después de haber recibido el medicamento por un período mínimo de un mes. Los niveles de broncodilatador en ambos fluídos se cuantificaron por el método de inmunoensayo con fluorescencia y luz polarizada (FPIA). Se analizaron 90 muestras (2 por cada niño) y se obtuvo una correlación (r) de 0.97 (p<0,001). Este estudio demuestra que los niveles de teofilina en saliva proveen una estimación fidedigna de los niveles en sangre, lo que permite un fácil monitoreo a través de la saliva en los niños asmáticos, sin necesidad de la punción venosa
Asunto(s)
Humanos , Masculino , Femenino , Saliva , Teofilina/análisis , Costa RicaRESUMEN
The seeds of Guaraná are rich in xanthines and are used for the preparation of guaraná powder which is very commonly given to horses as a 'tonic' in Brazil. In this paper, the xanthine content of guaraná powder was determined, in addition to its clearance time in horses. Thin-layer chromatography was used as a screening procedure and high-performance liquid chromatography was performed to quantify the drugs in both the powder and urine samples. The guaraná powder was found to contain 2.16, 1.10 and 36.78 mg g-1 of theobromine (TB), theophylline (TP) and caffeine (CF), respectively, and in urine it was possible to detect TB and TP up to 13 d and CF up to 9 d after the administration of guaraná powder.
Asunto(s)
Cafeína/administración & dosificación , Teobromina/administración & dosificación , Teofilina/administración & dosificación , Xantinas/orina , Administración Oral , Animales , Cafeína/análisis , Cafeína/química , Cafeína/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Cromatografía en Capa Delgada/métodos , Combinación de Medicamentos , Caballos , Análisis de Regresión , Reproducibilidad de los Resultados , Semillas , Teobromina/análisis , Teobromina/química , Teobromina/metabolismo , Teofilina/análisis , Teofilina/química , Teofilina/metabolismo , Xantinas/análisisRESUMEN
O Comite Olimpico Internacional propoe medidas para coibir o abuso de cafeina nas atividades esportivas, mas nao faz referencia ao controle de outras metilxantinas estimulantes, como teofilina, teobromina e paraxantina. No presente trabalho foi proposto um metodo para identificar estes farmacos em urina para fins de controle da dopagem. Aliquotas de urina foram submetidas a extracao com cloroformio-isopropanol em meio basico e os extratos analisados por cromatografia em camada delgada e fase gasosa. Na primeira tecnica a separacao foi feita em silicagel G60 com os seguintes sistemas solventes de desenvolvimento: A) acetato de etila-cicloexano-metanol-hidroxido de amonio e acetato de etila-cicloexano-hidroxido de amonio usados sucessivamente e B) cloroformio-acetona-n-butanol-hidroxido de amonio. Foram estabelecidos perfis normais de urina para populacao consumidora de alimentos xantinicos. Para confirmacao de resultados anormais foi utilizada a cromatografia em fase gasosa com detetor de ionizacao de chamas e coluna capilar metilsilicona. A identificacao da cafeina e de produtos de butilacao das dimetilxantinas foi feita pelo indice de retencao de Kovats e retencao relativa
Asunto(s)
Cafeína/análisis , Teobromina/análisis , Teofilina/análisis , Orina/análisis , Cromatografía de Gases , Cromatografía en Capa Delgada , Doping en los DeportesRESUMEN
The types and concentrations of sweeteners in common prescription liquid and chewable medications for pediatric use were determined by manufacturer survey. Oral-liquid and chewable antibiotic, antifungal, bronchodilator, antihistamine, anticonvulsant, and miscellaneous products were identified. The manufactures were asked by telephone the type and amount of sweeteners in their products. Two follow-up letters requested confirmation of the sweetener contents; manufacturers' approval for publication of the information was also requested by mail. Sweetener information on 160 preparations was obtained. For antibiotics such as ampicillin, amoxicillin, erythromycin ethylsuccinate, and penicillin VK, products from different manufacturers had a wide range of sucrose concentration (18%-80%). Only four antibiotic preparations were sucrose free. The bronchodilators and antihistamines contained either sucrose, sorbitol, or saccharin. The anticonvulsants contained 0%-60% sucrose. Health-care practitioners who prescribe or dispense oral liquid or chewable prescription drug products should know that products in a given category can vary in type and amount of sweetener.
Asunto(s)
Preparaciones Farmacéuticas/análisis , Edulcorantes/análisis , Antibacterianos/análisis , Anticonvulsivantes/análisis , Niño , Preescolar , Humanos , Sacarina/análisis , Soluciones , Sacarosa/análisis , Comprimidos , Teofilina/análisisRESUMEN
Tras un análisis un tanto extensivo de los conceptos antiguos y modernos sobre utilización de antihistamínicos como complementos terapéuticos en el tratamiento sintomático del asma, describimos dos series de investigaciones clínicas. Hemos comparado, en pacientes asmáticos, el efecto broncodilatador o preventivo de la bronco-obstrucción producido por el ejercicio físico de un derivado xántico, la oxitrifilina, administrada sola o en asociación a la terfenadina, uno de los antihistamínicos recientemente introducidos en la terapéutica y que no provoca efectos depresivos sobre el sistema nerviosos central. Para comparación se han utilizado los correspondientes grupos testigos a los que se les administró placebo. Los resultados demuestran que cuando la terfenadina se administra con antelación a la oxitrifilina aumenta el efecto broncodilatador de esta substancia y también potencializa el efecto preventivo de la bronco-obstrucción que se produce en los asmáticos sometidos a ejercicio físico. La terfenadina no produjo efectos depresivos ni anticolinérgicos
Asunto(s)
Humanos , Asma/tratamiento farmacológico , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Compuestos de Bencidrilo/uso terapéutico , Colina/análisis , Antagonistas de los Receptores Histamínicos H1/farmacología , Teofilina/análisisRESUMEN
Simultaneous blood and saliva samples were drawn for determination of caffeine and theophylline concentrations in 17 infants receiving caffeine or theophylline therapy for apnea of prematurity. The relationship between serum and saliva concentrations in each drug treatment group was explored using (1) regression analysis and (2) serum:saliva ratio. Significant correlations were observed between serum and salivary concentrations. Salivary concentrations approximated 76 to 80% of the serum concentrations based on the derived serum:saliva ratios. When salivary concentrations were less than 8 microgram/ml, the serum concentrations did not exceed therapeutic range and no clinical toxicity was noted. Monitoring of salivary drug concentrations as an alternative to serum drug concentrations may be useful in preterm infants on methylxanthine therapy. When salivary concentrations exceed 8 microgram/ml, serum concentrations should be determined.