RESUMEN
A quick, simple, sensitive, efficient and stability-indicating reverse-phase ultraperformance liquid chromatographic method for the estimation of propylparaben, methylparaben and sodium benzoate in a pharmaceutical liquid oral formulation was developed. A Waters Acquity UPLC BEH C18, 50 × 2.1 mm, 1.7 µm i.d. column was used to perform chromatographic separation with a 0.1% perchloric acid mobile phase used as solvent A and a mixture of 0.1 % perchloric acid and methanol in the ratio 20:80 (v/v), respectively, as solvent B. The experiments were carried out at a flow rate of 0.4 ml/min and the detection wavelength was 240 nm. The compartment temperature of the column was set at 40°C and the injection volume was set at 2 µl. The main aim of the research was to develop a single UPLC assay method for promethazine (active ingredient) and preservatives in the oral solution of promethazine HCl and dextromethorphan HBr that contains promethazine (active ingredient) and methylparaben, propylparaben and sodium benzoate (preservatives). An assay of dextromethorphan HBr was developed and validated by another HPLC method. The drug and preservatives were eluted at retention times of 19.3 min for promethazine HCl, 9.3 min for methylparaben, 18.9 min for propylparaben and 8.9 min for sodium benzoate. Validation of the developed method was carried out as stated by the International Conference on Harmonization guidelines ICH Q2B and under USP<1225>. The analytical parameters verified specificity/selectivity, linearity, accuracy, ruggedness and robustness. The linearity ranges of promethazine HCL, methylparaben, propylparaben and sodium benzoate were 10-100, 10-80, 1.0-8.0 and 10-80 µg/ml, respectively, with a correlation coefficient of active ingredients and preservatives of 1.00. Percentage recoveries of promethazine, propylparaben, methylparaben, and sodium benzoate were 100.0-100.2, 99.0-100.3, 99.5-98.0 and 99.0-100.0%. The validated analytical method proves that the method is specific, precise, linear, accurate, sensitive, rugged and stable, indicating the quantification of the active ingredient and all preservatives in liquid oral formulations.
Asunto(s)
Antitusígenos , Estabilidad de Medicamentos , Parabenos , Prometazina , Benzoato de Sodio , Parabenos/análisis , Cromatografía Líquida de Alta Presión/métodos , Benzoato de Sodio/análisis , Prometazina/análisis , Reproducibilidad de los Resultados , Modelos Lineales , Antitusígenos/análisis , Antitusígenos/química , Cromatografía de Fase Inversa/métodos , Antagonistas de los Receptores Histamínicos/análisis , Antagonistas de los Receptores Histamínicos/química , Límite de Detección , Administración OralRESUMEN
The investigation of pharmaceuticals as emerging contaminants in marine biota has been insufficient. In this study, we examined the presence of 51 pharmaceuticals in edible oysters along the coasts of the East and South China Seas. Only nine pharmaceuticals were detected. The mean concentrations of all measured pharmaceuticals in oysters per site ranged from 0.804 to 15.1 ng g-1 of dry weight, with antihistamines being the most common. Brompheniramine and promethazine were identified in biota samples for the first time. Although no significant health risks to humans were identified through consumption of oysters, 100-1000 times higher health risks were observed for wildlife like water birds, seasnails, and starfishes. Specifically, sea snails that primarily feed on oysters were found to be at risk of exposure to ciprofloxacin, brompheniramine, and promethazine. These high risks could be attributed to the monotonous diet habits and relatively limited food sources of these organisms. Furthermore, taking chirality into consideration, chlorpheniramine in the oysters was enriched by the S-enantiomer, with a relative potency 1.1-1.3 times higher when chlorpheniramine was considered as a racemate. Overall, this study highlights the prevalence of antihistamines in seafood and underscores the importance of studying enantioselectivities of pharmaceuticals in health risk assessments.
Asunto(s)
Monitoreo del Ambiente , Ostreidae , Preparaciones Farmacéuticas , Contaminantes Químicos del Agua , Animales , Humanos , Bromofeniramina/análisis , China , Clorfeniramina/análisis , Antagonistas de los Receptores Histamínicos/análisis , Océanos y Mares , Ostreidae/química , Preparaciones Farmacéuticas/análisis , Prometazina/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
A simple, sensitive, and effective adsorptive stripping voltammetric sensor for the detection of trace-level promethazine was created based on a gold nanoparticle-graphene nanoplatelet-modified glassy carbon electrode (AuNP-GrNP/GCE). AuNP-GrNP nanocomposites were synthesized using an electroless deposition process, and the morphology was characterized using UV-vis spectroscopy, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The electrochemical behavior and detection of promethazine at the AuNP-GrNP/GCE were investigated utilizing cyclic voltammetry and adsorptive stripping voltammetry. The AuNP-GrNP/GCE showed outstanding synergistic electrochemical activity for promethazine oxidation, a highly active surface area, great adsorptivity, and outstanding catalytic properties. The electrolyte pH, amount of AuNP-GrNP nanocomposite, preconcentration potential (vs. Ag/AgCl), and time were optimized to obtain a high performance electrochemical sensor. Under optimal conditions, the proposed sensor displayed two linear concentration ranges from 1.0 nmol L-1 to 1.0 µmol L-1 and from 1.0 to 10 µmol L-1. The limits of detection and quantitation were 0.40 and 1.4 nmol L-1, respectively. This sensor displayed high sensitivity, a capability for rapid analysis, and excellent repeatability and reproducibility. The developed sensor was effective and practical for promethazine detection in biological fluids and forensic samples, and the obtained results exhibited excellent agreement with the results obtained using the method described in the British Pharmacopoeia. Graphical abstract.
Asunto(s)
Electrodos , Oro/química , Grafito/química , Nanopartículas del Metal/química , Prometazina/análisis , Detección de Abuso de Sustancias/métodos , Líquidos Corporales/química , Humanos , Límite de Detección , Microscopía Electrónica de Rastreo/métodos , Prometazina/normas , Estándares de Referencia , Reproducibilidad de los Resultados , Análisis Espectral/métodosRESUMEN
The innovation of novel and proficient nanostructured materials for the precise level determination of pharmaceuticals in biological fluids is quite crucial to the researchers. With this in mind, we synthesized iron molybdate nanoplates (Fe2(MoO4)3; FeMo NPs) via simple ultrasonic-assisted technique (70 kHz with a power of 100 W). The FeMo NPs were used as the efficient electrocatalyst for electrochemical oxidation of first-generation antihistamine drug- Promethazine hydrochloride (PMH). The as-synthesized FeMo NPs were characterized and confirmed by various characterization techniques such as XRD, Raman, FT-IR, FE-SEM, EDX and Elemental mapping analysis and electron impedance spectroscopy (EIS). In addition, the electrochemical characteristic features of FeMo NPs were scrutinized by electrochemical techniques like cyclic voltammetry (CV) and differential pulse voltammetry technique (DPV). Interestingly, the developed FeMo NPs modified glassy carbon electrode (FeMo NPs/GCE) discloses higher peak current with lesser anodic potential on comparing to bare GCE including wider linear range (0.01-68.65 µM), lower detection limit (0.01 µM) and greater sensitivity (0.97 µAµM-1cm-2). Moreover, the as-synthesized FeMo NPs applied for selectivity, reproducibility, repeatability and storage ability to investigate the practical viability. In the presence of interfering species like cationic, anionic and biological samples, the oxidation peak current response doesn't cause any variation results disclose good selectivity towards the detection of PMH. Additionally, the practical feasibility of the FeMo NPs/GCE was tested by real samples like, commercial tablet (Phenergan 25 mg Tablets) and lake water samples which give satisfactory recovery results. All the above consequences made clear that the proposed sensor FeMo NPs/GCE exhibits excellent electrochemical behavior for electrochemical determination towards oxidation of antihistamine drug PMH.
Asunto(s)
Carbono/química , Electroquímica/instrumentación , Antagonistas de los Receptores Histamínicos/análisis , Hierro/química , Molibdeno/química , Nanoestructuras/química , Prometazina/análisis , Sonicación , Técnicas de Química Sintética , Electrodos , Vidrio/química , Antagonistas de los Receptores Histamínicos/sangre , Antagonistas de los Receptores Histamínicos/orina , Humanos , Concentración de Iones de Hidrógeno , Límite de Detección , Prometazina/sangre , Prometazina/orina , TemperaturaRESUMEN
Paracetamol is an active ingredient commonly found in pharmaceutical formulations in combination with one of the following compounds: codeine, orphenadrine, promethazine, scopolamine, and tramadol. In this work, we propose a unique analytical method for determination of these active ingredients in pharmaceutical samples. The method is based on capillary electrophoresis with capacitively coupled contactless conductivity detection. The separation was achieved on a fused silica capillary (50 cm total length, 40 cm effective length, and 50 µm id) using an optimized background electrolyte composed of 20 mmol/L ß-alanine/4 mmol/L sodium chloride/4 µmol/L sodium hydroxide (pH 9.6). Each sample can be analyzed in a single run (≤2 min) and the limits of detection were 2.5, 0.62, 0.63, 2.5, 15, and 1.6 µmol/L for scopolamine, tramadol, orphenadrine, promethazine, codeine, and paracetamol, respectively. Recovery values for spiked samples were between 94 and 104%.
Asunto(s)
Acetaminofén/análisis , Electroforesis Capilar , Codeína/análisis , Composición de Medicamentos , Orfenadrina/análisis , Prometazina/análisis , Escopolamina/análisis , Tramadol/análisisRESUMEN
In spectral analysis, a chemical component is usually identified by its characteristic spectra, especially the peaks. If two components have overlapping spectral peaks, they are generally considered to be indiscriminate in current analytical chemistry textbooks and related literature. However, if the intensities of the overlapping major spectral peaks are additive, and have different rates of change with respect to variations in the concentration of the individual components, a simple method, named the 'common-origin ray', for the simultaneous determination of two components can be established. Several case studies highlighting its applications are presented.
Asunto(s)
Dispersión Dinámica de Luz/métodos , Procesamiento de Señales Asistido por Computador , Espectrometría de Fluorescencia/métodos , Espectrofotometría Ultravioleta/métodos , Cerio/análisis , Clorpromazina/análisis , Europio/análisis , Isomerismo , Modelos Teóricos , Naftoles/análisis , Naftoles/química , Fenilalanina/análisis , Fenilalanina/química , Prometazina/análisis , Puntos Cuánticos , Triptófano/análisis , Triptófano/química , beta-Ciclodextrinas/químicaRESUMEN
Quantitative matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) approaches have historically suffered from poor accuracy and precision mainly due to the nonuniform distribution of matrix and analyte across the target surface, matrix interferences, and ionization suppression. Tandem mass spectrometry (MS/MS) can be used to ensure chemical specificity as well as improve signal-to-noise ratios by eliminating interferences from chemical noise, alleviating some concerns about dynamic range. However, conventional MALDI TOF/TOF modalities typically only scan for a single MS/MS event per laser shot, and multiplex assays require sequential analyses. We describe here new methodology that allows for multiple TOF/TOF fragmentation events to be performed in a single laser shot. This technology allows the reference of analyte intensity to that of the internal standard in each laser shot, even when the analyte and internal standard are quite disparate in m/z, thereby improving quantification while maintaining chemical specificity and duty cycle. In the quantitative analysis of the drug enalapril in pooled human plasma with ramipril as an internal standard, a greater than 4-fold improvement in relative standard deviation (<10%) was observed as well as improved coefficients of determination (R2) and accuracy (>85% quality controls). Using this approach we have also performed simultaneous quantitative analysis of three drugs (promethazine, enalapril, and verapamil) using deuterated analogues of these drugs as internal standards.
Asunto(s)
Antihipertensivos/análisis , Enalapril/análisis , Rayos Láser , Prometazina/análisis , Verapamilo/análisis , Humanos , Estructura Molecular , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Factores de TiempoRESUMEN
The banned addition of psychiatric drugs such as phenothiazines to animal feed and foodstuffs increases the risk of human organ lesion. Phenothiazines usually exhibit weak native fluorescence and can be oxidized to strongly fluorescent compounds. In this study, a novel, sensitive and convenient method of HPLC-fluorescence detection based on post-column on-line oxidizing with lead dioxide solid-phase reactor has been developed for simultaneous determination of three banned psychotropic drugs, promethazine, chlorpromazine and thioridazine. Three compounds were successfully separated on an Agilent TC-C18 column with mobile phase of acetonitrile (A) and water (B), both containing 0.5% (v/v) formic acid. A gradient elution was programmed and fluorimetric detection was performed at λex /λem of 332/373 nm for promethazine, 340/380 nm for chlorpromazine and 352/432 nm for thioridazine. The calibration graphs gave good linearity over the concentration ranges of 30.0-4976.4 µg/L for promethazine, 2.0-2153.2 µg/L for chlorpromazine, and 15.0-3088.0 µg/L for thioridazine, and correlation coefficients (r) were ≥0.995. The method was applied to the determination of phenothiazines in pig feed and pig tissue, and the average spiked recoveries were in the range 69.1-115.4%.
Asunto(s)
Alimentación Animal/análisis , Cromatografía Líquida de Alta Presión/métodos , Psicotrópicos/análisis , Sus scrofa , Animales , Calibración , Clorpromazina/análisis , Cromatografía Líquida de Alta Presión/instrumentación , Fluorescencia , Análisis de los Alimentos/métodos , Contaminación de Alimentos/análisis , Riñón/química , Oxidación-Reducción , Prometazina/análisis , Sensibilidad y Especificidad , Temperatura , Tioridazina/análisisRESUMEN
Forensic toxicological drug analyses of human specimens are usually performed immediately after autopsy or on frozen preserved tissues. Occasionally, cases require analysis of drugs from tissues fixed in formalin solution. To improve the estimation of the level of drug in tissues following formalin fixation, we studied drug concentrations in human tissues, liver and kidney, that were collected from a drug-positive autopsy case. Parts of tissues were preserved in formalin solution for 1, 3, 6 and 13 months. Tissues obtained before and after preservation, along with tissue-exposed fixatives, were assayed using gas chromatography-mass spectrometry; all of the samples were assayed for the presence of drugs and changes in the drug concentrations both before and after preservation in formalin. Concentrations of assayed drugs decreased upon fixation in formalin; levels of these drugs did not necessarily show further decreases during subsequent storage in fixative, up to 13 months. Distinct trends in drug levels were found in liver and kidney. In liver, the levels of chlorpromazine, levomepromazine, and promethazine decreased to 23-39% at 1 month after preservation; all 3 of these drugs were detected at all tested time points of preservation. Bromazepam was not detected at 13 months after preservation. Milnacipran was the most unstable after preservation in formalin solution among all of the assayed drugs. In kidney, all assayed drugs exhibited reduced stability during preservation compared to levels in liver. Methamphetamine and methylenedioxymethamphetamine were not detected in any time points of tissues. The proportions of the drugs that remained within the tissues differed between liver and kidney. Also, S-oxide compounds of chlorpromazine and levomepromazine, which were not observed before preservation, were detected in fixed liver tissues and their fixatives at 3, 6 and 13 months of preservation. These results suggest that analyses in formalin-fixed tissues need to include analysis of various organ-tissues and their fixatives at multiple time points for the duration of preservation. These analyses should include detection of chemical degradation/denaturation products, such as S-oxides of chlorpromazine and levomepromazine.
Asunto(s)
Antipsicóticos/análisis , Fijadores , Formaldehído , Riñón/química , Hígado/química , Narcóticos/análisis , Preservación de Órganos/métodos , Adulto , Bromazepam/análisis , Clorpromazina/análisis , Ciclopropanos/análisis , Estabilidad de Medicamentos , Toxicología Forense , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Metanfetamina/análisis , Metotrimeprazina/análisis , Milnaciprán , N-Metil-3,4-metilenodioxianfetamina/análisis , Prometazina/análisis , Factores de TiempoRESUMEN
We report the quantification of promethazine (PMZ) using glassy carbon electrodes (GCE) modified with bamboo-like multi-walled carbon nanotubes (bCNT) dispersed in double stranded calf-thymus DNA (dsDNA) (GCE/bCNT-dsDNA). Cyclic voltammetry measurements demonstrated that PMZ presents a thin film-confined redox behavior at GCE/bCNT-dsDNA, opposite to the irreversibly-adsorbed behavior obtained at GCE modified with bCNT dispersed in ethanol (GCE/bCNT). Differential pulse voltammetry-adsorptive stripping with medium exchange experiments performed with GCE/bCNT-dsDNA and GCE modified with bCNTs dispersed in single-stranded calf-thymus DNA (ssDNA) confirmed that the interaction between PMZ and bCNT-dsDNA is mainly hydrophobic. These differences are due to the intercalation of PMZ within the dsDNA that supports the bCNTs, as evidenced from the bathochromic displacement of UV-Vis absorption spectra of PMZ and quantum dynamics calculations at DFTB level. The efficient accumulation of PMZ at GCE/bCNT-dsDNA made possible its sensitive quantification at nanomolar levels (sensitivity: (3.50±0.05)×10(8) µA·cm(-2)·M(-1) and detection limit: 23 nM). The biosensor was successfully used for the determination of PMZ in a pharmaceutical product with excellent correlation.
Asunto(s)
Antialérgicos/análisis , Técnicas Biosensibles/instrumentación , ADN/química , Nanotubos de Carbono/química , Prometazina/análisis , Animales , Bovinos , Técnicas Electroquímicas/instrumentación , Electrodos , Diseño de Equipo , Límite de Detección , Modelos MolecularesRESUMEN
This paper reports the establishment of a method for rapid identification 15 effective components of anti common cold medicine (paracetamol, aminophenazone, pseudoephedrine hydrochloride, methylephedrine hydrochloride, caffeine, amantadine hydrochloride, phenazone, guaifenesin, chlorphenamine maleate, dextromethorphen hydrobromide, diphenhydramine hydrochloride, promethazine hydrochloride, propyphenazone, benorilate and diclofenac sodium) with MRM by LC-MS/MS. The samples were extracted by methanol and were separated from a Altantis T3 column within 15 min with a gradient of acetonitrile-ammonium acetate (containing 0.25% glacial acetic acid), a tandem quadrupole mass spectrometer equipped with electrospray ionization source (ESI) was used in positive ion mode, and multiple reaction monitoring (MRM) was performed for qualitative analysis of these compounds. The minimum detectable quantity were 0.33-2.5 microg x kg(-1) of the 15 compounds. The method is simple, accurate and with good reproducibility for rapid identification many components in the same chromatographic condition, and provides a reference for qualitative analysis illegally added chemicals in anti common cold medicine.
Asunto(s)
Antiinflamatorios no Esteroideos/análisis , Antipiréticos/análisis , Acetaminofén/análisis , Acetanilidas/análisis , Amantadina/análisis , Aminopirina/análisis , Antipirina/análogos & derivados , Antipirina/análisis , Cafeína/análisis , Clorfeniramina/análisis , Cromatografía Liquida , Diclofenaco/análisis , Difenhidramina/análisis , Contaminación de Medicamentos , Estabilidad de Medicamentos , Efedrina/análogos & derivados , Efedrina/análisis , Guaifenesina/análisis , Prometazina/análisis , Seudoefedrina/análisis , Reproducibilidad de los Resultados , Salicilatos/análisis , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en TándemRESUMEN
Conditions for determination of: ketotifen hydrogen fumarate, azelastine hydrochloride, dimetindene maleate and promethazine hydrochloride by densitometric method in substances and pharmaceuticals were provided. Maximum wavelenghts were: 228 nm for ketotifen hydrogen fumarate, 295 nm for azelastine hydrochloride, 265 nm for dimetindene maleate and 255 nm for promethazine hydrochloride. The limits of quantification were in the ranges of 0.2-5 microg/spot. The statistical data showed adequate accuracy and precision of developed methods.
Asunto(s)
Cromatografía en Capa Delgada , Densitometría , Dimetindeno/análisis , Antagonistas de los Receptores Histamínicos H1/análisis , Ftalazinas/análisis , Prometazina/análisis , Calibración , Cromatografía en Capa Delgada/normas , Densitometría/normas , Cetotifen/análisis , Límite de Detección , Análisis de Regresión , Reproducibilidad de los ResultadosRESUMEN
Based on the phenomenon that each of chlorpromazine (CPZ), promethazine (PMZ), chlorpromazine sulfoxide (CPZSO) and promethazine sulfoxide (PMZSO) could enhance the electrochemiluminescence (ECL) intensity of tris(2,2'-bipyridyl) ruthenium, a novel and sensitive method was proposed for the simultaneous determination of CPZ, PMZ and their main metabolites using capillary electrophoresis (CE) coupled with ECL detection. The influences of several experimental parameters were explored. The optimum experimental conditions were as follows: detection potential of 1. 20 V (Ag/AgCl), 40 mmol/L of phosphate buffer solution (pH 6.5) containing 5 mmol/L tris(2,2'-bipyridyl) ruthenium in ECL detection cell, running buffer solution of 18 mmol/L (pH 4.8), sample injection of 8 s at 11 kV, and separation voltage of 13.5 kV. The detection limits (3sigma) of this method were 8.3 x 10(-7) g/L for CPZ, 7.2 x 10(-6) g/L for PMZ, 1.9 x 10(-5) g/L for CPZSO and 3.7 x 10(-6) g/L for PMZSO. The linear ranges of ECL intensity versus mass concentration of medicaments were 7. 1 x 10(-6) - 6. 3 x 10(-3) g/L for CPZ, 7.5 x 10(-5) - 4.6 x 10(-3) g/L for PMZ, 9.7 x 10(-5) - 3.6 x 10(-3) g/L for CPZSO and 8.1 x 10(-5) - 7.7 x 10(-3) g/L for PMZSO. The relative standard deviations (RSDs) of the four target compounds were not more than 3% for ECL intensity and 1% for migration time. This method has the merits of simplicity, speediness, sensitivity, small sample injection, and free from interference. This method was successfully utilized to directly and simultaneously detect CPZ, PMZ, CPZSO and PMZSO in urine samples of pet dogs.
Asunto(s)
Clorpromazina/análisis , Técnicas Electroquímicas/métodos , Electroforesis Capilar/métodos , Luminiscencia , Prometazina/análisis , Animales , Clorpromazina/análogos & derivados , Clorpromazina/metabolismo , Clorpromazina/orina , Perros , Prometazina/análogos & derivados , Prometazina/metabolismo , Prometazina/orinaRESUMEN
A simple and sensitive method is described for voltammetric determination of promethazine hydrochloride (PMZ), a widely used phenothiazine drug, based on its electrochemical oxidation at a multi-wall carbon nanotube (MWCNT) modified glassy carbon electrode (GCE). Compared with bare GCE, the MWCNT-modified GCE exhibited excellent enhancement effect on the electrochemical oxidation of PMZ. PMZ yielded two anodic peaks at about 0.61 V and 0.78 V, and the peak at 0.61 V was applied to the determination. Under optimized conditions, the anodic peak current was linear to the concentration of PMZ in the range from 5.0 × 10(-8) to 4.0 × 10(-4) M with the detection limit of 1.0 × 10(-8) M. The relative standard deviation (RSD) was 2.28% for 8.0 × 10(-6) M PMZ (n = 10). To further validate its possible application, the proposed method was successfully used for the quantification of PMZ in pharmaceutical formulations and biological fluids with satisfactory results.
Asunto(s)
Antialérgicos/análisis , Técnicas Electroquímicas/métodos , Nanotubos de Carbono/química , Preparaciones Farmacéuticas/química , Prometazina/análisis , Antialérgicos/sangre , Antialérgicos/orina , Electrodos , Humanos , Límite de Detección , Oxidación-Reducción , Prometazina/sangre , Prometazina/orina , Sensibilidad y EspecificidadRESUMEN
In pH 1.0 HCl medium, 12-tungstophosphoric acid (TP) reacted with promethazine hydrochloride (PMZ) and chlorpromazine hydrochloride (CPZ) to form ion-association complexes, which led to a great enhancement of the resonance nonlinear scattering such as second-order scattering (SOS) and frequency doubling scattering (FDS). Their maximum SOS and FDS peaks were located at 585 nm (TP-PMZ), 584 nm (TP-CPZ) and 388 nm (TP-PMZ), 329 nm (TP-CPZ), respectively. These results provided some indication for the determination of PMZ and CPZ by SOS and FDS methods. The linear range of TP-PMZ and TP-CPZ systems were 0.0069-2.5 microg mL(-1), 0.102-5.0 microg mL(-1) (SOS) and 0.079-6.0 microg mL(-1), 0.0133-5.0 microg mL(-1) (FDS), respectively. The detection limits (3sigma) of PMZ and CPZ were 2.08 ng mL(-1), 3.07 ng mL(-1) (SOS) and 2.22 ng mL(-1), 3.98 ng mL(-1) (FDS), respectively. In this work, the optimum reaction conditions, the influences of coexisting substances and ionic strength and analytical application have been investigated. The methods have been successfully applied to the determination of PMZ and CPZ in tablets. In addition, the composition of ion-association complexes and the reaction mechanism are also discussed.
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Clorpromazina/análisis , Clorpromazina/química , Dinámicas no Lineales , Ácidos Fosfóricos/química , Prometazina/análisis , Prometazina/química , Dispersión de Radiación , Compuestos de Tungsteno/química , Ácidos/química , Iones , Concentración Osmolar , Análisis Espectral , ComprimidosRESUMEN
A simultaneous electrochemiluminescence (ECL) and electrochemical (EC) detection scheme for NACE was presented for fast analysis of tertiary amines. Both ECL and EC signals were generated at the same Pt electrode. Triethylamine (TEA), tripropylamine (TPrA), chlorpromazine, promethazine, and dioxopromethazine (DPZ) were selected to validate NACE-ECL/EC dual detection strategy. The linear ranges for TEA and TPrA were 0.01-500 and 0.01-10 microM with the detection limits of 8.0 and 5.0 nM (S/N=3), respectively. The RSDs (n=6) of the migration time and the ECL intensity for 1 microM TEA and 0.5 microM TPrA were 0.1 and 2.8%, and 0.2 and 1.8% with theoretical plate numbers of 180,000 and 700,000 per meter, respectively. These two analytes could be separated within 92 s and the Pt electrode did not need reactivation during the experiments. Chlorpromazine, promethazine, and DPZ could be well separated by NACE. The proposed method was also demonstrated for fast determination of DPZ in human urine with simple sample preparation. The results indicated that NACE-ECL/EC had the advantages of simple and fast analysis with more information, wide linear range, high sensitivity, and compatibility with real urine sample.
Asunto(s)
Aminas/análisis , Electroquímica/métodos , Mediciones Luminiscentes/métodos , Aminas/orina , Clorpromazina/análisis , Electroforesis Capilar/métodos , Electroforesis por Microchip , Etilaminas/análisis , Humanos , Mediciones Luminiscentes/instrumentación , Prometazina/análogos & derivados , Prometazina/análisis , Propilaminas/análisisRESUMEN
A simple, rapid, and validated method for separation and determination of promethazine enantiomers was developed. Promethazine was separated and quantitated on a Vancomycin Chirobiotic V column (250 x 4.6 mm), using a mixture of methanol, acetic acid, and triethylamine (100:0.1:0.1%, by volume) as a mobile phase at 20 degrees C and at a flow rate of 1 mL/min. The UV-detector was set to 254 nm. Acetyl salicylic acid (Aspirin) was used as an internal standard. The applied HPLC method allowed separation and quantification of promethazine enantiomers with good linearity (r > .999) in the studied range. The relative standard deviations (RSD) were 0.29 and 0.36 for the promethazine enantiomers with accuracy of 100.06 and 100.08. The limit of detection and limit of quantification of promethazine enantiomers were found to be 0.04 and 0.07 microg/mL, respectively. The method was validated through the parameters of linearity, accuracy, precision, and robustness. The HPLC method was applied for the quantitative determination of promethazine in pharmaceutical formulations.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Antagonistas de los Receptores Histamínicos H1/análisis , Prometazina/análisis , Formas de Dosificación , Reproducibilidad de los Resultados , EstereoisomerismoRESUMEN
A simple and rapid stability-indicating HPLC method was developed for determination of promethazine hydrochloride (PMZ) in hot-melt extruded (HME) films and sustained release tablets. Chromatographic separation was achieved on a 150 mm x 4.6 mm i.d., 3 microm particle size, C8 (2) column with acetonitrile-25mM phosphate buffer (pH 7.0), 50:50 (v/v) as mobile phase at a flow rate of 1 mL min(-1). Quantitation was achieved with UV detection at 249 nm based on peak area. The method was validated in terms of linearity, precision, accuracy, robustness specificity, limits of detection and quantitation according to ICH guidelines. Specificity was validated by subjecting the drug to acid, base, oxidative, reductive and dry heat degradations. None of the degradation products obtained by forced degradation interfered with the PMZ peak. The method was successfully applied for assessing the stability of the drug in the HME films and sustained release tablet formulations. In addition, uniformity of PMZ content in HME films was also determined using the method developed. Excipients present in either of the dosage forms analyzed did not interfere with the analysis indicating the specificity of the method. Due to its simplicity and accuracy, the method is suitable for application to various dosage forms.
Asunto(s)
Antagonistas de los Receptores Histamínicos H1/análisis , Prometazina/análisis , Cromatografía Líquida de Alta Presión , Formas de Dosificación , Calor , Concentración de Iones de Hidrógeno , Hidrólisis , Oxidación-Reducción , Estándares de Referencia , Reproducibilidad de los Resultados , Solubilidad , Espectrofotometría UltravioletaRESUMEN
Herein, quantitative online monitoring of concentration fluctuations of different interesting drugs, namely, the phenothiazine promethazine as well as the anti-cancer agent mitoxantrone via surface enhanced Raman scattering assay based on a microfluidic device is demonstrated. With the applied liquid/liquid two-phase-segmented flow system we succeed in preventing the adhesion of nanoparticle aggregates to the channel walls which is necessary for a quantitative analysis. Even after repeated cycles no carry-over due to sedimentation of colloid particles is observed. To the best of our knowledge these are the first measurements applying a combination of a microfluidic device with SERS detection for quantitative online monitoring of fluctuations in drug concentrations over hours without use of aggressive chemicals for rinsing the chip surfaces prior to each measurement.
Asunto(s)
Química Farmacéutica/métodos , Técnicas Analíticas Microfluídicas , Microfluídica/métodos , Preparaciones Farmacéuticas/análisis , Espectrometría Raman/métodos , Coloides/análisis , Microquímica/métodos , Microfluídica/instrumentación , Mitoxantrona/análisis , Modelos Químicos , Conformación Molecular , Prometazina/análisis , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Programas Informáticos , Espectrofotometría Ultravioleta/métodosRESUMEN
Over the past several years, Medical Examiners in Kentucky and around the nation have observed a dramatic rise in drug intoxication deaths involving the prescription medication methadone. This documented rise in methadone-related deaths requires a better understanding of methadone's pathophysiology and the ways it contributes to significantly increase morbidity and mortality. This study reviews 176 fatalities ascribed to methadone toxicity by the Office of the Chief Medical Examiner in Kentucky between 2000 and 2004. Postmortem toxicological analysis recorded a more than 10-fold increase in methadone toxicity fatalities, rising from 6 cases in 2000 to 68 cases in 2003. Of the 176 methadone-related fatalities, methadone was the only drug detected in postmortem blood and urine toxicological analyses in 11 (6.25%) cases. The mean methadone blood concentration of all 176 cases was 0.535 mg / L (0.02-4.0). The following psychoactive medications were detected: antidepressants (39.8%), benzodiazepines (32.4%), and other opioids in addition to methadone (27.8%). Cannabinoids were detected in 44 (28.4%) cases and cocaine or metabolite in 34 (21.9%) cases. Of the 95 cases with a known history of methadone use, 46 (48.4%) involved prescription by private physician. The interpretation of blood methadone concentrations alone or combined with other psychoactive drugs requires consideration of the subject's potential chronic use of and tolerance to the drug. A thorough investigation into the practices of procurement and use/abuse of methadone is essential to arrive at the proper designation of the cause of death.