RESUMEN
Vancomycin and teicoplanin are glycopeptide antibacterials that inhibit the bacteria cell wall synthesis showing activity against gram-positive bacteria. Development of the sensitive method is of great importance for quality control of these drugs that are fermentation products. Modification of the fermentation conditions could cause the differences in the relative amount of the total substance or component, as it is the case with teicoplanin. The main objective of this study was development of the sensitive and effective ultra high performance liquid chromatography - tandem mass sprectrometry (UHPLC-MS/MS) method for simultaneous quantification of vancomycin, all six subcomponents of teicoplanin, and its pharmacopoeial impurity A in pharmaceutical forms. The scientific-based Quality by Design approach was implemented in the MS and UHPLC method development. Detection and quantification of analytes were carried out in positive electrospray ion mode by multiple reaction monitoring. Capillary voltage, cone voltage and collision energy were optimized by implementing experimental design methodology and optimal values for each fragment ion were obtained by performing experiments according to 'Rechtschaffen' design matrix. An ACQUITY CSH Phenyl-hexyl (2.1 × 50 mm, particle size 1.7 µm) column was chosen for the separation under the gradient elution mode with the mobile phase consisted of 0.1% formic acid in water (mobile phase A) and acetonitrile (mobile phase B). Optimal gradient elution parameters were achieved by applying 'Rechtschaffen' design too. Method operable design regions were constructed for investigated MS and chromatographic parameters. The method was fully validated, and its applicability was confirmed throughout the ability to follow the behavior of vancomycin and teicoplanin under stress conditions.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Glicopéptidos/análisis , Espectrometría de Masas en Tándem/métodos , Formas de Dosificación , Límite de Detección , Modelos Lineales , Control de Calidad , Reproducibilidad de los ResultadosRESUMEN
In this paper, the mass spectrometry (MS) detection has been applied for screening of fosinopril sodium impurities which arise during forced stress study. Before MS analysis, liquid chromatographic method with suitable mobile phase composition was developed. The separation was done on SunFire 100 mm x 4.6 mm 3.5 microm particle size column. The mobile phases which consisted of methanol-ammonium acetate buffer-acetic acid, in different ratios, were used in a preliminary study. Flow rate was 0.3 mL min(-1). Under these conditions, percent of methanol, concentration of ammonium acetate buffer and acetic acid content were tested simultaneously applying central composite design (CCD) and artificial neural network (ANN). The combinations of experimental design (ED) and ANN present powerful technique in method optimization. Input and output variables from CCD were used for network training, verification and testing. Multiple layer perceptron (MLP) with back propagation (BP) algorithm was chosen for network training. When the optimal neural topology was selected, network was trained by adjusting strength of connections between neurons in order to adapt the outputs of whole network to be closer to the desired outputs, or to minimize the sum of the squared errors. From the method optimization the following mobile phase composition was selected as appropriate: methanol-10 mM ammonium acetate buffer-acidic acid (80:19.5:0.5 v/v/v). This mobile phase was used as inlet for MS. According to molecular structure and literature data, electrospray positive ion mode was applied for analysis of fosinopril sodium and its impurities. The proposed method could be used for screening of fosinopril sodium impurities in bulk and pharmaceuticals, as well as for tracking the degradation under stress conditions.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Fosinopril/análisis , Espectrometría de Masa por Ionización de Electrospray/métodos , Fosinopril/química , Estructura MolecularRESUMEN
Perindopril tert-butylamine is a new member of angiotensin-converting enzyme inhibitors group used in the treatment of hypertension and heart failure. In this paper, the evaluation of reversed-phase high-performance liquid chromatographic method (RP-HPLC) for the determination of impurities level of perindopril tert-butylamine in tablets was done. The chromatograms were recorded using a Hewlett Packard 1100 chromatographic system with DAD detector. Separations were performed on a YMC-Pack C8 column (250 mm x 4.6mm; 5 microm particle size) at 50 degrees C column temperature. Mobile phase was a mixture of acetonitrile-potassium phosphate buffer (0.05 M) (37:63, v/v) (pH 2.5). pH of the mobile phase was adjusted with ortophosphoric acid. Mixture of acetonitrile-water (40:60, v/v) was used as a solvent. Injection volume was 50 microl, flow rate 1.7 ml min(-1) and UV-detection was performed at 215 nm. The developed method subjected to method validation and parameters in terms of selectivity, linearity, precision, accuracy, limit of detection, limit of quantitation and robustness were defined. The validated method is suitable for the simultaneous determination of perindopril tert-butylamine as well as its impurities in pharmaceuticals.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/análisis , Cromatografía Líquida de Alta Presión/métodos , Perindopril/análisis , Preparaciones Farmacéuticas/análisis , Tecnología Farmacéutica/métodos , Acetonitrilos/química , Inhibidores de la Enzima Convertidora de Angiotensina/química , Tampones (Química) , Calibración , Contaminación de Medicamentos/prevención & control , Concentración de Iones de Hidrógeno , Estructura Molecular , Perindopril/química , Preparaciones Farmacéuticas/química , Fosfatos/química , Compuestos de Potasio/química , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Soluciones/química , Espectrofotometría Ultravioleta , Comprimidos , TemperaturaRESUMEN
Twenty-one patients with tumor stage mycosis fungoides (MF) with or without lymph node (LN) involvement, were treated with total skin electron beam irradiation (TSEB) followed by six monthly cycles of systemic chemotherapy (CT) of either mechlorethamine (HN2) or cyclophosphamide (CTX) with vincristine (VCR), procarbazine, and prednisone (PRD) (COPP or MOPP). All patients had complete clearing of the skin after TSEB. However, while receiving chemotherapy, two patients developed visceral involvement and eight patients relapsed with limited cutaneous plaques (LCP). The median duration of remission was 12 months from the completion of TSEB, and all patients relapsed with cutaneous plaques within 25 months. Complete remission was again achieved using additional electron irradiation and maintenance therapy in all but one patient. Multiple cutaneous recurrences occurred in all patients. Median survival from the initiation of TSEB is 6 years. Five patients are living beyond 8 years (four off treatment without disease for 1 to 7 years). LN involvement did not influence initial response or survival. Combined modality therapy for tumor stage MF using TSEB followed by systemic CT and subsequent maintenance therapy may lead eventually to prolonged disease-free survival (DFS) in selected patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Micosis Fungoide/tratamiento farmacológico , Micosis Fungoide/radioterapia , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/radioterapia , Adulto , Anciano , Terapia Combinada , Ciclofosfamida/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Mecloretamina/administración & dosificación , Persona de Mediana Edad , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Pronóstico , Inducción de Remisión , Vincristina/administración & dosificaciónRESUMEN
Fosinopril sodium presents a prodrug for the active angiotensin converting enzyme (ACE) inhibitor, fosinoprilat. The dual elimination of fosinoprilat by the liver and the kidney distinguishes fosinopril from other angiotensin converting enzyme inhibitors. Such ways of elimination are important for antihypertensive therapy of patients on haemodialysis. The paper presents development and evaluation of a new and sensitive liquid chromatographic (LC) method for the analysis of fosinoprilat in plasma obtained from patients on haemodialysis. A microemulsion system mixture as mobile phase has been used for the separation and analysis of fosinoprilat in plasma samples. The plasma samples were injected directly onto the HPLC system (Waters Breeze) after appropriate sample dilution with mobile phase. Separations were performed on the Bakerbond ENV 4.6 mm x 150 mm, 5 microm particle size column with UV detection at 220 nm. The flow rate was 1.00 mL min(-1). The mobile phase consisted of 1.0% (w/v) of diisopropyl ether, 2.0% (w/v) of sodium dodecyl sulphate (SDS), 6.0% (w/v) of n-propanol and 91% (w/v) of aqueous 25 mM di-sodium hydrogen phosphate, pH adjusted to 2.8 with 85% orthophosphoric acid. The developed method was then subjected to method validation according to the criteria stated in the FDA bioanalytical method validation guidance. The results for specificity, linearity, low limit of quantification (LLOQ), precision, accuracy and stability were within the accepted criteria. The unique approach applied in this paper makes possible the determination of fosinoprilat even in the presence of metabolites of other drugs, so the method can be used for obtaining the reliable results in a fast and simple way.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/sangre , Cromatografía Líquida de Alta Presión/métodos , Fosinopril/análogos & derivados , Calibración , Emulsiones , Fosinopril/sangre , Humanos , Diálisis Renal , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrofotometría UltravioletaRESUMEN
The simple and rapid RP-HPLC method, for the simultaneous determination of lidocaine and cetrimonium bromide in the presence of pellet color corrigent, was developed. Separations were performed on a Beckman Ultrasphere ODS 4.6 mm x 15 cm, 5 microm particle column at 40 degrees C. The mobile phase consisted of water phase and acetonitrile (72:28 V/V), pH value of the mobile phase was adjusted to 2.0 with 85% ortophosphoric acid. Bisacodil was used as an internal standard. The flow rate was 1 ml/min and UV detection was performed at 208 nm. The proposed RP-HPLC method was validated and all the parameters for the validation of the method are given. According to the obtained results, the developed method was found to be suitable and accurate for the determination of these drugs in commercial formulations.
Asunto(s)
Compuestos de Cetrimonio/análisis , Cromatografía Líquida de Alta Presión/métodos , Lidocaína/análisis , Acetonitrilos/química , Cetrimonio , Concentración de Iones de Hidrógeno , Indicadores y Reactivos , Preparaciones Farmacéuticas , Reproducibilidad de los Resultados , TemperaturaRESUMEN
A patient with generalized granuloma annulare experienced resolution of her lesions after six months of treatment with 1,500 mg/day of niacinamide. Niacinamide seems to be a reasonably safe drug that, even at relatively high doses, is associated with a low incidence of side effects. The participation of a delayed hypersensitivity reaction in the pathogenesis of granuloma annulare and possible mechanisms involving niacinamide in this type of reaction are discussed.
Asunto(s)
Granuloma/tratamiento farmacológico , Niacinamida/administración & dosificación , Enfermedades de la Piel/tratamiento farmacológico , Femenino , Granuloma/etiología , Granuloma/patología , Humanos , Hipersensibilidad Tardía/complicaciones , Persona de Mediana Edad , Enfermedades de la Piel/etiología , Enfermedades de la Piel/patologíaRESUMEN
A 68-year-old man had a solitary, eczematiform lesion of two years' duration on the digital dorsal surface of his right foot. Despite its innocuous appearance, the lesion showed histologic characteristics of advanced, plaque-type mycosis fungoides. The patient's clinically benign yet histologically malignant disease manifestation is discussed. The distinction between localized mycosis fungoides and Woringer-Kolopp disease is also reviewed.
Asunto(s)
Enfermedades del Pie/diagnóstico , Micosis Fungoide/diagnóstico , Anciano , Biopsia , Diagnóstico Diferencial , Eccema/diagnóstico , Enfermedades del Pie/patología , Humanos , Masculino , Micosis Fungoide/patología , Piel/patología , Enfermedades de la Piel/diagnósticoRESUMEN
Histopathologic and ultrastructural observations in a case of Pagetoid reticulosis (Woringer and Kolopp disease) are reported. The most important clinical feature of this disease is manifestation as a single very slowly enlarging verrucoid, plaque-type skin lesion without internal organ involvement. Histologically, the epidermis is extremely acanthotic and densely infiltrated with numerous atypical appearing cells that are entirely absent from the dermis, which simply contains a banal dense chronic inflammatory infiltrate. Ultrastructural study showed that there are two major types of unusual cells infiltrating the epidermis. One type is a large lymphoid cell similar to the stimulated lymphocyte. The second type differs from the first in having paler staining of the nucleus and cytoplasm and showing cell membrane damage. These cells probably derive by degeneration from the large lymphoid cells. The presence of transitional forms favors this interpretation. Occasionally, degeneration of these cells proceeds to their complete necrosis.
Asunto(s)
Enfermedades Linfáticas/patología , Neoplasias Cutáneas/ultraestructura , Anciano , Humanos , Masculino , Piel/ultraestructuraRESUMEN
American leishmaniasis that is acquired in Panama may appear clinically as a sporotrichoid eruption. When leisons reminiscent of sporotrichosis are encountered, a careful history of the patient's travels should be made, as well as a search for the organism of leischmaniasis in tissue smears, histopathological sections, and cultured media. We report the case of an American soldier stationed in Panama who had developed an ulcer on the dorsum of his right wrist, and nodules on his right forearm that were arranged in a linear pattern. The initial clinical impression was that of sporotrichosis, but on careful study of the patient's history, and after other appropriate investigations were made, it was discovered that the patient had leishmaniasis.
Asunto(s)
Leishmaniasis/diagnóstico , Esporotricosis/diagnóstico , Adulto , Gluconato de Sodio Antimonio/efectos adversos , Gluconato de Sodio Antimonio/uso terapéutico , Diagnóstico Diferencial , Electrocardiografía , Eritromicina/uso terapéutico , Corazón/efectos de los fármacos , Humanos , Leishmaniasis/tratamiento farmacológico , MasculinoRESUMEN
A subcorneal pustular dermatosis and a vesicobullous eruption with the clinical ad histologic features of localized bullous pemphigoid(BP) were observed in a 44-year-old woman with morphea and a recent history of phenytoin sodium-induced toxic epidermal necrolysis. Localized BP is rare and has been previously described in association with other cutaneous disorders. The coexistence of localized BP, morphea, and subcorneal pustulosis suggests that immunologic factors may play a role in all three conditions.
Asunto(s)
Penfigoide Ampolloso/complicaciones , Esclerodermia Localizada/complicaciones , Enfermedades Cutáneas Vesiculoampollosas/complicaciones , Adulto , Femenino , Humanos , Penfigoide Ampolloso/patología , Esclerodermia Localizada/patología , Piel/patología , Enfermedades de la Piel/complicaciones , Enfermedades de la Piel/patología , Síndrome de Stevens-Johnson/complicaciones , SupuraciónRESUMEN
Bullous eruption of diabetes is a cutaneous sign of diabetes mellitus. Patients with this disorder manifest a sudden onset of intraepidermal or subepidermal bullae, which are primarily confined to the extremities and heal within several weeks without scarring. Our patient had severe diabetes and experienced two episodes of bullae associated with intense, ultraviolet light exposure. Negative immunofluorescence, early disappearance of anchoring filaments and half-desmosomes between cell membrane and basal lamina, and the absence of urinary uroporphyrins separate this entity from certain similar-appearing conditions. Cation imbalance, precipitated by renal failure, could be a possible causal factor.
Asunto(s)
Complicaciones de la Diabetes , Enfermedades Cutáneas Vesiculoampollosas/etiología , Adulto , Biopsia , Humanos , Masculino , Enfermedades Cutáneas Vesiculoampollosas/patología , Luz Solar , Rayos UltravioletaRESUMEN
A distinctive acral erythema developed in four patients with myelogenous leukemia, subsequent to blood transfusions and intensive chemotherapy with cytarabine. The clinical and histopathologic features of the eruption were suggestive of a drug-induced toxic eruption. To our knowledge, only one previous similar case has been reported in the literature. For patients in whom this self-limited condition develops, reassurance should serve as the mainstay of therapy.
Asunto(s)
Eritema/patología , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide/terapia , Piel/patología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Transfusión Sanguínea , Terapia Combinada , Eritema/etiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Skin necrosis is a rare complication of heparin administration that is usually localized to injection sites. A 32-year-old insulin-dependent diabetic patient, receiving intravenous (IV) and low-dose heparin sodium therapy, had cutaneous necrosis in areas distant to the sites of injection. Prior to the onset of cutaneous lesions, thrombocytopenia develop]ed in the patient that may have been heparin induced. Heparin may induce the production of platelet aggregating immunoglobulins that predispose persons who are sensitive to the drug to thrombocytopenia, skin necrosis, and thrombotic events. Obesity, diabetes, and treatment with broad-spectrum antibiotics seem to increase the risk of such complications. Cutaneous necrosis secondary to heparin administration may serve as a warning of the potentially lethal complications of IV use. In patients in whom skin necrosis or thrombocytopenia develops, heparin therapy should be discontinued and anticoagulation with an oral agent should be considered.
Asunto(s)
Heparina/efectos adversos , Enfermedades de la Piel/inducido químicamente , Adulto , Femenino , Humanos , Necrosis , Piel/patología , Enfermedades de la Piel/patologíaRESUMEN
Malignant melanoma derives from melanocytic cells that possess the special biochemical pathway for the conversion of levodopa to melanin. Levodopa is widely employed in the treatment of Parkinson's disease, and several patients receiving levodopa have been observed to have acquired melanomas, raising concern about a possible relationship between this drug and the tumor. We encountered a 74-year-old woman in whom three distinct primary melanomas developed after she had been receiving long-term therapy with levodopa and a decarboxylase inhibitor. These lesions could be distinguished histologically from epidermotropic metastatic melanoma. Although the association between levodopa and melanoma is tenuous, careful monitoring of pigmentary changes in patients receiving levodopa is advised.
Asunto(s)
Levodopa/efectos adversos , Melanoma/inducido químicamente , Neoplasias Primarias Múltiples/inducido químicamente , Neoplasias Cutáneas/inducido químicamente , Anciano , Femenino , Humanos , Levodopa/administración & dosificación , Melanoma/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Cutáneas/patología , Temblor/tratamiento farmacológicoRESUMEN
We report herein the concurrent appearance of childhood pemphigus foliaceus and Graves' disease in a 14-year-old girl who was initially seen with crusted and hyperpigmented plaques on her chest, back, abdomen, and legs. The diagnosis of pemphigus foliaceus was confirmed by biopsy and immunofluorescent microscopic studies while the diagnosis of Graves' disease was based on clinical and laboratory findings. The coexistence of these two immune-mediated diseases in a single patient suggest that some persons may bear a unique predisposition to the development of two or more autoimmune-type disorders that may affect diverse organ systems.
Asunto(s)
Enfermedad de Graves/complicaciones , Pénfigo/complicaciones , Adolescente , Enfermedades Autoinmunes/patología , Femenino , Enfermedad de Graves/inmunología , Enfermedad de Graves/patología , Humanos , Pénfigo/inmunología , Pénfigo/patologíaRESUMEN
For the determination of the optimal RP-HPLC chromatographic conditions for the separation of imatinib mesylate and its impurity STI 509-00 experimental design 2(4) was applied. All the factors that affect imatinib mesylate/STI 509-00 separation, as well as their mutual interactions were investigated. Methanol and triethylamine content in the mobile phase, pH of the mobile phase and column temperature were independent variables or factors to be investigated in two levels: "low" and "high". Capacity factor was chosen as a dependent variable. From the experimentally determined capacity factor values, it was defined the factors that affect to chromatographic system the most. Applying response surface methodology the appropriate graphs were constructed from experimental points and optimal chromatographic conditions for the separation were defined. Optimal conditions for the separation of imatinib mesylate and STI 509-00 were obtained using X Terra 150 mm x 4.6 mm, particle size 5 microm column at 25 degrees C. Mobile phase consisted of 250 ml of methanol, 740 ml of water and 10 ml of triehylamine. pH of water phase was adjusted to 2.4 with 85% orthophosphoric acid and then methanol was added.
Asunto(s)
Antineoplásicos/análisis , Piperazinas/análisis , Pirimidinas/análisis , Antineoplásicos/sangre , Benzamidas , Cromatografía Líquida de Alta Presión , Contaminación de Medicamentos , Humanos , Mesilato de Imatinib , Indicadores y Reactivos , Modelos Lineales , Piperazinas/sangre , Pirimidinas/sangre , Estándares de Referencia , Soluciones , Solventes , Espectrofotometría UltravioletaRESUMEN
The reversed-phase high-performance liquid chromatographic (RP-HPLC) method has been developed and validated for the simultaneous determination of imatinib mesylate and of the impurity product in Glivec capsules (Novartis, Switzerland). Separations were performed on a X Terra 150 mm x 4.6 mm, 5 microm particle size column at 25 degrees C. The mobile phase was a mixture of methanol-water-triethylamine (25:74:1, v/v/v) with flow rate of 1.0 ml min(-1). pH value of water-triethylamine (TEA) was adjusted to 2.4 with orthophosphoric acid before adding of methanol. UV detection was performed at 267 nm. Acetaminophen was used as an internal standard. The method was validated statistically for its selectivity, linearity, precision, accuracy and robustness. Due to its speed and accuracy, the method may be used for quality control analyses.
Asunto(s)
Antineoplásicos/análisis , Piperazinas/análisis , Pirimidinas/análisis , Benzamidas , Cápsulas , Cromatografía Líquida de Alta Presión , Contaminación de Medicamentos , Concentración de Iones de Hidrógeno , Mesilato de Imatinib , Indicadores y Reactivos , Estándares de Referencia , Reproducibilidad de los Resultados , Soluciones , Espectrofotometría Ultravioleta , Compuestos de Tetraetilamonio/químicaRESUMEN
A reversed-phase ion-pair high-performance liquid chromatografic method (RP-IPC) was developed to assay some water-soluble vitamins in solution dosage forms. Vitamins of the B-group B1, B2, B3, and B6, including vitamin C were determined in Oligovit coated tablets. In Beviplex coated tablets the vitamins B1, B2, B3, B6 and p-aminobenzoic acid were analysed. Hexanesulphonic acid sodium salt and triethanolamine in water methanol were used as mobile phase with adjusting pH to 2.8 with orthophosphoric acid. Phenol was used as an internal standard. For quantitative simultaneous analysis of vitamins in pharmaceutical formulations, the method of internal standard was used. All parameters for the validation of the method are given.
Asunto(s)
Vitaminas/análisis , Ácido Ascórbico/análisis , Cromatografía Líquida de Alta Presión , Excipientes , Concentración de Iones de Hidrógeno , Indicadores y Reactivos , Estándares de Referencia , Solubilidad , Comprimidos Recubiertos , Complejo Vitamínico B/análisisRESUMEN
In this paper the second-derivative spectrophotometric and ion-pair reversed-phase high performance liquid chromatographic methods for the simultaneous determination of some diuretic ingredients are described. Optimal conditions of both techniques for the quantitative analysis of the two-component diuretic mixture of the Lometazid tablets were settled. The second-derivative order of the spectra in sodium hydroxide with the wavelength modulation was used. For the determination of amiloride hydrochloride the 'zero-crossing' technique was applied, but for methyclothiazide the peak amplitude had to be corrected. In the ion-pair RP-HPLC technique tetrabutylammonium hydroxide was applied as an ion-pairing agent using acetonitrile-phosphate buffer (45:55 v/v) as a mobile phase. The validation was done of both proposed methods.