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1.
Drug Dev Ind Pharm ; 47(6): 867-877, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34224277

RESUMO

Flumethasone pivalate (FP) and clioquinol (CL) formulation was developed as a prodigious remedy to cure the external ear inflammatory disorders. So, the current research introduces five smart and novel UV-spectrophotometric platforms relying on minimal mathematical manipulation steps for simultaneous green analysis of FP and CL with no preliminary separation in their formulation that suffered from the high difference of their ratio and severe spectral overlapping. These platforms involved dual-wavelength, first derivative ratio, Fourier self-deconvolution, area under the curve, and bivariate methods. The suggested platform' linearity was observed over the concentration range of 3-42 µg/ml for FP and 1.5-8 µg/ml for CL. All suggested platforms were validated according to ICH recommendations regarding accuracy, precision, repeatability, and selectivity producing satisfactory results within the accepted limits. These platforms were represented as rapid, green, and cheap alternatives to the reported chromatographic method due to lower solvent consumption and waste generation. Furthermore, they improved the determination sensitivity of the studied drugs and enhanced the recorded data signals or its spectral resolution by the newly introduced Fourier self-deconvoluted method. The statistical comparison between the results of the suggested platforms with each other and with those of the reported method showed no significant differences between them.


Assuntos
Clioquinol , Flumetasona/análogos & derivados , Espectrofotometria
2.
Cancer Lett ; 474: 94-105, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31954771

RESUMO

Nuclear factor erythroid-2-related factor 2 (Nrf2), a transcription factor, participates in protecting cells from electrophilic or oxidative stresses through regulating expression of cytoprotective and antioxidant genes. It has become one of the emerging targets for cancer chemosensitization, and small molecule inhibitors of Nrf2 can enhance the efficacy of chemotherapeutic drugs. Here, we found that flumethasone, a glucocorticoid, inhibited Nrf2 signaling in A549 and H460 cells by promoting Nrf2 protein degradation. Moreover, flumethasone significantly increased the sensitivity of A549 and H460 cells to chemotherapeutic drugs including cisplatin, doxorubicin and 5-FU. In mice bearing A549-shControl cells-derived xenografts, the size and weight of xenografts in the flumethasone and cisplatin combination group had a significant reduction compared with those in the cisplatin group, while in mice bearing A549-shNrf2 cells-derived xenografts, the size and weight of the xenografts in the combination group had no significant difference compared with those in the cisplatin group, demonstrating that chemosensitization effect of flumethasone is Nrf2-dependent. This work suggests that flumethasone can potentially be used as an adjuvant sensitizer to enhance the efficacy of chemotherapeutic drugs in lung cancer.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Sinergismo Farmacológico , Flumetasona/farmacologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/tratamento farmacológico , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Animais , Anti-Inflamatórios/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Quimioterapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Sci Total Environ ; 672: 183-191, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30954817

RESUMO

Many glucocorticoids occur in the aquatic environments but their adverse effects to fish are poorly known. Here we investigate effects of the natural glucocorticoid corticosterone and the synthetic glucocorticoids betamethasone and flumethasone in zebrafish embryos. Besides studying the effects of each steroid, we compared effects of natural with synthetic glucocorticoids, used as drugs. Exposure at concentrations of 1 µg/L and higher led to concentration-related decrease in spontaneous muscle contractions at 24 h post fertilization (hpf) and increase in heart rate at 48 hpf. Betamethasone showed a significant increase at 0.11 µg/L in heart rate. Corticosterone also accelerated hatching at 60 hpf at 0.085 µg/L. Transcription of up to 24 genes associated with different pathways showed alterations at 96 and 120 hpf for all glucocorticoids, although with low potency. Corticosterone caused transcriptional induction of interleukin-17, while betamethasone caused transcriptional down-regulation of the androgen receptor, aromatase and hsd11b2, indicating an effect on the sex hormone system. Furthermore, transcripts encoding proteins related to immune system regulation (irg1l, gilz) and fkbp5 were differentially expressed by corticosterone and betamethasone, while flumethasone caused only little effects, mainly alteration of the irg1l transcript. Our study shows that these glucocorticoids caused more potent physiological effects in early embryos than transcriptional alterations in hatched embryos, likely due to increased metabolism in later developmental stages. Thus, these glucocorticoids may be of concern for early stages of fish embryos in contaminated aquatic environments.


Assuntos
Betametasona/toxicidade , Corticosterona/toxicidade , Embrião não Mamífero/fisiologia , Flumetasona/toxicidade , Glucocorticoides/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia , Animais , Peixe-Zebra/fisiologia
4.
Equine Vet J ; 51(2): 238-245, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30080272

RESUMO

BACKGROUND: Flumetasone is a potent corticosteroid reportedly used in horses to decrease inflammation associated with strenuous exercise. There are currently no reports describing the use of this drug in horses. OBJECTIVES: To describe the pharmacokinetics and effects on cortisol and eicosanoid concentrations, following administration of flumetasone to exercised horses. STUDY DESIGN: Parallel design. METHODS: Twelve exercised horses received a single i.v. administration of 5 mg of flumetasone. Blood and urine samples were collected before and for 72 h post-drug administration for determination of flumetasone and cortisol concentrations. Whole blood samples were collected at various time and challenged with lipopolysaccharide, calcium ionophore or methanol to induce ex vivo synthesis of eicosanoids. Concentrations of flumetasone, cortisol and eicosanoids were measured using LC-MS/MS and pharmacokinetic/pharmacodynamic analysis performed. RESULTS: Flumetasone was detected for 23.5 ± 1.73 h in blood. The volume of distribution at steady state, systemic clearance and elimination half-life was 5.90 ± 0.200 L/kg, 30.7 ± 0.166 mL/min/kg and 4.84 ± 0.83 h respectively. Cortisol concentrations were still suppressed at last time point collected (72 h). For cortisol, Kin , Kout and the t1/2out were 30.3 ± 1.56 ng/mL × h, 0.331 ± 0.02 1/h and 2.1 h respectively. Stimulation with lipopolysaccharide resulted in a decrease in TXB2 , PGF2 , LTB4 , 15-HETE and 5-HETE for up to 72 h and PGE2 for 24 h post-flumetasone administration. Stimulation of whole blood with calcium ionophore resulted in a decrease in LTB4 for up to 6 h and 15-HETE at 8 h. MAIN LIMITATIONS: Lack of sample collection for determination of biomarker concentrations beyond 72 h and the use of a single sample for determination of baseline cortisol concentrations. CONCLUSIONS: Flumetasone is rapidly cleared from blood following administration to horses. It is a potent anti-inflammatory with prolonged effects on production of cortisol and other inflammatory mediators.


Assuntos
Flumetasona/farmacocinética , Cavalos/fisiologia , Hidrocortisona/sangue , Inflamação/veterinária , Animais , Área Sob a Curva , Biomarcadores , Citocinas/genética , Citocinas/metabolismo , Flumetasona/sangue , Flumetasona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/sangue , Glucocorticoides/farmacocinética , Meia-Vida , Cavalos/sangue , Inflamação/metabolismo
5.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 43(2): 173-178, 2018 Feb 28.
Artigo em Chinês | MEDLINE | ID: mdl-29559602

RESUMO

OBJECTIVE: To compare the efficacy and safety between ozonated oil and compound flumethasone ointment in the treatment of psoriasis vulgaris.
 Methods: A left/right self-controlled, parallel group study was conducted. Forty patients with stable psoriasis vulgaris were enrolled in the study, whose lesions were symmetrical and involvement areas were <30% body surface. The patients were divided into 2 groups. Patients with left lesions served as a test group were treated daily for ozonated oil twice, and patients with right lesions served as a control group were treated daily for compound flumetasone ointment twice. The patients in the 2 groups were treated for 4 weeks. The clinical efficacy and safety were observed at 1, 2 and 4 weeks after the treatment.
 Results: After 1 week treatment, the effective rates of the test group and the control group were 60.58% and 72.28%, respectively, with significant difference between them (P<0.05). At 2 weeks and 4 weeks after the treatment, the efficacy in the test group was similar to that in the control group. The effective rates in the test group and the control group were 69.84% and 70.25% after 2 weeks, respectively, 70.88% and 71.23% after 4 weeks, respectively. There was no significant difference between the 2 groups (P<0.05). In addition, the reflectance confocal microscope results in both the test group and the control group after 4 weeks showed that the epidermis was approximately normal. There were few inflammatory cells infiltration in the dermal papilla, and the inflammatory cells infiltration was significantly reduced after treatment.
 Conclusion: Ozonated oil treatment for stable psoriasis is safe and effective, and its efficacy is equivalent to the effect of glucocorticoid topical preparations.


Assuntos
Óleos/uso terapêutico , Ozônio/uso terapêutico , Psoríase/terapia , Anti-Inflamatórios/administração & dosagem , Calcitriol , Estudos de Casos e Controles , Esquema de Medicação , Flumetasona/administração & dosagem , Glucocorticoides , Humanos , Pomadas , Psoríase/patologia , Resultado do Tratamento
6.
Drug Test Anal ; 10(4): 742-749, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28994213

RESUMO

The aim of this project was to develop and validate a new test for the analysis of glucocorticoids in camel hair and to use the new test to analyse hair samples from a variety of camel breeds in sports and racing applications. These findings could be of importance when evaluating racing camels for suspected doping offenses or for injury and disease control. Camel hair samples were collected from 30 non-racing dromedary camels along with 3 racing camels in Al Ain, UAE and were decontaminated, pulverised, sonicated, and extracted prior to analysis. A liquid chromatographic-mass spectrometric method was employed to determine the levels of glucocorticoids in the hair samples. The 4 drugs of interest, namely hydrocortisone, dexamethasone, flumethasone and methylprednisolone, and an internal standard were quantified in camel hair samples. All 4 of the glucocorticoids were detected in camel hair samples with concentrations ranging between 31 and 935 pg/mg for hydrocortisone, 8-59 pg/mg for dexamethasone, 0.7-1034 pg/mg for flumethasone and 5-66 pg/mg for methylprednisolone in non-racing camels. One of the racing camels displayed high concentrations of hydrocortisone (1130 pg/mg), flumethasone (2576 pg/mg), methylprednisone (1156 pg/mg) and dexamethasone (29 pg/mg). The authors believe this is the first report of a test for corticosteroids in camel hair. The new test has been validated according to Food and Drug Administration (FDA) guidelines. This new hair test could be useful for further studies in doping control, toxicological studies, pharmacological studies and other clinical applications in camel health, injury, and disease.


Assuntos
Pelo Animal/química , Camelus , Glucocorticoides/análise , Espectrometria de Massas em Tandem/métodos , Animais , Camelus/metabolismo , Cromatografia Líquida/métodos , Dexametasona/análise , Doping nos Esportes , Flumetasona/análise , Hidrocortisona/análise , Limite de Detecção , Metilprednisolona/análise , Detecção do Abuso de Substâncias/métodos
7.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1012-1013: 8-16, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26797492

RESUMO

A simple analytical method based on liquid chromatography coupled with triple-quadrupole mass spectrometry was developed for detection of the veterinary drugs flumethasone, dl-methylephedrine, and 2-hydroxy-4,6-dimethylpyrimidine in porcine muscle and pasteurized cow milk. The target drugs were extracted from samples using 10mM ammonium formate in acetonitrile followed by clean-up with n-hexane and primary secondary amine sorbent (PSA). The analytes were separated on an XBridge™ hydrophilic interaction liquid chromatography (HILIC) column using 10mM ammonium formate in ultrapure water and acetonitrile. Good linearity was achieved over the tested concentrations in matrix-fortified calibrations with correlation coefficients (R(2))≥0.9686. Recovery at two spiking levels ranged between 73.62-112.70% with intra- and inter-day precisions of ≤20.33%. The limits of quantification ranged from 2-10ng/g in porcine muscle and pasteurized cow milk. A survey of market samples showed that none of them contained any of the target analytes. Liquid-liquid purification using n-hexane in combination with PSA efficiently removed the interferences during porcine and milk sample extraction. The developed method is sensitive and reliable for detection of the three target drugs in a single chromatographic run. Furthermore, it exhibits high selectivity and low quantification limits for animal-derived food products destined for human consumption.


Assuntos
Cromatografia Líquida/métodos , Efedrina/análogos & derivados , Flumetasona/análise , Leite/química , Músculo Esquelético/química , Pirimidinonas/análise , Espectrometria de Massas em Tandem/métodos , Animais , Bovinos , Efedrina/análise , Carne/análise , Suínos
8.
Laryngoscope ; 126(6): 1411-9, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26600419

RESUMO

OBJECTIVES/HYPOTHESIS: The goal of this systematic review was to compare the efficacy and ototoxicity of Locacorten-Vioform (Paladin Labs Inc., Montreal, Quebec, Canada) and clotrimazole in the treatment of patients with otomycosis. DATA SOURCES: Embase, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, World Health Organization International Clinical Trials Registry Platform, European Union Clinical Trials Register, Cochrane Library databases of clinical trials, and ClinicalTrials.gov. METHODS: We included any randomized controlled trials or nonrandomized studies (case-control, cohort, and case series) assessing the topical use of Locacorten-Vioform (Paladin Labs Inc.) and/or clotrimazole in adult and/or pediatric immunocompetent patient population with otomycosis. DerSimonian and Laird's random effects approach was used for meta-analysis, followed by an assessment of heterogeneity and subgroup analysis. RESULTS: Of 226 reviewed articles, 14 were retained. Clotrimazole efficacy rate was 85% (95% confidence interval [CI]: 79.7-89.0%), whereas Locacorten-Vioform (Paladin Labs Inc.) was 73% (95% CI: 56.0-84.5%). Overall, study quality was low. There was high heterogeneity in both groups (I(2) of 47 and 49). There were only three studies assessing Locacorten-Vioform (Paladin Labs Inc.); therefore, comparative assessment was not possible. A one-way meta-analysis involving 13 clotrimazole studies was performed. Heterogeneity across studies was high; however, studies using objective analysis assessing treatment efficacy, randomized controlled trials, studies using drops, studies performed in Asia, and studies where Candida was the major fungus at diagnosis demonstrated low heterogeneity. CONCLUSION: Although both are safe and effective, there is insufficient evidence supporting increased efficacy of either clotrimazole or Locacorten-Vioform (Paladin Labs Inc.) for the treatment of otomycosis. High-quality comparative studies are required. LEVEL OF EVIDENCE: N/A. Laryngoscope, 126:1411-1419, 2016.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Candidíase/tratamento farmacológico , Clioquinol/administração & dosagem , Clotrimazol/administração & dosagem , Flumetasona/análogos & derivados , Otomicose/tratamento farmacológico , Administração Tópica , Adolescente , Adulto , Criança , Combinação de Medicamentos , Feminino , Flumetasona/administração & dosagem , Humanos , Masculino , Resultado do Tratamento , Adulto Jovem
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 136 Pt B: 707-13, 2015 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-25448970

RESUMO

This work is concerned with development and validation of three simple, specific, accurate and precise spectrophotometric methods for determination of flumethasone pivalate (FP) and clioquinol (CL) in their binary mixture and ear drops. Method A is a ratio subtraction spectrophotometric one (RSM). Method B is a ratio difference spectrophotometric one (RDSM), while method C is a mean center spectrophotometric one (MCR). The calibration curves are linear over the concentration range of 3-45 µg/mL for FP, and 2-25 µg/mL for CL. The specificity of the developed methods was assessed by analyzing different laboratory prepared mixtures of the FP and CL. The three methods were validated as per ICH guidelines; accuracy, precision and repeatability are found to be within the acceptable limits.


Assuntos
Anti-Infecciosos/análise , Clioquinol/análise , Flumetasona/análogos & derivados , Glucocorticoides/análise , Soluções Farmacêuticas/química , Espectrofotometria/métodos , Combinação de Medicamentos , Flumetasona/análise , Reprodutibilidade dos Testes
10.
Meat Sci ; 92(4): 749-53, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22819726

RESUMO

A rapid, specific, and sensitive method based on liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) in the positive ion mode using multiple reaction monitoring (MRM) was developed and validated to quantify flumethasone residues in beef muscle. Methods were compared between the original as well as the EN quick, easy, cheap, effective, rugged, and safe (QuEChERS)-based extraction. Good linearity was achieved at concentration levels of 5-30 µg/kg. Estimated recovery rates at spiking levels of 5 and 10 µg/kg ranged from 72.1 to 84.6%, with relative standard deviations (RSDs)<7%. The results of the inter-day study, which was performed by fortifying beef muscle samples (n=18) on 3 separate days, showed an accuracy of 93.4-94.4%. The precision (expressed as relative standard deviation values) for the inter-day variation at two levels of fortification (10 and 20 µg/kg) was 1.9-5.2%. The limit of detection (LOD) and limit of quantitation (LOQ) were 1.7 and 5 µg/kg, at signal-to-noise ratios (S/Ns) of 3 and 10, respectively. The method was successfully applied to analyze real samples obtained from large markets throughout the Korean Peninsula. The method proved to be sensitive and reliable and, thus, rendered an appropriate means for residue analysis studies.


Assuntos
Resíduos de Drogas/análise , Flumetasona/análise , Contaminação de Alimentos , Inspeção de Alimentos/métodos , Glucocorticoides/análise , Carne/análise , Músculo Esquelético/química , Animais , Calibragem , Bovinos , Cromatografia Líquida de Alta Pressão , Redução de Custos , Resíduos de Drogas/isolamento & purificação , Flumetasona/isolamento & purificação , Inspeção de Alimentos/economia , Glucocorticoides/isolamento & purificação , Limite de Detecção , Carne/economia , Reprodutibilidade dos Testes , República da Coreia , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Fatores de Tempo , Extratos de Tecidos/química , Extratos de Tecidos/isolamento & purificação
11.
Photodermatol Photoimmunol Photomed ; 28(3): 133-6, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22548394

RESUMO

OBJECTIVE: To compare the clinical efficacy and safety of combining flumetasone ointment with 308-nm excimer laser therapy vs. 308-nm excimer laser monotherapy for the treatment of psoriasis vulgaris. METHOD: Forty patients with psoriasis vulgaris were recruited; 20 were treated with flumetasone ointment plus 308-nm excimer laser therapy, and the other 20 received only excimer laser monotherapy. The flumetasone ointment was applied topically twice a day, and laser treatments were scheduled twice weekly for a total of 10 treatments. Clinical efficacy was evaluated in a blinded manner by two independent physicians using photographs taken before and after treatment. RESULTS: Of the 40 patients who received and completed the entire course of therapy, the psoriasis area and severity index score was improved by 82.51 ± 11.24% and 72.01 ± 20.94% in the combination group and laser group, respectively (P > 0.05), and the average cumulative dose was 5.06 ± 2.20 j/cm(2) in the combination group and 7.75 ± 2.25 j/cm(2) in the laser-only group, respectively (P < 0.05). CONCLUSION: The clinical data suggest that combination treatment using flumetasone ointment and a 308-nm excimer laser is superior to laser monotherapy for treatment of psoriasis vulgaris. The combination therapy can increase effectiveness and decrease the total laser dose, thus potentially reducing side effects.


Assuntos
Anti-Inflamatórios/administração & dosagem , Flumetasona/administração & dosagem , Ceratolíticos/administração & dosagem , Terapia a Laser/métodos , Psoríase/terapia , Ácido Salicílico/administração & dosagem , Administração Tópica , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pomadas , Fatores de Tempo
12.
J Laryngol Otol ; 125(8): 853-5, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21729449

RESUMO

The aim of tympanoplasty graft preparation is to stiffen the fascia or perichondrium and thereby to optimise ease of manipulation. We report 39 cases utilising a novel technique in which the graft is prepared in ear drops containing polyethylene glycol, flumetasone pivalate (0.02 per cent) and clioquinol (1 per cent). This technique is useful in reducing the risk of desiccation if placement is delayed, and may pose less risk of infection and mechanical damage than alternative methods.


Assuntos
Clioquinol/uso terapêutico , Flumetasona/análogos & derivados , Polietilenoglicóis/farmacologia , Perfuração da Membrana Timpânica/cirurgia , Timpanoplastia/métodos , Condução Óssea , Cartilagem/transplante , Clioquinol/química , Clioquinol/farmacologia , Combinação de Medicamentos , Flumetasona/química , Flumetasona/farmacologia , Flumetasona/uso terapêutico , Sobrevivência de Enxerto , Humanos , Polietilenoglicóis/química , Estudos Prospectivos
13.
J Photochem Photobiol B ; 103(1): 35-41, 2011 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-21324709

RESUMO

The photodegradation of flumethasone (FM) and fluocinolone acetonide (FC) was studied in solution and in the pig skin. Both glucocorticosteroids applied to the pig skin were unstable under UVB light. The photoproducts formed in the skin were the lumi-, photolumi- and andro-derivatives for FM, the same found in vitro. Instead, FC hydroperoxide formed in solution was not found in the skin: the reactivity and oxidative ability of this photoproduct towards biological substrates (lipids, proteins) seems the reason of the lack of its detection in the ex vivo model. In fact, it demonstrated to quickly oxidize amino acids and peptides, and to react with BSA both in the dark and under irradiation. Moreover, the presence in the irradiated pig skin of the FC andro-derivative, which usually forms in H-donating environment, seems consistent with the mechanism of Norrish I fragmentation followed by H-abstraction, likely from the surrounding biological substrates. These findings indicate that photoreactivity of these compounds may take place in the skin of patients exposing themselves to sunlight and is a warning about possible skin damage as a result of that. Furthermore, photolability of these drugs in the skin might cause loss of their therapeutic activity.


Assuntos
Flumetasona/química , Fluocinolona Acetonida/química , Fotólise/efeitos da radiação , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta , Aminoácidos/metabolismo , Animais , Bovinos , Flumetasona/metabolismo , Fluocinolona Acetonida/metabolismo , Oxirredução , Peptídeos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Soroalbumina Bovina/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-21112257

RESUMO

A rapid, simple and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay was developed for the determination of dexamethasone (Dex) and dexamethasone sodium phosphate (Dex SP) in plasma and human cochlear perilymph. After proteins were precipitated with a mixture of acetonitrile and methanol, Dex, Dex SP and flumethasone, the internal standard, were resolved on a C18 column using gradient elution of 5 mM ammonium acetate and methanol. The three compounds were detected using electrospray ionisation in the positive mode. Standard curves were linear over the concentration range 0.5-500 µg/L (r>0.99), bias was <±10%, intra- and inter-day coefficients of variation (imprecision) were <10%, and the limit of quantification was 0.5 µg/L for both Dex and Dex SP. The assay has been used successfully in a clinical pharmacokinetics study of Dex and Dex SP in cochlear perilymph and plasma.


Assuntos
Cromatografia Líquida/métodos , Cóclea/química , Dexametasona/análogos & derivados , Dexametasona/análise , Perilinfa/química , Espectrometria de Massas em Tandem/métodos , Dexametasona/sangue , Dexametasona/química , Estabilidade de Medicamentos , Flumetasona/análise , Humanos , Modelos Lineares , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray
15.
Int J Pharm ; 370(1-2): 181-6, 2009 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-19073240

RESUMO

Charged drug delivery systems are interesting candidates for the delivery of drugs through skin. In the present study, it was possible to create negatively and positively charged oil/water nanoemulsions by using sucrose laureate and polysorbate 80 as non-ionic surfactants. The positively charged nanoemulsions were generated by adding cationic phytosphingosine (PS). The relationship between the physicochemical properties of the nanoemulsions was shown by particle size and zeta potential measurements. These properties were dependent on the type of non-ionic surfactant and the concentration of PS. Furthermore the cationic PS had a positive impact on the skin permeation rates (flux) of the incorporated model drugs fludrocortisone acetate and flumethasone pivalate. An enhancement factor between 1.1 and 1.5 was obtained in relation to the control. The interaction of pre-impregnated porcine skin with positively and negatively charged nanoemulsions was confirmed by DSC analysis. The generated DSC-curves showed a slight difference in the phase transition temperature assigned to the characteristic lipid transition. However, it was not possible to assign the effect to one of the ingredients in the multicomponent system.


Assuntos
Anti-Inflamatórios/administração & dosagem , Sistemas de Liberação de Medicamentos , Fludrocortisona/administração & dosagem , Flumetasona/análogos & derivados , Nanopartículas , Esfingosina/análogos & derivados , Administração Tópica , Animais , Anti-Inflamatórios/química , Varredura Diferencial de Calorimetria , Química Farmacêutica , Composição de Medicamentos , Estabilidade de Medicamentos , Eletroquímica , Fludrocortisona/química , Flumetasona/administração & dosagem , Flumetasona/química , Técnicas In Vitro , Tamanho da Partícula , Polissorbatos/química , Pele/metabolismo , Absorção Cutânea , Solubilidade , Esfingosina/química , Sacarose/análogos & derivados , Sacarose/química , Tensoativos/química , Suínos
16.
Anal Bioanal Chem ; 391(7): 2683-91, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18506427

RESUMO

An HPLC-DAD method for determining corticoids in calf feed and in animal feeding water samples using a monolithic column has been developed and validated. The method optimization included the study of binary mobile phases of water and acetonitrile. The optimum separation was achieved at 40 degrees C, with acetonitrile:H(2)O 29:71 v/v used as mobile phase and a 3 ml/min flow-rate, which resulted in their separation in about 5 min. Two reported sample procedures were applied to feed and for animal feeding water samples prior to HPLC. Method validation was carried out according to the EU criteria established for quantitative screening methods. The results indicate that this method is highly specific, reproducible and accurate. The proposed method was found to be robust and unaffected by small variations in the extraction procedure and in HPLC conditions. The developed method for the determination of corticoids in feed and water samples was also found to be suitable for different kinds of feeds and waters.


Assuntos
Corticosteroides/análise , Ração Animal/análise , Cromatografia Líquida de Alta Pressão/métodos , Animais , Betametasona/análise , Calibragem , Bovinos , Cortisona/análogos & derivados , Cortisona/análise , Flumetasona/análise , Água Doce/análise , Prednisona , Reprodutibilidade dos Testes , Triancinolona Acetonida/análise
18.
Anal Chim Acta ; 588(1): 20-5, 2007 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-17386789

RESUMO

Dexamethasone, betamethasone and prednisolone are synthetic glucocorticosteroids authorized for therapeutic use in bovine animals within the European Union. Dexamethasone and betamethasone are used mainly for the treatment of metabolic and inflammatory diseases. Prednisolone is used to treat bovine mastitis. Maximum residue limits (MRLs) of 0.3 microg kg(-1) for both dexamethasone and betamethasone and 6.0 microg kg(-1) for prednisolone in bovine milk have been established. 6alpha-Methylprednisolone and flumethasone are not authorized for use in bovine animals and are completely banned in bovine milk. The proposed method is based on deprotenisation of milk using 20% (w/v) trichloroacetic acid. Samples are filtered using glass microfiber filters and subject to clean-up using OASIS HLB solid phase extraction. Separation was achieved on a Hypercarb 100 mm x 2.1 mm x 5 microm column. Mobile phase was: 90/10 acetonitrile/0.1% formic acid in water; flow rate was 600 microL min(-1). The method allowed the rapid identification and confirmation of the five glucocorticosteroids according to the criteria laid down in Commission Decision 2002/657/EC. Matrix calibration curves for all compounds were linear in the interval 0.0 MRL to 2.0 MRL with a correlation coefficient (r(2)) higher than 0.96. Relative recoveries ranged from 97% for betamethasone to 111% for prednisolone. Precision at the MRL ranged from 3.8% for prednisolone to 13.8% for betamethasone. Decision limits, CCalpha, and detection capability, CCbeta have been calculated for all compounds.


Assuntos
Corticosteroides/análise , Técnicas de Química Analítica/métodos , Cromatografia Líquida/métodos , Contaminação de Alimentos/análise , Leite/metabolismo , Espectrometria de Massas por Ionização por Electrospray/métodos , Animais , Betametasona/análise , Bovinos , Flumetasona/análise , Análise de Alimentos/métodos , Metilprednisolona/análise , Prednisolona/análise , Reprodutibilidade dos Testes
19.
J Pharm Biomed Anal ; 43(1): 376-80, 2007 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-16887316

RESUMO

Dexamethasone is a synthetic glucocorticoid with potent anti-inflammatory properties. However, its administration causes significant side effects, specially in long-term therapy. A new approach for limiting adverse effects consists in the slow and constant deliver of this drug, using dexamethasone-21-phosphate-loaded erythrocytes (RBC) as circulating bioreactors converting the non-diffusible dexamethasone-21-phosphate into the diffusible dexamethasone. In order to evaluate the real possibility to use this new method of administration, a simple, cheap and rapid assay was set to manage a large number of samples originating from clinical studies. Due to the sample complexity and analite polarity, electrospray mass spectrometry (MS) is the most powerful technique to achieve qualitative and quantitative data. In order to overcome the complex, time-consuming and expensive LC-MS/MS methods reported in the literature in the present work a standard fluxes HPLC-ESI-MS method was set up for quantitative evaluation of dexamethasone. Thanks to the extraction ion chromatogram (XIC) feature of the software, it was possible to obtain sharp profiles for dexamethasone (DXM) and for the employed internal standard (IS) flumethasone (FM), in spite of the extremely complicated chromatogram obtained after HPLC separation of acetonitrile extracted plasma sample, thus avoiding the use of the expensive deuterated internal standard. This enabled us to obtain a linear response curve, allowing the quantification of DXM from blood samples at the picomoles level.


Assuntos
Anti-Inflamatórios/sangue , Dexametasona/sangue , Cromatografia Líquida de Alta Pressão , Eritrócitos/química , Flumetasona/sangue , Hidrogênio/química , Indicadores e Reagentes , Padrões de Referência , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray
20.
Eur J Pharm Biopharm ; 66(1): 120-6, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17055710

RESUMO

The purpose of the present study was to investigate the influence of different drugs exhibiting different solubility on the viscoelastic properties and on the skin diffusion profile of a ringing gel. In a preliminary rheology study with the placebo gel predominating elastic properties were confirmed and a temperature influence was indicated. Fluconazole, fludrocortisone-acetate, flumethasone-pivalate, flutamide and flufenamic-acid each 1% (w/w) were incorporated into the preparation and oscillatory measurements were performed at temperatures of 25, 28, 32 and 37 degrees C. In all drug containing formulations a high elastic G' value predominated the viscous G'' value. The highest G' value could be obtained with the incorporated flumethasone-pivalate. Additionally in almost all cases the G' values decreased with increasing temperature compared to the placebo gel. Additionally in vitro standard diffusion experiments using Franz-type cells and porcine skin were performed. Following rank order of the cumulative drug release after 48 h was obtained: fluconazole>flufenamic-acid>flumethasone-pivalate>flutamide>fludrocortisone-acetate. Furthermore an excellent chemical stability of all incorporated drugs was confirmed over 10 weeks.


Assuntos
Compostos de Flúor/química , Preparações Farmacêuticas/química , Absorção Cutânea , Pele/metabolismo , Animais , Difusão , Estabilidade de Medicamentos , Fluconazol/química , Fluconazol/farmacocinética , Fludrocortisona/química , Fludrocortisona/farmacocinética , Ácido Flufenâmico/química , Ácido Flufenâmico/farmacocinética , Flumetasona/análogos & derivados , Flumetasona/química , Flumetasona/farmacocinética , Flutamida/química , Flutamida/farmacocinética , Géis , Interações Hidrofóbicas e Hidrofílicas , Técnicas In Vitro , Óleos/química , Parafina/química , Permeabilidade , Preparações Farmacêuticas/metabolismo , Temperatura Cutânea , Solubilidade , Tensoativos/química , Suínos , Viscosidade , Água/química
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