Ácidos graxos de cadeia muito longa em pacientes com diferentes formas clínicas de adrenoleucodistrofia ligada ao X : o efeito do Óleo de Lorenzo

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Estresse oxidativo em pacientes com diferentes formas clínicas de adrenoleucodistrofia ligada ao X

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Evaluation of pharmacokinetic of mazindol in plasma, urine And oral fluide and validation of analytics methods

Segundo a International Narcotics Control Board (INCB), o consumo medicamentos estimulantes anorexígenos nas Américas é o maior do mundo. Embora a quantidade de substâncias anorexígenas estimulantes consumida no Brasil tenha diminuído, altos níveis dessas substâncias ainda são consumidos nos Estados Unidos e na Argentina. Com o objetivo de manter o estado de alerta por longos períodos, motoristas profissionais utilizam essas substâncias, representando um grande risco da ocorrência de acidentes, tornando fundamental o monitoramento dessas substâncias para a prevenção de acidentes. O mazindol é um fármaco quimicamente não relacionado às anfetaminas, porém também possui característica anorexígena e estimulante do SNC e assim como a anfepramona e o femproporex foram recentemente retirados do mercado brasileiro com o argumento de não fornecer segurança quando utilizadas por longo período. Entretanto, mesmo com sua comercialização suspensa, pode ser obtido ilegalmente. Não há na literatura um método para a quantificação do fármaco em fluido oral, nem estudos de farmacocinética nesta matriz e também, não se sabe se sabe se há uma correlação entre os níveis do mazindol em plasma e em fluido oral. Face ao exposto, o presente estudo tem por objetivo geral desenvolver e validar técnicas cromatográficas sensíveis para a quantificação do mazindol em fluido oral, plasma e urina de voluntários, bem como avaliar sua farmacocinética e correlação entre os níveis plasmáticos e salivares do fármaco. Segundo as análises de caracterização da substância química de referência do mazindol (SQR) por espectroscopia nas regiões do infravermelho (IV) e do ultravioleta (UV), cromatografia líquida de alta eficiência (CLAE), e espectrometria de massas (EM), foi possível confirmar a identidade da amostra, permitindo o emprego da SQR para estudos posteriores. Metodologias para a determinação do mazindol em plasma, fluido oral e urina por cromatografia líquida acoplada à espectrometria de massas (CLAE/EM) foram desenvolvidas, validadas. Os métodos foram aplicados com sucesso na estimação do perfil farmacocinético do mazindol no fluido oral, plasma e urina de sete indivíduos do sexo masculino, após a administração de dose única de especialidade farmacêutica contendo 2 mg de mazindol.According to the International Narcotics Control Board (INCB), the consumption of anorectic stimulant in the Americas is the largest in the world. Although the amount of anorectic stimulants consumed in Brazil has decreased, high levels are still consumed of these substances in the United States and Argentina. Aiming to maintain alertness for long time, professional drivers use these substances, representing a high risk of accidents, and making it essential to monitor these substances to prevent accidents. Mazindol is a drug chemically not related to amphetamines, but has anorexigenic and CNS stimulant action. As amfepramone and femproporex, mazindol was recently withdrawn from the market motivated by dubious risk-benefit ratio when used for long periods. However, even with its commercialization suspended, like other illicit substances, it can be obtained illicitly. Moreover, no method was found reporting the quantification of the drug in oral fluid, neither pharmacokinetic studies in this matrix nor the correlation between plasma and oral fluid levels. Therefore, this study aims to develop and validate methods for the quantification of mazindol in plasma, urine and oral fluid of volunteers as well as evaluate its pharmacokinetics and correlation between salivary and plasma levels of mazindol. The characterization of the reference chemical substance was performe by: infrared (IR) and ultraviolet (UV) spectrophotoscopic methods, as well as mass spectrometry. Thus, methods for determination of mazindol in human oral fluid, plasma and urine by liquid chromatography-mass spectrometry (LC/MS) were developed and validated. The methods were successfully applied to estimate the pharmacokinetic profile of mazindol in oral fluid, plasma and urine of seven male subjects after administration of a single dose of 2 mg mazindol

Development, validation and comparison of two stability-indicating RP-LC methods using charged aerosol and UV detectors for analysis of lisdexamfetamine dimesylate in capsules

Two new stability-indicating liquid chromatographic methods using two detectors, an ultraviolet (UV) and a charged aerosol detector (CAD) simultaneously connected in series were validated for the assessment of lisdexamfetamine dimesylate (LDX) in capsule. The method was optimized and the influence of individual parameters on UV and CAD response and sensitivity was studied. Chromatography was performed on a Zorbax CN column (250 mm × 4.6 mm, 5 μm) in an isocratic elution mode, using acetonitrile and 20 mM ammonium formate at pH 4.0 (50:50, v/v) as mobile phase and UV detection at 207 nm. The developed method was validated according to ICH guidelines and the parameters’ specificity, limit of detection, limit of quantitation, linearity, accuracy, precision and robustness were evaluated. CAD is designated to be a non-linear detector in a wide dynamic range, however, the method was linear over the concentration range of 70–130 μg mL−1 in both detectors. The method was precise and accurate. Robustness study was performed by a Plackett–Burman design, delivering results within the acceptable range. Neither the excipients nor the degradation products showed interference in the method after studies of specificity as well as under stress conditions. The results of the LC-UV and LC-CAD methods were statistically compared through ANOVA and showed no significant difference (p > 0.05). Both proposed methods could be considered interchangeable and stability-indicating, and can be applied as an appropriate quality control tool for routine analysis of LDX in capsule

Avaliação de parâmetros de estresse oxidativo em pacientes portadores de fenilcetonúria

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