Currently, the pharmaceutical industry devotes great attention to drug degradation products because these compounds can offer risks to patients. A previous degradation study of betahistine (N-α-methyl-2-pyridylethylamine) conducted under different stress conditions detected three main impurities named A, B and C. Degradation products were analyzed by high-resolution mass spectrometry in electrospray source and time of flight analyzer (ESI-TOF) and nuclear magnetic resonance (NMR). Impurity mutagenicity was evaluated by Derek Nexus and Sarah Nexus softwares. Liquid chromatography hyphenate with tandem mass spectrometry (LC-MS/MS) analysis of the betahistine forced degradation sample indicated the presence of a new impurity, which was named impurity C1. 2D NMR experiments allowed the complete structural characterization of the new entity. The active pharmaceutical ingredient and degradation impurities were classified as inactive in the in silico mutagenic studies. Systematic investigation of a forced degradation sample led to the characterization of a new betahistine impurity. The in silico mutagenicity study of the betahistine degradation impurities may be useful in the risk assessment of the drug products.

OBJETIVO: Investigar a associação entre parâmetros histológicos do carcinoma papilífero da tireoide (CPT) e a presença de tireoidite de Hashimoto (TH). MATERIAIS E MÉTODOS: Amostra de tecidos de CPT foi revista por um médico patologista. Os seguintes parâmetros foram avaliados: presença de TH concomitante, multicentricidade, metástase linfonodal, tamanho tumoral, invasão vascular, infiltração perineural, variante histológica e estadiamento patológico. Os dados clínicos incluíam gênero e idade ao diagnóstico. RESULTADOS: Um total de 94 casos de CPT foi revisto. Houve predomínio do sexo feminino (85,1% vs. 14,9%) e a idade média de apresentação foi de 45,13 anos. A presença de TH foi associada a maior ocorrência de tumores multifocais (p = 0,004), estágios iniciais de estadiamento (p = 0,02) e tumores menores (p = 0,025). CONCLUSÃO: O CPT associado a TH apresentou-se com menor dimensão, maior ocorrência de multifocalidade e em estadiamentos mais iniciais do que os casos de CPT sem TH associada. Um melhor entendimento da resposta imune envolvida nesses tumores pode ser útil para estratégias futuras de prevenção e para o desenvolvimento de novas abordagens terapêuticas para esse tipo de neoplasia.

OBJECTIVE: To investigate the association between the histological parameters of papillary thyroid cancer (PTC) and the presence of Hashimoto's thyroiditis (HT). MATERIALS AND METHODS: Histological samples from patients with PTC were reviewed by an endocrine pathologist. The following parameters were analyzed: presence of concomitant HT, multifocality, presence of nodal metastasis, tumor size, vascular invasion, perineural infiltration, histological variant, and pathological staging. Clinical data included gender and age at the time of the diagnosis. RESULTS: A total of 94 cases of PTC were reviewed. There was a predominance of women (85.1% vs. 14.9%) and median age at presentation was 45.13 years. The presence of HT was significantly associated with greater occurrence of multifocal tumors (p = 0.004), early pathological stage (p = 0.02), and smaller tumor size (p = 0.025). CONCLUSIONS: Patients with PTC associated with HT had significantly smaller tumors, more often multifocal and in an earlier stage than their counterparts without HT. A better understanding of the immune response involved in these tumors may be useful for future strategies on the prevention and for the development of new therapeutic approaches for this group of neoplasms.

Foi desenvolvido um procedimento para tetrahidropiranilação de álcoois e tióis em ausência de solvente orgânico, baseado na simples mistura dos reagentes, na presença de sílica gel e quantidade catalítica de p-TSA.

A solvent-free procedure for tetrahydropyranylation of alcohols and thiols based on a simple grinding of the reagents in the presence of silica gel and catalytic amounts of p-TSA is described.