ABSTRACT
Omarigliptin (OMG) is an antidiabetic drug indicated for the treatment of type 2 diabetes mellitus. Forced degradation studies are practical experiments to evaluate the stability of drugs and to establish degradation profiles. Herein, we present the investigation of the degradation products (DPs) of OMG formed under various stress conditions. OMG was subjected to hydrolytic (alkaline and acidic), oxidative, thermal, and photolytic forced degradation. A stability-indicating ultra-fast liquid chromatography method was applied to separate and quantify OMG and its DPs. Five DPs were adequately separated and detected in less than 6 min, while other published methods detected four DPs. MS was applied to identify and obtain information on the structural elucidation of the DPs. Three m/z DPs confirmed previously published research, and two novel DPs were described in this paper. The toxicity of OMG and its DPs were investigated for the first time using in vitro cytotoxicity assays, and the sample under oxidative conditions presented significant cytotoxicity. Based on the results from forced degradation studies, OMG was found to be labile to hydrolysis, oxidation, photolytic, and thermal stress conditions. The results of this study contribute to the quality control and stability profile of OMG.
Subject(s)
Drug Stability , Heterocyclic Compounds, 2-Ring , Pyrans , Chromatography, High Pressure Liquid/methods , Pyrans/chemistry , Pyrans/analysis , Pyrans/toxicity , Heterocyclic Compounds, 2-Ring/chemistry , Heterocyclic Compounds, 2-Ring/analysis , Heterocyclic Compounds, 2-Ring/toxicity , Mass Spectrometry/methods , Humans , Cell Survival/drug effects , Reproducibility of Results , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/analysis , Oxidation-Reduction , Linear ModelsABSTRACT
Objetivo: Estimar perfil epidemiológico do consumo de álcool e tabaco durante a gravidez entre mulheres atendidas em maternidade de Santa Catarina. Métodos: Entrevistaram-se 157 mulheres, foram coletados dados sócio-demográficos e gestacionais, bem como informações sobre uso de álcool (incluindo questionário T-ACE) e tabaco (incluindo Questionário de Tolerância de Fagerström-QTF). Empregaram-se os testes qui-quadrado de Pearson ou Fisher (quando pertinente) e U de Mann-Whitney com nível de significância 95%, seguido de análise multivariada através de regressão logística. Resultados: O consumo alcoólico foi 36,9%. Na avaliação do T-ACE 22,9% foram positivas. A prática religiosa foi fator protetor para o álcool, as demais variáveis não. Não associaram-se fatores com resultado T-ACE. O hábito tabagístico foi de 14% e no QTF, 41,1% apresentaram dependência leve, 29,4% moderada ou grave. Menor escolaridade e ausência de prática religiosa associaram-se ao tabagismo. Houve consumo simultâneo das duas drogas. Conclusões: O consumo de álcool e tabaco no período gestacional não se caracterizou como evento incomum neste estudo. Praticar religião foi fator protetor para consumo de ambos, porém o tabagismo também esteve relacionado a menor escolaridade. Havendo, portanto indicativo de disseminação do álcool de forma mais homogênea e democrática nas diferentes classes sociais.
Objective: Estimate the epidemic profile of the consumption of alcohol and tobacco during the pregnancy period among women assisted at a maternity in Santa Catarina. Methods: Social-demographic and pregnancy data were collected from 157 women , as well as information on use of alcohol (including questionnaire T-ACE) and tobacco (including Questionary of Tolerance of Fagerström-QTF). The tests Qui-square of Pearson or Fisher were used (as pertinent) and U of Mann-Whitney with significance level of 95%, following by multi-sorted analysis through the regression logistics. Results: The alcoholic consumption was 36,9%. In T-ACE the evaluation of 22,9% was positive. The religious practice went protecting factor to alcohol, the other variables not. They didn't associate factors with resulted T-ACE. The habit of tabagism was of 14% and in QTF, 41,1% demonstrated light dependence, 29,4% moderate or serious. Low education level and absence of religious practicing were associated to the tabagism. There was simultaneous consumption of the two drugs. Conclusions: The consumption of the alcohol and the tobacco in the pregnancy period was not characterized as uncommon event in this study. To have a religion went protecting factor to consumption of both, however the tabagism was also related to the lowest education, therefore being an indicative of spread of the alcohol in a more homogeneous and democratic way in the different social classes.
