Abstract The illicit market of counterfeit medicines containing sildenafil and tadalafil has been causing serious public health problems. Thus, further studies on this illicit association are needed. A stability-indicating HPLC method was developed for simultaneous determination of tadalafil (TAD) and sildenafil (SIL) using a C18 column (250 x 4.6 mm, 5 µm). Detection was achieved at 284 nm, for TAD, and 292 nm, for SIL. The method was considered to be specific, linear, precise, accurate, robust, and sensitive. In the photodegradation kinetic studies, the drugs showed a first-order reaction rate when isolated, and zero-order when associated. Toxicological assays demonstrated that the photodegraded drugs decreased cell viability in compared to non- degraded drugs, suggesting cytotoxic activity. Additional, mutagenic activity was not observed under the tested conditions. Photodegraded drugs, in association, depicted DNA damage index, suggesting genotoxic effects. The obtained results will be able to support the forensic intelligence laboratories, as well as to alert the population about the risk inherent to consuming counterfeit products.

ABSTRACT Fluoroquinolones are a known antibacterial class commonly used around the world. These compounds present relative stability and they may show some adverse effects according their distinct chemical structures. The chemical hydrolysis of five fluoroquinolones was studied using alkaline and photolytic degradation aiming to observe the differences in molecular reactivity. DFT/B3LYP-6.31G* was used to assist with understanding the chemical structure degradation. Gemifloxacin underwent degradation in alkaline medium. Gemifloxacin and danofloxacin showed more degradation perceptual indices in comparison with ciprofloxacin, enrofloxacin and norfloxacin in photolytic conditions. Some structural features were observed which may influence degradation, such as the presence of five member rings attached to the quinolone ring and the electrostatic positive charges, showed in maps of potential electrostatic charges. These measurements may be used in the design of effective and more stable fluoroquinolones as well as the investigation of degradation products from stress stability assays.

OBJETIVOS: Avaliar o efeito do antimoniato de meglumina na transferência materno-fetal na geração F1 (prole de matrizes expostas ao composto), e conseqüências em progênies F2. MÉTODOS: Camundongos fêmeas Swiss foram tratados com antimoniato de meglumina, via subcutânea, com administração diária, do sétimo ao 12º dia de gestação (ddg), na dose equivalente a 100mgSb v/kg peso/dia. O grupo controle recebeu apenas o veículo (água destilada). Após o nascimento da prole (geração F1), 59 fêmeas foram examinadas diariamente para determinação do ciclo estral. Quando determinado o ciclo estro, acasalou-se 18 fêmeas com machos da mesma linhagem. No 18º ddg, as fêmeas foram eutanasiadas por câmara de CO2, o abdômen incisado e o útero exposto, quando avaliou-se os sítios de desenvolvimento embrionário e fetal quanto ao número de reabsorções, fetos vivos e mortos. Todos os fetos e placentas foram pesados para calcular o índice placentário. Três placentas de cada ninhada foram separadas para análise microscópica. RESULTADOS: A exposição ao antimoniato de meglumina não interferiu no ciclo estral dos animais tratados, pelo fato de não alterar o intervalo precoital e o índice de fertilidade. Não foram observadas alterações placentárias em progênies F2. CONCLUSÃO: O antimoniato de meglumina não altera a performance reprodutiva das mães expostas cronicamente. Estes dados sugerem que ocorre uma gradual eliminação do antimoniato de meglumina no organismo materno, sem acarretar danos a proles futuras.

OBJECTIVES: Evaluate the effect of Meglumine Antimoniate on maternal-fetal transference in F1 generations (offspring of dams exposed to the drug), and embryotoxicity in F2 generations. METHODS: Female Swiss mice were treated with daily s.c. injection of Meglumine Antimoniate (100mgSb v/kg bw/day) from day 7 until day 12 of pregnancy. The control group received only the vehicle (distilled water). After birth of offspring (F1 generation), 59 females were examined daily for determination of the estral cycle. When the cycle estrus was determined, males were mated with 18 females of the same lineage. On day 18 of pregnancy, females were euthanasied in a chamber of CO2 and after incision of the abdomen, the uterus was exposed. Then, resorptions as well as living and dead fetuses were evaluated, also the number of embryo/fetal implantation sites. Fetuses and their placenta were weighted to calculate the placental index. Three placentas of each litter were separated for microscopic analysis. RESULTS: Administration of the Meglumine Antimoniate did not interfere in the estral cycle of the treated group, since it did not alter the precoital interval and fertility index. Placenta alterations were not observed in the F2 generations. CONCLUSION: Meglumine Antimoniate did not interfere in the reproductive performance, after chronic exposition of dams. Data suggest that there is a gradual elimination of Meglumine Antimoniate by the maternal organism without damaging the future offspring.