Application of differential scanning calorimetry in the analysis of apprehended formulations of anabolic androgenic steroids.

Over the past ten years, there has been a significant increase in the amount of formulations containing anabolic androgenic steroids apprehended worldwide. A considerable amount of these illicit preparations is falsified imposing a series of challenges for the analytical identification of alleged active ingredients due to the presence of interferers. In this sense, the aim of this work was to identify and quantify the active ingredient using cholesterol as internal standard in eight apprehended formulations of anabolic androgenic steroids in either tablet, capsule or injectable forms employing visual inspection and instrumental analysis of Fourier Transform Infrared Spectroscopy, Gas Chromatography - Mass Spectrometry and Differential Scanning Calorimetry. The assessed samples were kindly provided by the Brazilian Federal Police as representative samples from an apprehension made in July of 2017. Qualitatively, 25% of the analyzed materials were determined to be falsified as they were composed of excipients only while the others had the alleged active ingredient confirmed. However, after quantitative analysis, the majority of samples were placed as counterfeit materials as the active substance was found in concentrations lower than stated in the label. Preliminary visual inspection provided important information to distinguish genuine from falsified samples. It should be noted that this work was one of the few available reports to employ Differential Scanning Calorimetry in the analysis of anabolic agents, which proved to be an important complementary tool for the detection of the active ingredient, when present, along with the calorimetric profile of the formulations studied. Fourier Transform Infrared Spectroscopy and Gas-Chromatography - Mass Spectrometry were also efficient analytical tools in order to identify and to characterize substances present in fraudulent preparations.

Antitumor potential of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H-pyrazoles in human bladder cancer cells.

Bladder cancer is a genitourinary malignant disease common worldwide. Current chemotherapy is often limited mainly due to toxicity and drug resistance. Thus, there is a continued need to discover new therapies. Recently evidences shows that pyrazoline derivatives are promising antitumor agents in many types of cancers, but there are no studies with bladder cancer. In order to find potent and novel chemotherapy drugs for bladder cancer, a series of pyrazoline derivatives 2a-2d were tested for their antitumor activity in two human bladder cancer cell lines 5647 and T24. The MTT assay showed that the compounds 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-1H-pyrazole (2a) and 1-thiocarbamoyl-5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole (2c) decrease the cell viability of 5637 cells. Molecular modeling indicated that these compounds had a good oral bioavailability and low toxicities. Clonogenic assay and flow cytometric analysis were used to assess colony formation, apoptosis induction and cell cycle distribution. Overall, our results suggest that pyrazoline 2a and 2c, with the substituents hydrogen and chlorine respectively, may decrease cell viability and colony formation of bladder cancer 5637 cell line by inhibition of cell cycle progression, and for pyrazoline 2a, by induction of apoptosis. As indicated by the physicochemical properties of these compounds, the steric factor influences the activity. Therefore, these pyrazoline derivatives can be considered promising anticancer agents for the treatment of bladder cancer.