Aim of the studyThe subject of study was the stability of cisplatin in concentrate in glass vials and diluted in polyethylene (PE) bags stored at 15–25°C for up to 30 days.Material and methodsOriginal vials of cisplatin injection (1 mg/ml, Teva) were stored at room temperature and subjected to re-piercing after 1, 2, 3, 7, 14, 21, 28 and 30 days following the initial piercing. Cisplatin infusions at nominal concentrations of 0.1 mg/ml were prepared in 0.9% sodium chloride (1000 ml) in PE bags. Chemical stability was measured by means of a stability-indicating high-performance liquid chromatography (HPLC) assay. Physical stability was assessed by visual inspection in normal light.ResultsThe concentration of cisplatin at each sampling time in the analysed solutions remained within 92.0–100.7% of initial concentration, regardless of the container. No changes in colour or turbidity were observed in any of the vials or prepared solutions.ConclusionsCisplatin, both undiluted in glass containers and diluted with NaCl 0.9% in PE bags, remains stable (< 10% degradation) for at least 30 days at room temperature when protected from light.

In calixarenes hydrogen-bonded rings are present. One proton was removed from the four-and six-membered rings, respectively, by such strong bases as 1,3,4,6,7,8-hexahydro-1-methyl-2H-pyrimido[1,2-a]pyrimidine (MTBD) and phosphazene (P 2 Et), respectively. In the FT-IR spectra of acetonitrile solutions in which these deprotonated molecules are present, intense continua are observed, demonstrating that these negatively charged rings show large proton polarizability due to collective proton fluctuation. These proton polarizabilities increase with increasing size of the rings. This latter result is in good agreement with our earlier theoretical treatments.

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Background Diabetes reduces the activity of CYP3A4 and may increase the exposure for the drugs metabolized by the isoenzyme. Sorafenib is a multi-targeted tyrosine kinase inhibitor (TKI), used for the treatment of advanced renal cell carcinoma, hepatocellular carcinoma and radioactive iodine resistant thyroid carcinoma. The TKI undergoes CYP3A4-dependent oxidative transformation, which may be influenced by hyperglycaemia. The aim of the study was to compare the oxidation for sorafenib between healthy and streptozotocin-induced diabetic rats. Additionally, the effect of sorafenib on glucose levels was investigated. Methods The rats were assigned to the groups: streptozotocin-induced diabetic (DG, n = 8) or healthy (HG, n = 8). The rats received sorafenib orally as a single dose of 100 mg/kg. The plasma concentrations of sorafenib and its metabolite N-oxide were measured with the validated high-performance liquid chromatography with ultraviolet detection. Results The difference between groups in Cmax and AUC0−t values for sorafenib were significant (p = 0.0004, p = 0.0104), and similarly for the metabolite (p = 0.0008, p = 0.0011). Greater exposure for the parent drug and analysed metabolite was achieved in diabetic group. However, the Cmax, AUC0−t, and AUC0−∞ ratios between the metabolite and sorafenib were similar in both groups. The significant reduction of glycaemia was observed only in the diabetic animals. Conclusion The findings of the study provide evidence that diabetes significantly influence on the exposition for sorafenib and its metabolite, but similar ratios N-oxide/sorafenib for AUC and Cmax in healthy and diabetic animals suggest that oxidation of the TKI is rather unchanged. Additionally, sorafenib-associated hypoglycaemia was confirmed in diabetic animals.