Investigation of Pharmacokinetic Parameters of Trelagliptin in Egyptian Volunteers Using Sensitive LC-MS/MS: A Comparative Study with a Japanese Population

Trelagliptin (TLN) is a novel once-weekly antidiabetic drug that enhanced the patient compliance in type 2 diabetes. TLN analysis and bioanalysis literature review showed many methods for TLN assay either in dosage form or as biological fluids (pharmacokinetic parameters), but all those methods did not consider the full details dealing with biological assay of TLN. Studies that included information about pharmacokinetic parameters did not mention the used analytical procedures for those determinations and parameters. Although some LC-MS/MS and UPLC-UV methods were reported for TLN bioassay in rats’ plasma, they used direct precipitation techniques, and the current described procedure showed lower LLOQ than all the reported methods in spite of that working on human plasma is more complicated than on rats’ plasma. In this study, LC-MS/MS bioanalysis of TLN in human plasma (4–1000 nM) was employed successfully with LLOQ of 4 nM which is lower than all reported methods in rats’ plasma followed by a preliminary pharmacokinetic study. Alogliptin was used as internal standard (IS) because of its structure similarity to TLN. Pharmacokinetic parameters of TLN were investigated in Egyptian volunteers, and they had been compared to Japanese. Liquid-liquid extraction showed more sensitive results than direct precipitation. The proposed method was successfully applied to a pharmacokinetic study conducted on Egyptian volunteers. No dose modification is required upon comparing the pharmacokinetic parameters of the current study and previous studies on non-Egyptian volunteers.

Comparative Bioavailability and Pharmacokinetics Between the Solid Form of Metformin vs a Novel Liquid Extemporaneous Formulation in Children

Metformin pharmacokinetics in a liquid extemporaneous formulation from commercial tablets was determined in paediatric patients. A randomized, transversal clinical trial was conducted in 34 children and adolescents between 7 and 17 years of age. 17 children were randomized to take metformin in the liquid formulation and, after a 1-week wash period, a 500 mg metformin tablet was administered to them. Blood samples were obtained in Whatman 903® cards at 0, 1, 2, 4, 8, 12 and 24 hours. Extraction was made by direct precipitation with acetonitrile (ACN) and methanol, detection by UPLC and tandem mass spectrometry. The method was accurate, precise, selective and linear from 50 to 1000 ng/mL (r = .9982). Comparative pharmacokinetics, tablet vs formulation, were as follows: Cmax 1503.2 ng/mL vs 1521.4, Tmax 1.5 h vs 2.3, and half-life 8.2 vs 7.5 h. The liquid formulation of metformin showed similar pharmacokinetics to the tablet, and the ratios (90% CI) of geometric mean for metformin were 100.63% (89.13–113.6), 98.08% (88.04–109.2), and 97.52% (84.9–112.01), for Cmax, AUC0-t, and AUC 0-∞, respectively. Pharmacokinetics was determined using WinNonlin Pro 3.1 software. The liquid formulation of metformin showed similar pharmacokinetics to the tablet, allowing a more precise dose adjustment and ease of administration.

Manipulating the Morphology of a Metal-Organic Framework: UiO-66

Metal-Organic Frameworks (MOFs) are an emerging group of crystalline microporous materials that exhibit tunability towards various applications in gas storage, catalysts, and others. This project investigated the effects of reaction variables on UiO-66 via solvothermal synthesis. The results via the direct precipitation route at producing UiO-66 suggested that the crystallization rate was rather stagnant during the 30-day synthesis time, rendering the room temperature synthesis infeasible. Subsequently, the project investigated the effects of stirring time of the reactants for the first time in solvothermal synthesis, temperature, reaction time, modulator ratio, and reactant concentrations, on the morphology of UiO-66. Finally, the project studied the effects of adding glycols as co-solvents on UiO-66 crystal morphology. It was observed that only using ethylene glycol as a co-solvent successfully reformed the morphology of UiO-66 crystals from rounded octahedral crystals to anisotropic needle-like fibers. The results also indicated that diethylene glycol significantly improved the crystallinity of UiO-66 than triethylene glycol did.

Manipulating the Morphology of a Metal-Organic Framework: UiO-66

Metal-Organic Frameworks (MOFs) are an emerging group of crystalline microporous materials that exhibit tunability towards various applications in gas storage, catalysts, and others. This project investigated the effects of reaction variables on UiO-66 via solvothermal synthesis. The results via the direct precipitation route at producing UiO-66 suggested that the crystallization rate was rather stagnant during the 30-day synthesis time, rendering the room temperature synthesis infeasible. Subsequently, the project investigated the effects of stirring time of the reactants for the first time in solvothermal synthesis, temperature, reaction time, modulator ratio, and reactant concentrations, on the morphology of UiO-66. Finally, the project studied the effects of adding glycols as co-solvents on UiO-66 crystal morphology. It was observed that only using ethylene glycol as a co-solvent successfully reformed the morphology of UiO-66 crystals from rounded octahedral crystals to anisotropic needle-like fibers. The results also indicated that diethylene glycol significantly improved the crystallinity of UiO-66 than triethylene glycol did.