Alptug Atila

Preparation and characterization of metformin hydrochloride loaded-Eudragit®RSPO and Eudragit®RSPO/PLGA nanoparticles

The aim of the present study was to develop and characterize metformin HCl-loaded nanoparticle formulations. Nanoparticles were prepared by the nanoprecipitation method using both a single polymer (Eudragit®RSPO) and a polymer mixture (Eudragit/PLGA). The mean particle size ranged from 268.8 to 288 nm and the nanoparticle surface was positively charged (9.72 to 10.1 mV). The highest encapsulation efficiency was observed when Eudragit®RSPO was used. All formulations showed highly reproducible drug release profiles and the in vitro drug release in phosphate buffer (pH = 6.8) ranged from 92 to 100% in 12 h. These results suggest that Eudragit®RSPO or Eudragit/PLGA nanoparticles might represent a promising sustained-release oral formulation for metformin HCl, reducing the necessity of repeated administrations of high doses to maintain effective plasma concentrations, and thus, increasing patient compliance and reducing the incidence of side-effects.

Development and validation of UFLC-MS/MS method for determination of bosentan in rat plasma.

A rapid, simple and sensitive UFLC-MS/MS method was developed and validated for the determination of bosentan in rat plasma using etodolac as an internal standard (IS) after liquid-liquid extraction with diethyl ether-chloroform (4:1, v/v). Bosentan and IS were detected using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the transitions m/z 551.90→201.90 and 288.20→172.00, respectively. Chromatographic separation was performed on the inertsil ODS-4 column with a gradient mobile phase, which consisted of 0.1% acetic acid with 5mM ammonium acetate in water for solvent A and 5mM ammonium acetate in acetonitrile-methanol (50:50, v/v) for solvent B at a flow rate of 0.3mL/min. The method was sensitive with 0.5ng/mL as the lower limit of quantitation (LLOQ) and the standard calibration curve for bosentan was linear (r>0.997) over the studied concentration range (0.5-2000ng/mL). The proposed method was fully validated by determining specificity, linearity, LLOQ, precision and accuracy, recovery, matrix effect and stability. The validated method was successfully applied to plasma samples obtained from rats.

Phtytochemical Studies and Quantitative HPLC Analysis of Rosmarinic Acid and Luteolin 5- O -β-D-Glucopyranoside on Thymus praecox subsp. grossheimii var. grossheimii

Thymus praecox ssp. grossheimii (RONNIGER) JALAS var. grossheimii (Lamiaceae) is used as an herbal tea for cold, stomachache, cough, and infections in Turkey. There are no phytochemical studies on this species. We performed phytochemical studies and quantitative analysis of rosmarinic acid and luteolin 5-O-β-D-glucopyranoside in the methanol extract of the plant. Several chromatographic methods were used for the isolation of major compounds. HPLC methods were applied for quantitative analysis of rosmarinic acid and luteolin 5-O-β-D-glucopyranoside in the methanol extract. In this study, ursolic acid (1), oleanolic acid (2), methyl rosmarinate (3), ethyl rosmarinate (4), rosmarinic acid (5), luteolin 5-O-β-D-glucopyranoside (6), and thymoquinol 2,5-O-β-diglucopyranoside (7) were isolated from the aerial parts of the plant. The relative contents of rosmarinic acid and luteolin 5-O-β-D-glucopyranoside in the extract were 15.2 and 57.8 mg/g of dry weight, respectively. Compounds isolated from this plant and the contents of rosmarinic acid and luteolin 5-O-β-D-glucopyranoside provided reasonable evidence for the traditional usages of this plant.

Pharmacokinetics of florfenicol in the plasma of Japanese quail

Abstract AIM: To determine the pharmacokinetics and bioavailability of florfenicol in the plasma of healthy Japanese quail (Coturnix japonica). METHODS: Sixty-five quail were given an I/V and I/M dose of florfenicol at 30 mg/kg bodyweight (BW). A two-period sequential design was used, with a wash-out period of 2 weeks between the different routes of administration. Concentrations of florfenicol in plasma were determined using high-performance liquid chromatography (HPLC). RESULTS: A naíve pooled data analysis approach for the plasma concentration-time profile of florfenicol was found to fit a non-compartmental open model. After I/V administration, the mean residence time (MRT), mean volume of distribution at steady state (Vss), and total body clearance of florfenicol were 12.0 (SD 0.37) h, 8.7 (SD 0.22) L/kg, and 1.3 (SD 0.08) L/h/kg, respectively. After I/M injection, the MRT, mean absorption time (MAT), and bioavailability were 12.3 (SD 0.37) h, 0.2 (SD 0.02) h, and 79.1 (SD 1.79)%, respectively. CONCLUSIONS: The time for the concentration of florfenicol to fall below the probable effective concentration of 1 µg/ml of approximately 10 h is sufficient for the minimum inhibitory concentration needed for many bacterial isolates. Further pharm acodynamic studies in quail are needed to evaluate a suitable dosage regimen.

Study of the boron levels in serum after implantation of different ratios nano-hexagonal boron nitride-hydroxy apatite in rat femurs.

Boron and its derivatives are effective in bone recovery and osteointegration. However, increasing the boron levels in body liquids may cause toxicity. The aim of our study is to investigate serum boron levels using ICP-MS after implantation of different ratios of nano-hBN-HA composites in rat femurs. All rats were (n=126) divided into five experimental groups (n=24) and one healthy group (6 rats); healthy (Group1), femoral defect + %100 HA (Group2), femoral defect + %2.5 hBN + %97.5 HA (Group3), femoral defect + %5 hBN + %95 HA (Group4), femoral defect + %10 hBN + %90 HA (Group5), femoral defect + %100 hBN (Group6). The femoral defect was created in the distal femur (3mm drill-bit). Each implant group was divided into four different groups (n=24) also 6 rats sacrificed for each groups in one week intervals during four weeks. In our results; at 1, 2, 3, and 4 weeks after implantation near bone tissue, serum levels of boron were evaluated using ICP-MS. We demonstrated that neither short-term nor long-term implantation of hBN-HA composite resulted in statistically increased serum boron levels in experimental groups compared to healthy group. In conclusion, this study investigated the implant material produced form hBN-HA for the first time. Our data suggest that hBN is a new promising target for biomaterial and implant bioengineers.

Rapid and sensitive UPLC-MS/MS method for the determination of etodolac in small-volume rat plasma: Application to rat real samples

Abstract A rapid, simple, and sensitive UPLC-MS/MS method was developed and validated for the determination of etodolac in rat plasma using flurbiprofen as an internal standard (IS). Etodolac and IS were detected using electrospray ionization in negative ion multiple reaction monitoring mode by monitoring the transitions (precursor to product) m/z 286.2→212.1 and 243.2→199.2, respectively. The developed new extraction procedure for etodolac in rat plasma does not contain more than one stage. Chromatographic separation was performed on reverse phase C18 column with a gradient mobile phase, which consisted of methanol for solvent A and 5 mM ammonium formate in water solvent B percentages varying at a flow rate of 0.4 mL/min. The LLOQ for etodolac was determined as 1 ng/mL. The calibration curve for etodolac was linear (r > 0.996 for plasma) well within the range of 1–5000 ng/mL. Quantification of etodolac in rat plasma is possible in a short chromatographic run time (1.91 min) with this method. The proposed method was fully validated by determining specificity, linearity, LLOQ, precision and accuracy, recovery, matrix effect, and stability. The validated method was successfully applied to plasma samples obtained from rats. Graphical Abstract