A single LC-MS/MS validated method for tulathromycin quantification in plasma, seminal plasma, and urine to be applied in a pharmacokinetic study in bull

Tulathromycin is a macrolide antibiotic generally used for the treatment of respiratory diseases in cattle and swine. This work proposes an improvement of a previously published LC-MS/MS method for tulathromycin determination in pig serum, here validated in three different bull matrices: plasma, seminal plasma, and urine. The approach is based on a quick protein precipitation with acetonitrile, filtration, and sample dilution before injection, allowing to rapidly process large batches of samples. Analytes separation was obtained using a BEH C18 (50 x 2.1 mm, 1.7 mu m) column, maintained at 40 degrees C with a chromatographic run of 5 min. The method was fully validated over concentration ranges suitable for field levels of tulathromycin found in each matrix (0.01-1 mu g/ml for plasma, 0.05-5 mu g/ml for seminal plasma, and 0.1-10 mu g/m1 for urine), showing good linearity during each day of testing (R-2 always >0.99). Accuracy and precision were within +/- 15% at all QC concentrations in all the three matrices. Furthermore, the use of tulathromycine-d7 as internal standard mitigated the potential impacts of matrix effect. The validated technique was successfully applied to samples collected during a pharmacokinetic study in bulls, allowing to monitor tulathromycin concentrations over time in the three matrices. To our knowledge, this is the first validated approach for LC-MS/MS quantification of tulathromycin in seminal plasma and urine

Plasma Concentration Rise after the Intramuscular Administration of High Dose Medetomidine (0.13 mg/kg) for Semen Collection in Cats

High dose medetomidine 0.13 mg/kg can be used for semen collection in cats with variable results in terms of quantity and quality. Therefore, a variation in terms of distribution and elimination among patients has been hypothesised. The aim of the study was to characterise the pharmacokinetics of medetomidine (0.13 mg/kg) administered intramuscularly (IM) in healthy male cats. Eighteen male cats undergoing castration were included, and medetomidine (0.13 mg/kg) was administered IM. Venous blood samples were collected at 20, 30, 40, 50, 60, 75 and 90 minutes after medetomidine administration. Before orchiectomy, at T20, sperm collection was attempted. Plasma medetomidine concentrations were determined by liquid chromatography/mass spectrometry analysis. Semen collection was successful in 15/18 cats. The medetomidine plasma concentration following the IM administration of a bolus was best described using a non-compartment model. Time of maximum concentration was observed at 40 minutes (range 20-90); maximum concentration was 32.8 ng/mL (range 26.8-51.2). The median apparent clearance was 11.9 mL/kg/minute (range 0.7-43.8). In conclusion, medetomidine administered IM at 0.13 mg/kg reached its peak plasma concentration slowly and with variability among patients. In addition, it was characterised by low total body clearance probably due to the cardiovascular alterations associated with medetomidine administration

An LC-MS/MS method for the determination of budesonide and 16α-hydroxyprednisolone in dog plasma

open6noAlthough budesonide is frequently used in veterinary medicine for the treatment of canine respiratory and bowel inflammatory diseases, knowledge is lacking regarding its kinetics in this species. We developed and validated a liquid chromatography–tandem mass spectrometry method for the determination of budesonide and its metabolite 16a-hydroxyprednisolone in dog plasma. The analytes were extracted by solid phase extraction and analysis was performed by high performance liquid chromatography–tandem mass spectrometry, with positive electrospray ionization. This method allows budesonide and one of its main metabolites to be simultaneously quantified in dog plasma at fairly low concentrations. The proposed protocol is very easy and fast to execute, without compromising analytical performances. A small amount (0.5mL) of plasma is required, making this approach suitable for pharmacokinetic studies also in small sized dogs.openGazzotti, Teresa; Barbarossa, Andrea; Zironi, Elisa; Roncada, Paola; Pietra, Marco; Pagliuca, GiampieroGazzotti, Teresa; Barbarossa, Andrea; Zironi, Elisa; Roncada, Paola; Pietra, Marco; Pagliuca, Giampier

Assessment of perfluorooctane sulfonate and perfluorooctanoic acid exposure through fish consumption in Italy

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are pollutants of anthropic origin with possible side effects on human health. Diet, and in particular fish and seafood, is considered the major intake pathway for humans. The present study investigated the levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) contamination in twenty-five samples of fresh fillet of five widely consumed fish species purchased from large retailers in Italy, to be used for an estimation of the Italian population exposure to these contaminants. PFOS and PFOA were found in all samples, at concentrations up to 1,896 (mean = 627 ng/kg) and 487 ng/kg (mean = 75 ng/kg), respectively, confirming the role of fish as high contributor to human exposure. However, a remarkable inter-species variability was observed, and multiple factors were suggested as potentially responsible for such differences, suggesting that the preferential consumption of certain species could likely increase the intake, and thus the exposure. The exposure estimates for both average and high fish consumers resulted far below the TDIs for PFOS and PFOA in all age groups, confirming the outcomes of EFSA\u2019s scientific report. In particular, the calculated total dietary exposure for the 95th percentile consumers belonging to the toddler age class, the most exposed group, resulted equal to 9.72 ng/kg b.w./day for PFOS and 8.39 ng/kg b.w./day for PFOA

Enantiospecific pharmacokinetics of intravenous dexmedetomidine in beagles.

The goal of this study was to investigate the pharmacokinetic (PK) behaviour of dexmedetomidine in dogs administered as a pure enantiomer versus as part of a racemic mixture. Eight unmedicated intact purpose-bread beagles were included. Two intravenous treatments of either medetomidine or dexmedetomidine were administered at 10- to 14-day intervals. Atipamezole or saline solution was administered intramuscularly 45 min later. Venous blood samples were collected into EDTA collection tubes, and the quantification of dexmedetomidine and levomedetomidine was performed by chiral LC-MS/MS. All dogs appeared sedated after each treatment without complication. Plasma concentrations of levomedetomidine were measured only in the racemic group and were 51.4% (51.4%-56.1%) lower than dexmedetomidine. Non-compartmental analysis (NCA) was performed for both drugs, while dexmedetomidine data were further described using a population pharmacokinetic approach. A standard two-compartment mammillary model with linear elimination with combined additive and multiplicative error model for residual unexplained variability was established for dexmedetomidine. An exponential model was finally retained to describe inter-individual variability on parameters of clearance (Cl1 ) and central and peripheral volumes of distribution (V1 , V2 ). No effect of occurrence, levomedetomidine or atipamezole could be observed on dexmedetomidine PK parameters. Dexmedetomidine did not undergo significantly different PK when administered alone or as part of the racemic mixture in otherwise unmedicated dogs

Determination of Commercial Animal and Vegetable Milks’ Lipid Profile and Its Correlation with Cell Viability and Antioxidant Activity on Human Intestinal Caco-2 Cells

none9openantonella aresta; Stefania De Santis; Alessia Carocci; Alexia Barbarossa; Andrea Ragusa; Nicoletta De Vietro; Maria Lisa Clodoveo; Filomena Corbo; Carlo ZAMBONINAresta, Antonella; De Santis, Stefania; Carocci, Alessia; Barbarossa, Alexia; Ragusa, Andrea; De Vietro, Nicoletta; Lisa Clodoveo, Maria; Corbo, Filomena; Zambonin, Carl