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A precise and accurate liquid chromatography-tandem mass spectrometric (LC-MS/MS) bioanalytical method has been developed and validated for the simultaneous quantification of WCK 4234 and meropenem (MEM) in dog plasma. Protein precipitation using acetonitrile was employed as a sample preparation approach. Cefepime was used as an internal standard. The developed method was selective, sensitive (limit of quantification, 0.075 μg/ml for both drugs), accurate (recovery > 90%), precise (CV < 10%) and linear (r 2  ≥ 0.99, concentration range 0.075-120 μg/ml for both analytes). The developed method was successfully applied for the determination of both drugs in plasma to assess the pharmacokinetics in beagle dogs. WCK 4234 + MEM in a 1:1 ratio at 15 + 15 and 30 + 30 mg/kg doses were administered by the intravenous route. The mean plasma concentration and area under the concentration-time curve of WCK 4234 ranged from 38.3 to 77.4 μg/ml and from 47.8 to 77.1 μg h/ml, respectively, and the values for MEM ranged from 52.2 to 115.3 μg/ml and 70.5 to 133.6 μg h/ml respectively. The elimination half-life of WCK 4234 and MEM was around 0.8 h., (© 2022 John Wiley & Sons, Ltd.)

Background and Aim: The incidence of gastroesophageal reflux disease (GERD) is high after per-oral endoscopic myotomy (POEM). GERD after POEM may be qualitatively different from GERD in patients without motility disorders. In this study, we aimed to analyze and compare different aspects of GERD between patients with post-POEM GERD and nonachalasia GERD., Methods: The data of patients with GERD after POEM (January 2018 to June 2019) were compared with that of a control group (nonachalasia GERD group), which included patients presenting with typical reflux symptoms without associated major motility disorders. Patients with lower esophageal sphincter pressure lower than 10 mmHg were excluded from the study. GERD was evaluated at 3 months after POEM. Esophageal acid exposure time higher than 4.2% was used to define GERD. The primary outcome of the study was comparison of GERD-related quality of life and reflux symptom severity between the two groups. In addition, the severity of erosive esophagitis and reflux-symptom association were also recorded in the two groups., Results: A total of 100 patients were included in the study, with 50 patients in each group (post-POEM GERD vs. controls). The baseline parameters were comparable between the two groups. Median interquartile range of GERD-related quality of life score was significantly lower in the post-POEM group (11 [0-23.3] versus 34 [24-44]; p < 0.001). The post-POEM GERD group had significantly lower median heartburn (6.0 [0-16.3] versus 15.5 [7.5-24.8]; p = 0.001) and regurgitation scores (0 [0-6.0] versus 20.0 [12.3-25.0]; p < 0.001). Erosive esophagitis was more frequent in the post-POEM group (28 [56%] versus 10 [20.4%], p = 0.001). Only three (6%) patients in the post-POEM group had a positive reflux-symptom association as compared with 28 (56%) patients in the control group (p < 0.001)., Conclusion: In selected patients with pH positive GERD after POEM, the symptoms are milder and reflux-symptom association is poor in spite of more severe esophagitis as compared with controls., (© 2020 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

A precise and accurate liquid chromatography-tandem mass spectrometric (LC-MS/MS) bioanalytical method has been developed and validated for the simultaneous quantification of zidebactam (ZID) and cefepime (FEP) in dog plasma. Ceftazidime was used as an internal standard. Protein precipitation method was used as sample preparation approach. The calibration curve obtained was linear (r ≥ 0.99) over the concentration range 0.156-80 μg/mL for ZID and 0.312-160 μg/mL for FEP. The method was validated as per US Food and Drug Administration guidelines and the results met the acceptance criteria. A run time of 3.5 min for each sample made it possible to analyze the maximum number of samples per day. The proposed method was successfully applied for pharmacokinetic study in beagle dogs., (Copyright © 2018 John Wiley & Sons, Ltd.)