A VALIDATED LC-MS/MS METHOD FOR PHARMACOKINETIC STUDY OF CANAGLIFLOZIN IN HEALTHY RABBITS

Objective: A liquid chromatography-tandem mass spectrophotometric (LC-MS/MS) method was developed for quantification of canagliflozin in rabbit plasma employing Liquid-Liquid extraction technique.Methods: Chromatographic separation was achieved on Inertsil ODS 5 µm C18, 50×4.60 mm with 30:70 v/v of 0.01M ammonium acetate: methanol as an isocratic mobile phase with a flow rate of 0.8 ml/min. The developed LC-MS method was applied to assess Cmax, t1/2, AUC0-t, and AUC0-inf of canagliflozin tablet after oral administration in healthy rabbits.Results: The developed method was linear over working range of 5ng/ml to 600ng/ml with a coefficient of correction (r2) = 0.999. The % recovery of the method was found to be 102.05%. The mean intraday and inter-day precision of the method was found to be 0.77 to 3.72%. The Canagliflozin showed Tmax of 1.58±0.2 and mean Cmax, AUC0®t andAUC0®a for Test formulation is 272±13.24, 2571.20±251and 2777.43±276 respectively.Conclusion: The developed method can be applied for routine analysis for quality control and the established LLOQ is sufficiently low to conduct a pharmacokinetic study with any marketing formulation of Canagliflozin in healthy rabbits

A UPLC-MS/MS METHOD DEVELOPMENT AND VALIDATION FOR THE ESTIMATION OF SOFOSBUVIR FROM HUMAN PLASMA

Objective: The present work aimed to develop a simple, rapid, specific and precise ultra-performance liquid chromatography-tandem mass spectrophotometric (LC–MS/MS) validated method for quantification of sofosbuvir and internal standard (ISTD) Sofosbuvir-d3 in human plasma.Methods: Samples prepared by employing liquid-liquid extraction (LLE) using 2.5 ml of ethyl acetate. Chromatographic separation was achieved on Gemini 5µ C18, 50 x 4.6 mm column using a mixture of 0.1% (v/v) formic acid in water to methanol at a ratio of 30:70 v/v as the mobile phase. The flow rate was 0.50 ml/min. The LC eluent was split, and approximately 0.1 ml/min was introduced into Tandem mass spectrometer using turbo Ion Spray interface at 325 °C. Quantitation was performed by transitions of 428.35/279.26 (m/z) for sofosbuvir and 431.38/282.37 (m/z) for sofosbuvir-d3.Results: The concentrations of ten working standards showed linearity between 4.063 to 8000.010ng/ml (r2 ≥ 0.9985). Chromatographic separation was achieved within 2 min. The average extraction recoveries of three quality control concentrations were 75.36% for sofosbuvir and were within the acceptance limits. The coefficient of variation was ≤15% for intra-and inter-batch assays. The %CV of ruggedness ranges 0.35% and 3.09%. The % stability of short term and long term stock solution stability studies was found to be 97.25% and 98.81% respectively.Conclusion: The results obtained for specificity, linearity, accuracy, precision, ruggedness and stability studies were within the acceptance limits. Thus the validated economical method was applied for pharmacokinetic studies of sofosbuvir

Pseudomonas septicaemia: in a case of pancytopenia

Pseudomonal infection is a rare condition with multiple systemic complications. A new condition of interest is ecthyma gangrenosum in a patient with pseudomonas septicaemia with pancytopenia and megaloblastic anaemia. So here we present you the case of Ecthyma gangrenosum in a 20-year-old female with pseudomonas septicaemia due to pancytopenia. A high degree of clinical suspicion is required, but a tissue sample is ultimately necessary for definitive diagnosis

Sentiment Analysis on IMDb Movie Reviews Using Hybrid Feature Extraction Method

Social Networking sites have become popular and common places for sharing wide range of emotions through short texts. These emotions include happiness, sadness, anxiety, fear, etc. Analyzing short texts helps in identifying the sentiment expressed by the crowd. Sentiment Analysis on IMDb movie reviews identifies the overall sentiment or opinion expressed by a reviewer towards a movie. Many researchers are working on pruning the sentiment analysis model that clearly identifies and distinguishes between a positive review and a negative review. In the proposed work, we show that the use of Hybrid features obtained by concatenating Machine Learning features (TF, TF-IDF) with Lexicon features (Positive-Negative word count, Connotation) gives better results both in terms of accuracy and complexity when tested against classifiers like SVM, Naïve Bayes, KNN and Maximum Entropy. The proposed model clearly differentiates between a positive review and negative review. Since understanding the context of the reviews plays an important role in classification, using hybrid features helps in capturing the context of the movie reviews and hence increases the accuracy of classification

Glucosamine HCl-based solid dispersions to enhance the biopharmaceutical properties of acyclovir

The objective of the work presented here was to assess the feasibility of using glucosamine HCl as a solid-dispersion (SD) carrier to enhance the biopharmaceutical properties of a BCS class III/IV drug, acyclovir (ACV). The solid-dispersions of acyclovir and glucosamine HCl were prepared by an ethanol-based solvent evaporation method. The prepared formulations characterized by photomicroscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transforms infrared spectrophotometry (FTIR), powder x-ray diffractometry (PXRD) and drug content analysis. The functional characterization of ACV-SD was performed by aqueous solubility evaluation, dissolution studies, fasted versus fed state dissolution comparison, ex vivo permeability, and stability studies. Photomicroscopy and SEM analysis showed different surface morphologies for pure ACV, glucosamine HCl and ACV-SD. The physical-chemical characterization studies supported the formation of ACV-SD. A 12-fold enhancement in the aqueous solubility of ACV was observed in the prepared solid dispersions, compared to pure ACV. Results from in vitro dissolution demonstrated a significant increase in the rate and extent of ACV dissolution from the prepared ACV-SD formulations, compared to pure ACV. The rate and extent of ACV permeability across everted rat intestinal membrane were also found to be significantly increased in the ACV-SD formulations. Under fed conditions, the rate and extent of the in vitro dissolution of ACV from the formulation was appreciably greater compared to fasted conditions. Overall, the results from the study suggest the feasibility of utilizing glucosamine HCl as a solid dispersion carrier/excipient for enhancement of biopharmaceutical properties of acyclovir, and similar drugs with low solubility/permeability characteristics

Comparison Of Serum Lipid Levels In Periodontal Health And Disease In Systemically Healthy Subjects – A Clinical And Biochemical Study

Aim: To compare the serum lipid levels in systemically healthy subjects with and without periodontal disease and to correlate the results between hyperlipidemia and periodontitis.  Material and Methods: A total of 80 subjects of both sexes (42 males and 38 females), in the age group of 35-55 yrs were divided into two groups of 40 each as study and controls. All the patients were evaluated for serum cholesterol, serum triglycerides, LDL and HDL cholesterol. Variables related to high cholesterol levels, including age, sex and body mass index were also evaluated. The dental parameters recorded consisted of probing pocket depth (PPD), community periodontal index (CPI) and periodontal disease index (PDI).   Results: Total cholesterol, LDL cholesterol and triglycerides were marginally increased in study group but were not found to be statistically significant (p=0.106, p=0.100 & p=0.199 respectively). Triglycerides showed a positive correlation with CPI and PDI after adjusting for age and disease. However, the correlation of triglycerides with PDI was minimal compared to the correlation of triglyceride with CPI.  Conclusion: The findings of this study showed that there was no significant relationship between periodontal disease, regardless of its intensity, and blood lipid levels in the study population

Prediction of peptidoglycan hydrolases- a new class of antibacterial proteins

Comparison of performance of the three approaches using known 250 peptidoglycan hydrolases. (XLSX 8 kb

A radiologic analysis: Relationships of the thoracic spine to aid palpation of the thoracic transverse processes

Introduction: In the field of osteopathic manipulative medicine, palpation is an important skill used by physicians to localize structures to diagnose and treat patients with somatic dysfunction throughout the musculoskeletal system. Specifically, in the thoracic spine, physicians can use the more superficial spinous process of each vertebra to assist in locating the deeper, more challenging to palpate, transverse process of the vertebra. Historically, the “rule of threes”, proposed by Mitchell et al in 1979, describing the relationships between spinous processes and transverse processes of the thoracic spine has been taught in osteopathic medical schools. However, another model was more recently proposed by Geelhoed et al in 2006. To our knowledge, these models have never been analyzed radiologically using computed tomography in patients. Objectives: To evaluate the accuracy of several proposed models, including the rule of 3’s and Geelhoed’s rule, which aid in palpation of the transverse processes of the thoracic spine based on their relation to the spinous processes. Furthermore, the study aims to analyze the intervertebral and intravertebral relationships of the transverse processes and spinous processes of the thoracic spine. Methods: This was an observational study with retrospective analysis of high-resolution computed tomography of the chest in the prone position. Four measurements were taken per thoracic vertebra in the coronal plane during inspiration. Based on the measurements, it was determined whether each individual vertebra followed the models or not. The measurements were further analyzed to define additional intervertebral and intravertebral relationships between the transverse and spinous processes of the thoracic spine. Results: We predict that the high-resolution computed tomography will reveal the intervertebral and intravertebral relationships as well as the aid in defining the accuracy of the relationships between the spinous processes proposed in osteopathic manipulative models. Conclusion: We conclude that retrospective radiological studies using state of the art images has the ability to confirm and/or expand our ability to utilize osteopathic principles and models in diagnosing and treating patients