Microscopic and Biopharmaceutical Evaluation of Emulsion and Self-Emulsifying Oil with Cyclosporine.

Among the currently available commercial eye drops with cyclosporine A (Cs) there is a lack of long-acting dosage forms and products with a concentration of the drug substance higher than 0.1%, although Cs is widely used in ophthalmology. The aim of the research was to conduct the microscopic and biopharmaceutical evaluation of two formulations, an emulsion (EM) and a self-emulsifying oil (SEO), both with 0.

Reversed-phase pH gradient thin-layer chromatography of biologically active substances with controlled developing solvent velocity.

For the first time, stepwise pH gradient thin-layer chromatograms of biologically active substances with controlled developing solvent velocity are presented and described in the paper. Change in buffer pH of the mobile phase solution influences retardation, selectivity, and shape of the separated substances' spots. The conducted research has confirmed that the mobile phase's pH gradient could be an essential factor to optimize the conditions of the separation of substances in reversed-phase high-performance thin-layer chromatography.

The Characterization of Ground Raspberry Seeds and the Physiological Response to Supplementation in Hypertensive and Normotensive Rats.

This study aimed to evaluate the protective role of ground raspberry seeds (RBS) as a source of polyphenols and essential fatty acids on blood plasma enzymatic antioxidant status, lipid profile, and endothelium-intact vasodilation during physiological and pathological conditions. Young normotensive Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) at ten weeks of age were fed with either a control diet or were supplemented with added 7% RBS for six weeks ( = 6). The main component of RBS was dietary fiber (64%) and the main polyphenols were ellagitannins (1.

Metabolomic Signature of Early Vascular Aging (EVA) in Hypertension.

Arterial stiffening is a hallmark of early vascular aging (EVA) syndrome and an independent predictor of cardiovascular morbidity and mortality. In this case-control study we sought to identify plasma metabolites associated with EVA syndrome in the setting of hypertension. An untargeted metabolomic approach was used to identify plasma metabolites in an age-, BMI-, and sex-matched groups of EVA ( = 79) and non-EVA ( = 73) individuals with hypertension.

Bayesian multilevel model of micro RNA levels in ovarian-cancer and healthy subjects.

In transcriptomics, micro RNAs (miRNAs) has gained much interest especially as potential disease indicators. However, apart from holding a great promise related to their clinical application, a lot of inconsistent results have been published. Our aim was to compare the miRNA expression levels in ovarian cancer and healthy subjects using the Bayesian multilevel model and to assess their potential usefulness in diagnosis.

Urinary metabolomic signature of muscle-invasive bladder cancer: A multiplatform approach.

Bladder cancer (BCa) is ninth amongst the most common types of cancer in the human population worldwide. The statistics of incidence and mortality of BCa are alarming and the currently applied diagnostic methods are still not sensitive enough. This leads to a large number of undiagnosed BCa cases, usually among patients in the early stages of the disease.

Column Characterization and Selection Systems in Reversed-Phase High-Performance Liquid Chromatography.

Reversed-phase high-performance liquid chromatography (RP-HPLC) is the most popular chromatographic mode, accounting for more than 90% of all separations. HPLC itself owes its immense popularity to it being relatively simple and inexpensive, with the equipment being reliable and easy to operate. Due to extensive automation, it can be run virtually unattended with multiple samples at various separation conditions, even by relatively low-skilled personnel.

Analysis of Isocratic-Chromatographic-Retention Data using Bayesian Multilevel Modeling.

The objective of this work was to develop a multilevel (hierarchical) model based on isocratic-reversed-phase-high-performance-chromatographic data collected in methanol and acetonitrile for 58 chemical compounds. Such a multilevel model is a regression model of the analyte-specific chromatographic measurements, in which all the regression parameters are given a probability model. It is a fundamentally different approach from the most common approach, where parameters are separately estimated for each analyte (without sharing information across analytes and different organic modifiers).

Targeted metabolomics in bladder cancer: From analytical methods development and validation towards application to clinical samples.

Bladder cancer constitutes the ninth most common cancer worldwide and, despite continuous development of new diagnostic approaches, the thirteenth leading cause of global cancer mortality. In our previous untargeted urine metabolomic investigation, seventeen metabolites were found to be statistically differentiating bladder cancer patients and healthy volunteers. Therefore, the main goal of this study was to develop and validate an analytical method for simultaneous quantitative determination of those metabolites using reversed phase high-performance liquid chromatography coupled with triple quadrupole mass spectrometry technique (RP-HPLC-QQQ/MS).

Ocular irritation and cyclosporine A distribution in the eye tissues after administration of Solid Lipid Microparticles in the rabbit model.

The aim of this study was to investigate the in vivo effect of Solid Lipid Microparticles (SLM), proposed for topical ocular administration of cyclosporine, on the rabbit eye. SLM carrier is an aqueous dispersion of lipid microparticles (20% w/w) with a size up to 15 μm. Cyclosporine was dissolved in the formulation in the concentration of 0.

Free silanols and ionic liquids as their suppressors in liquid chromatography.

In this review, we will firstly discuss the types and the general properties of silica, focusing on the silica support used in chromatography and capillary electrophoresis. Additionally, the characterization of functional groups (silanols and siloxanes) will be considered in terms of activity of the stationary phases. We will then discuss physical chemistry of the stationary phases applied in liquid chromatography and capillary electrophoresis.

How to model temporal changes in nontargeted metabolomics study? A Bayesian multilevel perspective.

Analysis of time series data addresses the question on mechanisms underlying normal physiology and its alteration under pathological conditions. However, adding time variable to high-dimension, collinear, noisy data is a challenge in terms of mining and analysis. Here, we used Bayesian multilevel modeling for time series metabolomics in vivo study to model different levels of random effects occurring as a consequence of hierarchical data structure.

Untargeted Metabolomics Provides Insight into the Mechanisms Underlying Resistant Hypertension.

Background: Resistant hypertension (RH) affects about 15-20% of treated hypertensive patients worldwide. RH increases the risk of cardiovascular events such as myocardial infarction and stroke by 50%. The pathological mechanisms underlying resistance to treatment are still poorly understood.

Metabolomic Heterogeneity of Urogenital Tract Cancers Analyzed by Complementary Chromatographic Techniques Coupled with Mass Spectrometry.

Background: In regard to urogenital tract cancer studies, an estimated 340,650 new cases and 58,360 deaths from genital system cancer and about 141,140 new cases and 29330 deaths from urinary system were projected to occur in the United States in 2012. The main drawbacks of currently available diagnostic tests constitute the low specificity, costliness and quite high invasiveness.

Objective: The main goal of this pilot study was to determine and compare urine metabolic fingerprints in urogenital tract cancer patients and healthy controls.

Quantitative determination of trigonelline in mouse serum by means of hydrophilic interaction liquid chromatography-MS/MS analysis: Application to a pharmacokinetic study.

Trigonelline is a pyridine alkaloid found in fenugreek seeds and coffee beans. Most of the previous studies are concerned with the quantification of trigonelline along with other constituents in coffee herbs or beverages. Only a few have focused on its determination in animal or human tissues by applying different modes of HPLC with UV or MS detection.

pH-Gradient Liquid Chromatography: Fundamentals and Examples.

In this paper, we acquaint the readers with the fundamentals of gradient separation, followed by the latest innovations in this field. We describe the principles of organic modifier- and pH-gradient elution emphasizing the differences and similarities with isocratic separation. The double organic modifier-/pH-gradient is also thoroughly reviewed as a useful method for the simultaneous determination of logkw (substitute of logP) and the pka of analytes present in complex mixtures.

Are Alpha-2D Adrenoceptor Subtypes Involved in Rat Mydriasis Evoked by New Imidazoline Derivatives: Marsanidine and 7-Methylmarsanidine?

The imidazoline compounds may produce mydriasis after systemic administration to some species (rats, cats, and mice). In mydriatic activity of imidazolines, α-adrenoceptors subtype(s) seems to be involved. In this study, the pupil dilatory effect evoked by 2 newly synthesized imidazoline derivatives-α-adrenoceptor agonists: marsanidine and 7-methylmarsanidine-was compared.

Comparative pharmacodynamic analysis of imidazoline compounds using rat model of ocular mydriasis with a test of quantitative structure-activity relationships.

Imidazol(in)e derivatives, having the chemical structure similar to clonidine, exert diverse pharmacological activities connected with their interactions with alpha2-adrenergic receptors, e.g. hypotension, bradycardia, sedation as well as antinociceptive, anxiolytic, antiarrhythmic, muscle relaxant and mydriatic effects.

Multilevel pharmacokinetics-driven modeling of metabolomics data.

Introduction: Multilevel modeling is a quantitative statistical method to investigate variability and relationships between variables of interest, taking into account population structure and dependencies. It can be used for prediction, data reduction and causal inference from experiments and observational studies allowing for more efficient elucidation of knowledge.

Objectives: In this study we introduced the concept of multilevel pharmacokinetics (PK)-driven modelling for large-sample, unbalanced and unadjusted metabolomics data comprising nucleoside and creatinine concentration measurements in urine of healthy and cancer patients.

Evaluation of in silico pharmacokinetic properties and in vitro cytotoxic activity of selected newly synthesized N-succinimide derivatives.

Design of a new drug entity is usually preceded by analysis of quantitative structure activity (properties) relationships, QSA(P)R. Six newly synthesized succinimide derivatives have been determined for (i) in silico physico-chemical descriptors, pharmacokinetic and toxicity predictors, (ii) in vitro biological activity on four different carcinoma cell lines and on normal fetal lung cells and (iii) lipophilicity on liquid chromatography. All compounds observed were predicted for good permeability and solubility, good oral absorption rate and moderate volume of distribution as well as for modest blood brain permeation, followed by acceptable observed toxicity.

HPLC-MS/MS method for dexmedetomidine quantification with Design of Experiments approach: application to pediatric pharmacokinetic study.

Aim: The purpose of this work was to develop and validate a rapid and robust LC-MS/MS method for the determination of dexmedetomidine (DEX) in plasma, suitable for analysis of a large number of samples.

Method: Systematic approach, Design of Experiments, was applied to optimize ESI source parameters and to evaluate method robustness, therefore, a rapid, stable and cost-effective assay was developed. The method was validated according to US FDA guidelines.

An Approach Based on HPLC-Fingerprint and Chemometrics to Quality Consistency Evaluation of L. Commercial Samples.

Chamomile has been used as an herbal medication since ancient times and is still popular because it contains various bioactive phytochemicals that could provide therapeutic effects. In this study, a simple and reliable HPLC method was developed to evaluate the quality consistency of nineteen chamomile samples through establishing a chromatographic fingerprint, quantification of phenolic compounds and determination of antioxidant activity. For fingerprint analysis, 12 peaks were selected as the common peaks to evaluate the similarities of commercial samples of chamomile obtained from different manufacturers.

Robust HPLC-MS/MS method for levofloxacin and ciprofloxacin determination in human prostate tissue.

Fluoroquinolones are the drugs of choice in the prevention of bacterial infections after transrectal ultrasound guided prostate biopsy. In order to improve assessment of antibacterial efficacy in the target tissue a simple, selective, rapid and robust HPLC-ESI-MS/MS method for the determination of levofloxacin and ciprofloxacin concentrations in human prostate bioptates was developed and validated. Preparation procedure for prostate samples (10mg) was carried out using homogenization and filtration steps.