Simultaneous Rp-Hplc Method For Determination Of Betamethasone Dipropionate And Tolnaftate In Combined Semisolid Formulation

A new RP-HPLC method was developed for selective and simultaneous determination of betamethasone dipropionate and tolnaftate in combined semisolid formulation containing other components. Further, the proposed method was validated for linearity, precision (system precision, method precision, intermediate or inter-day precision), accuracy, stability in analytical solution, robustness or system suitability and ruggedness. The developed method exhibited the best results in terms of the aforesaid validation parameters. The other components and additives did not interfere in their determinations. The method was found to be selective, simple, economical, accurate, reproducible, rapid and reliable for routine estimation purpose of these drugs in combined semisolid formulations.

Development and Validation of Head-space Gas Chromatographic Method in Tandem with Flame ionized detection for the determination of Residual solvents in Simeprevir API Synthesis

Residual solvent testing is an integral part of reference material certification. A gas chromatography/flame ionization detector/headspace method has been developed and validated to detect and quantitate commonly used residual solvents in our production processes: Methanol, Tetrahydrofuran, Toluene, Dichloromethane and Dichloroethane in Simeprevir API. A simple and selective HS-GC method is described for the determination & quantification of Residual Solvents in Simeprevir API. Chromatographic separation was achieved on USP G43 equivalent capillary column Thermo Scientific™ Trace GOLD™ TG-624 SilMS, 30m × 0.32mm × 1.8µm column (P/N 26059-3390) using nitrogen as carrier gas by using different temperature gradient of FID Detectors. Linearity was observed in the range 40-120% of standard concentrations for Methanol, Tetrahydrofuran, Toluene, Dichloromethane and Dichloroethane (r2>0.999) for the amount of solvent estimated by the proposed methods was in good agreement. The proposed methods were validated. The accuracy of the methods was assessed by recovery studies at three different levels. Recovery experiments indicated the absence of interference from commonly encountered diluent and API. The method was found to be precise as indicated by the repeatability analysis, showing %RSD less than 10 for Methanol, Tetrahydrofuran, Toluene, Dichloromethane and Dichloroethane. All statistical data proves validity of the methods and can be used for routine analysis of pharmaceutical active ingredients for estimation of Residual Solvents of Methanol, Tetrahydrofuran, Toluene, Dichloromethane and Dichloroethane in Simeprevir. Baseline separation of all five solvents and Simeprevir API is achieved within 20.5 minutes of analysis time. Method validation comprised the following parameters: limit of detection (LOD), limit of quantitation (LOQ), linearity and range, accuracy, precision (repeatability and intermediate precision), system suitability, specificity, and robustness. Linearity and LOQ (ppm) are listed for each solvent in manuscript. The present method was proven to be robust and accurate for quantitative analysis of residual solvent in neat materials.

Varicocele-Mediated Male Infertility: From the Perspective of Testicular Immunity and Inflammation

BackgroundVaricocele (VC) is present in 35 - 40% of men with infertility. However, current surgical and antioxidant treatments are not completely effective. In addition to oxidative stress, it is likely that other factors such as testicular immune microenvironment disorder contribute to irreversible testicular. Evidence suggests that VC is associated with anti-sperm antibodies (ASAs), spermatogenesis and testosterone secretion abnormalities, and testicular cytokine production. Moreover, inhibition of inflammation can alleviate VC-mediated pathogenesis. The normal function of the testis depends on its immune tolerance mechanism. Testicular immune regulation is complex, and many infectious or non-infectious diseases may damage this precision system.ResultsThe testicular immune microenvironment is composed of common immune cells and other cells involved in testicular immunity. The former includes testicular macrophages, T cells, dendritic cells (DCs), and mast cells, whereas the latter include Leydig cells and Sertoli cells (SCs). In animal models and in patients with VC, most studies have revealed an abnormal increase in the levels of ASAs and pro-inflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha in the seminal plasma, testicular tissue, and even peripheral blood. It is also involved in the activation of potential inflammatory pathways, such as the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing (NLRP)-3 pathway. Finally, the development of VC-mediated infertility (VMI) may be facilitated by abnormal permeability of proteins, such as claudin-11, that constitute the blood-testis barrier (BTB).ConclusionsThe testicular immune response, including the production of ASAs and inflammatory factors, activation of inflammatory pathways, and destruction of the BTB may be involved in the pathogenesis of VMI it is necessary to further explore how patient outcomes can be improved through immunotherapy.

HSE Consequences of FPSO Mooring Lines Pretension Uncertainty in Deep Waters Applications

The purpose of FPSO (Floating Production Storage and Offloading) mooring system is to keep the unit operating in site in order to attend the Health, Safety and Environment (HSE) requirements and to meet the production risers design requirements. The pretension specification is a design task and it is a key activity due to its influence on extreme loads and fatigue life for both the mooring lines and risers. It is surprising that the project pretension specifications are not always actually implemented in practice and followed during all the unit life. Some inaccurate methods are used to get the actual pretension and may cause significant errors, and this may cause pretensions values outside design allowable tolerances. A contemporary uncertainty analysis method that uses numerical simulations to estimate the consequences and propagation of the uncertainties in pretensions is applied. A case study is presented for the case of an operating FPSO moored by a spread system, offshore Brazil. A second investigation compares the uncertainty of pretensions measured by means of sensors with the uncertainties that arise from indirect measurements by top angles and as built data for mooring segments and anchor points. The paper finally shows the need of a Mooring Integrity Management (MIM) implementation of at least annual pretension measurements with a robust and higher precision system.

Comprehensive Temperature Control of a Hot Metal Rolling Thickness Measurement System

The work is devoted to the development of integrated thermostating subsystem of a high-precision system for measuring the thickness of hot metal rolling. The developed thermostatting subsystem includes active and passive modules, which ensured thermostability of the measuring modules at the level of 0.5 degrees in a hot metallurgical workshop. Thermal stabilization made it possible to ensure high accuracy in measuring the thickness of hot metal rolling in a hot metallurgical production workshop.

Determination of Possible Potential Genotoxic Impurities in Lenalidomide Drug Substance by Simple RP-HPLC Method

This study is concerned with development and validation of HPLC method for the simultaneous detection and quantification of methyl 2-(chloromethyl)-3-nitrobenzoate (MCN), methyl 2-(bromomethyl)-5-nitrobenzoate (MMM), methyl 2-(bromomethyl)-6-nitrobenzoate (MON), methyl 2-(bromomethyl)-4-nitrobenzoate (MPN) and 2-methyl-3-nitrobenzoic acid methyl ester (MNM), which are the genotoxic impurities of lenalidomide. Chromatographic separation was accomplished using a Waters HPLC system equipped with Ascentis Express F5 (150 × 4.6 mm, 2.7 μm) using mobile phase composed of solvent A (0.1% perchloric acid): solvent B (methanol 80% and acetonitrile 20%); 55:45, vol/vol. The selected impurities were detected using UV detector set at 210 nm. The standard curves showed linearity in the range of concentrations 4.59-91.2 ppm (for MCN), 6.58-90.0 ppm (for MMM), 3.96-89.1 ppm (for MON), 6.47-89.7 ppm (for MPN) and 4.28-90.1 ppm (for MNM). The statistical results of method precision, system precision, specificity, accuracy, ruggedness was found to be within limits of acceptance. All the impurities were stable in lenalidomide test samples up to 24 h.

DYNAMIC PROCESSES ANALYSIS IN THE TEMPERATURES STABILIZATION SYSTEM, IN THE INCUBATIOM CHAMBER

Thermal processes in incubation chamber were investigated. From the investigations, the recommendations were developed for controlling the temperature in this precision system based on the synthesis of correcting devices, allowing one to improve its functional quality.