HPLC-ESI-MS method development for the elucidation of nicardipine degradation products

Purpose: Nicardipine is a member of a family of calcium channel blockers named dihydropiridines that are known to be photolabile and may cause phototoxicity. It is therefore vital to develop analytical method which can study the photodegradation of nicardipine. Method: Forced acid degradation of nicardipine was conducted by heating 12 ml of 1 mg/ml nicardipine with 3 ml of 2.5 M HCl for two hours. A gradient HPLC medthod was developed using Agilent Technologies 1200 series quaternary system. Separation was achieved with a Hichrome (250 x 4.6 mm) 5 μm C18 reversed phase column and mobile phase composition of 70% A(100%v/v water) and 30% B(99%v/v acetonitrile + 1%v/v formic acid) at time zero, composition of A and B was then charged to 60%v/v A;40%v/v B at 10minutes, 50%v/v A; 50%v/v B at 30minutes and 70%v/v A; 30%v/v B at 35minutes. 20μl of 0.8mg/ml of nicardipine degradation was injected at room temperature (25oC). The gradient method was transferred onto a HPLC-ESI-MS system (HP 1050 series - AQUAMAX mass detector) and analysis conducted with an acid degradation concentration of 0.25mg/ml and 20μl injection volume. ESI spectra were acquired in positive ionisation mode with MRM 0-600 m/z. Results: Eleven nicardipine degradation products were detected in the HPLC analysis and the resolution (RS) between the respective degradants where 1.0, 1.2, 6.0, 0.4, 1.7, 3.7, 1.8, 1.0, and 1.7 respectively. Nine degradation products were identified in the ESI spectra with the respective m/z ratio; 171.0, 166.1, 441.2, 423.2, 455.2, 455.2, 331.1, 273.1, and 290.1. The possible molecular formulae for each degradants were ambiguously determined. Conclusion: A sensitive and specific method was developed for the analysis of nicardipine degradants. Method enables detection and quantification of nicardipine degradation products that can be used for the study of the kinetics of nicardipine degradation processes.

Predictions of segregation of granular material with the aid of PHYSICA, a 3-D unstructured finite-volume modelling framework

In this paper a continuum model for the prediction of segregation in granular material is presented. The numerical framework, a 3-D, unstructured grid, finite-volume code is described, and the micro-physical parametrizations, which are used to describe the processes and interactions at the microscopic level that lead to segregation, are analysed. Numerical simulations and comparisons with experimental data are then presented and conclusions are drawn on the capability of the model to accurately simulate the behaviour of granular matter during flow.

A coarse grid extraction of sound signals for computational aeroacoustics

Sound waves are propagating pressure fluctuations, which are typically several orders of magnitude smaller than the pressure variations in the flow field that account for flow acceleration. On the other hand, these fluctuations travel at the speed of sound in the medium, not as a transported fluid quantity. Due to the above two properties, the Reynolds averaged Navier–Stokes equations do not resolve the acoustic fluctuations. This paper discusses a defect correction method for this type of multi-scale problems in aeroacoustics. Numerical examples in one dimensional and two dimensional are used to illustrate the concept. Copyright (C) 2002 John Wiley & Sons, Ltd.

Parallel CFD fire modelling on office PCs with dynamic load balancing

Parallel processing techniques have been used in the past to provide high performance computing resources for activities such as Computational Fluid Dynamics. This is normally achieved using specialized hardware and software, the expense of which would be difficult to justify for many fire engineering practices. In this paper, we demonstrate how typical office-based PCs attached to a local area network have the potential to offer the benefits of parallel processing with minimal costs associated with the purchase of additional hardware or software. A dynamic load balancing scheme was devised to allow the effective use of the software on heterogeneous PC networks. This scheme ensured that the impact between the parallel processing task and other computer users on the network was minimized thus allowing practical parallel processing within a conventional office environment. Copyright © 2006 John Wiley & Sons, Ltd.

Numerical algorithms for modelling electrodeposition: Tracking the deposition front under forced convection from megasonic agitation

Electrodeposition is a widely used technique for the fabrication of high aspect ratio microstructures. In recent years, much research has been focused within this area aiming to understand the physics behind the filling of high aspect ratio vias and trenches on substrates and in particular how they can be made without the formation of voids in the deposited material. This paper reports on the fundamental work towards the advancement of numerical algorithms that can predict the electrodeposition process in micron scaled features. Two different numerical approaches have been developed, which capture the motion of the deposition interface and 2-D simulations are presented for both methods under two deposition regimes: those where surface kinetics is governed by Ohm’s law and the Butler–Volmer equation, respectively. In the last part of this paper the modelling of acoustic forces and their subsequent impact on the deposition profile through convection is examined.

Practical solvent system selection for counter-current separation of pharmaceutical compounds

Counter-current chromatography (CCC) is a technique that shows a lot of potential for large scale purification. Its usefulness in a "research and development" pharmaceutical environment has been investigated, and the conclusions are shown in this article. The use of CCC requires the development of an appropriate solvent system (a parameter of critical importance), a process which can be tedious. This article presents a novel strategy, combining a statistical approach and fast HPLC to generate a three-dimensional partition coefficient map and rapidly predict an optimal solvent system. This screen is performed in half a day and involves 9 experiments per solvent mixture. Test separations were performed using that screen to ensure the validity of the method.

Triterpenoid saponins from the cytotoxic root extract of Sideroxylon foetidissimum, an endemic Yucatecan medicinal plant

The flora of the Yucatan peninsula (Mexico) includes approximately 3000 plant species. Sideroxylon foetidissimum Jacq. subsp. gaumeri (Sapotaceae) is an endemic plant to the Yucatan peninsula; its fruit is edible and local people use the plant for medicinal purposes, although no details on its preparation or application are available [1,2]. A preliminary cytotoxic evaluation of the ethanolic root extract of S. foetidissimum revealed a potent activity against murine macrophage like cell line RAW 264.7 (IC50=39.54±4.11µg/mL). The systematic bioassay-guided fractionation of the extract resulted in the identification of the active saponin-containing fraction (IC50=33.69±6.19µg/mL). Four new triterpenoid saponins and a 1:1 mixture of two saponins were isolated from the active saponin- containing fraction. The evaluation of their cytotoxic activity revealed no activity for the tested pure saponins; however, the 1:1 mixture of saponins showed a potent activity (IC50=11.91±1.49µg/mL). The isolation of the saponins was carried out using semi-preparative HPLC. The structural assignments of the pure saponins were based on 1D (1H and 13C and DEPT-135) and 2D (COSY, HMBC, HSQC and TOCSY) NMR and mass spectrometry analyses. In this presentation, the isolation, identification and cytotoxic activity of the isolated compounds is discussed in more detail.