The Skaergaard trough layering: sedimentation in a convecting magma chamber.

The upper parts of the floor cumulates of the Skaergaard Intrusion, East Greenland, contain abundant features known as troughs. The troughs are gently plunging synformal structures comprising stacks of crescentic modally graded layers with a sharply defined mafic base that grades upward into plagioclase-rich material. The origin of the troughs and layering is contentious, attributed variously to deposition of mineral grains by magmatic currents descending from the nearby walls, or to in situ development by localised recrystallisation during gravitationally-driven compaction. They are characterised by outcrop-scale features such as mineral lineations parallel to the trough axis, evidence of erosion and layer truncation associated with migration of the trough axis, and disruption of layering by syn-magmatic slumping. A detailed microstructural study of the modal trough layers, using electron backscatter diffraction together with geochemical mapping, demonstrates that these rocks do not record evidence for deformation by either dislocation creep or dissolution-reprecipitation. Instead, the troughs are characterised by the alignment of euhedral plagioclase crystals with unmodified primary igneous compositional zoning. We argue that the lineations and foliations are, therefore, a consequence of grain alignment during magmatic flow. Post-accumulation amplification of the modal layering occurred as a result of differential migration of an unmixed immiscible interstitial liquid, with upwards migration of the Si-rich conjugate into the plagioclase-rich upper part of the layers, whereas the Fe-rich immiscible conjugate remained in the mafic base. Both field and microstructure evidence support the origin of the troughs as the sites of repeated deposition from crystal-rich currents descending from the nearby chamber walls.

Quality by Design: Multidimensional exploration of the design space in high performance liquid chromatography method development for better robustness before validation.

Robust HPLC separations lead to fewer analysis failures and better method transfer as well as providing an assurance of quality. This work presents the systematic development of an optimal, robust, fast UHPLC method for the simultaneous assay of two APIs of an eye drop sample and their impurities, in accordance with Quality by Design principles. Chromatography software is employed to effectively generate design spaces (Method Operable Design Regions), which are subsequently employed to determine the final method conditions and to evaluate robustness prior to validation.

Expanding the term "Design Space" in high performance liquid chromatography (I).

The current article presents a novel approach to applying Quality by Design (QbD) principles to the development of high pressure reversed phase liquid chromatography (HPLC) methods. Four common critical parameters in HPLC--gradient time, temperature, pH of the aqueous eluent, and stationary phase--are evaluated within the Quality by Design framework by the means of computer modeling software and a column database, to a satisfactory degree. This work proposes the establishment of two mutually complimentary Design Spaces to fully depict a chromatographic method; one Column Design Space (CDS) and one Eluent Design Space (EDS) to describe the influence of the stationary phase and of the mobile phase on the separation selectivity, respectively. The merge of both Design Spaces into one is founded on the continuous nature of the mobile phase influence on retention and the great variety of the stationary phases available.

Aspects of the "Design Space" in high pressure liquid chromatography method development.

The present paper describes a multifactorial optimization of 4 critical HPLC method parameters, i.e. gradient time (t(G)), temperature (T), pH and ternary composition (B(1):B(2)) based on 36 experiments. The effect of these experimental variables on critical resolution and selectivity was carried out in such a way as to systematically vary all four factors simultaneously. The basic element is a gradient time-temperature (t(G)-T) plane, which is repeated at three different pH's of the eluent A and at three different ternary compositions of eluent B between methanol and acetonitrile. The so-defined volume enables the investigation of the critical resolution for a part of the Design Space of a given sample. Further improvement of the analysis time, with conservation of the previously optimized selectivity, was possible by reducing the gradient time and increasing the flow rate. Multidimensional robust regions were successfully defined and graphically depicted.

The effect of age on the pharmacokinetics of levodopa administered alone and in the presence of carbidopa.

1. The effect of age on the pharmacokinetics of levodopa administered alone and in the presence of carbidopa was investigated in young and elderly healthy volunteers. 2. The plasma clearance of levodopa following intravenous administration of 50 mg was 14.2 +/- 2.8 (s.d.) ml min-1 kg-1 in the elderly compared with 23.4 +/- 4.1 ml min-1 kg-1 in the young (P less than 0.01) which resulted in a 49% greater area under the plasma concentration-time curve (AUC) in the older subjects (P less than 0.01). The volume of distribution (Vss) was lower in the elderly (1.01 +/- 0.29 l kg-1) than in the young (1.65 +/- 0.39 l kg-1) (P less than 0.002). 3. Following oral administration of 250 mg of levodopa the AUC was 2512 +/- 588 ng ml-1h in the elderly compared with 1056 +/- 282 ng ml-1h in the young (P less than 0.002). Cmax was also significantly greater in the elderly (P less than 0.05). The bioavailability of levodopa was significantly greater in the elderly (0.63 +/- 0.12 compared with 0.41 +/- 0.16, P less than 0.01). 4. In the presence of carbidopa, the plasma clearance of intravenous levodopa (50 mg) was reduced in both age groups but remained lower in the elderly (5.8 +/- 0.9 ml min-1 kg-1 compared with 9.3 +/- 1.0 ml min-1 kg-1; P less than 0.01). This resulted in a 54% greater AUC in the older subjects (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)