ALBERT

Description: A chromatographic method for the quantitation of promethazine (PMZ) and its three metabolites in urine employing on-line solid-phase extraction and column-switching has been developed. The column-switching system described here uses an extraction column for the purification of PMZ and its metabolites from a urine matrix. The extraneous matrix interference was removed by flushing the extraction column with a gradient elution. The analytes of interest were then eluted onto an analytical column for further chromatographic separation using a mobile phase of greater solvent strength. This method is specific and sensitive with a range of 3.75-1400 ng/ml for PMZ and 2.5-1400 ng/ml for the metabolites promethazine sulfoxide, monodesmethyl promethazine sulfoxide and monodesmethyl promethazine. The lower limits of quantitation (LLOQ) were 3.75 ng/ml with less than 6.2% C.V. for PMZ and 2.50 ng/ml with less than 11.5% C.V. for metabolites based on a signal-to-noise ratio of 10:1 or greater. The accuracy and precision were within +/- 11.8% in bias and not greater than 5.5% C.V. in intra- and inter-assay precision for PMZ and metabolites. Method robustness was investigated using a Plackett-Burman experimental design. The applicability of the analytical method for pharmacokinetic studies in humans is illustrated.

Description: The Indonesian Throughflow (ITF) spreading pathways and time scales in the Indian Ocean are investigated using both observational data and two numerical tracer experiments, one being a three-dimensional Lagrangian trajectory experiment and the other a transit-time probability density function (PDF) tracer experiment, in an ocean general circulation model. The model climatology is in agreement with observations and other model results except that speeds of boundary currents are lower. Upon reaching the western boundary within the South Equatorial Current (SEC), the trajectories of the ITF tracers within the thermocline exhibit bifurcation. The Lagrangian trajectory experiment shows that at the western boundary about 38%±5% thermocline ITF water flows southward to join the Agulhas Current, consequently exiting the Indian Ocean, and the rest, about 62%±5%, flows northward to the north of SEC. In boreal summer, ITF water penetrates into the Northern Hemisphere within the Somali Current. The primary spreading pathway of the thermocline ITF water north of SEC is upwelling to the surface layer with subsequent advection southward within the surface Ekman layer toward the southern Indian Ocean subtropics. There it is subducted and advected northward in the upper thermocline to rejoin the SEC. Both the observations and the trajectory experiment suggest that the upwelling occurs mainly along the coast of Somalia during boreal summer and in the open ocean within a cyclonic gyre in the Tropics south of the equator throughout the year. All the ITF water eventually exits the Indian Ocean along the western boundary within the Mozambique Channel and the east coast of Madagascar and, farther south, the Agulhas Current region. The advective spreading time scales, represented by the elapsed time corresponding to the maximum of transit- time PDF, show that in the upper thermocline the ITF crosses the Indian Ocean, from the Makassar Strait to the east coast of the African continent, on a time scale of about 10 yr and reaches the Arabian Sea on a time scale of over 20 yr.