Enantioselective analysis of unbound tramadol, O-desmethyltramadol and N-desmethyltramadol in plasma by ultrafiltration and LC-MS/MS: Application to clinical pharmacokinetics

This study describes the enantioselective analysis of unbound and total concentrations of tramadol and its main metabolites O-desmethyltramadol (M1) and N-desmethyltramadol (M2) in human plasma. Sample preparation was preceded by an ultrafiltration step to separate the unbound drug. Both the ultrafiltrate and plasma samples were submitted to liquid/liquid extraction with methyl t-butyl ether. Separation was performed on a Chiralpak (R) AD column and tandem mass spectrometry consisting of an electrospray ionization source, positive ion mode and multiple reaction monitoring was used as the detection system. Linearity was observed in the following ranges: 0.2-600 and 0.5-250 ng/mL for analysis of total and unbound concentrations of the tramadol enantiomers, respectively, and 0.1-300 and 0.25-125 ng/mL for total and unbound concentrations of the M1 and M2 enantiomers, respectively. The lower limits of quantitation were 0.2 and 0.5 ng/mL for analysis of total and unbound concentration of each tramadol enantiomer, respectively, and 0.1 and 0.25 ng/mL for total and unbound concentrations of M1 and M2 enantiomers, respectively. Intra- and interassay reproducibility and inaccuracy did not exceed 15%. Clinical application of the method to patients with neuropathic pain showed plasma accumulation of (+)-tramadol and (+)-M2 after a single oral dose of racemic tramadol. Fractions unbound of tramadol, M1 or M2 were not enantioselective in the patients investigated. (C) 2011 Elsevier B.V. All rights reserved.

The young stellar cluster [DBS2003] 157 associated with the H ii region GAL 331.31-00.34

We report a study of the stellar content of the near-infrared (NIR) cluster [DBS2003] 157 embedded in the extended H ii region GAL 331.31-00.34, which is associated with the IRAS source 16085-5138. JHK photometry was carried out in order to identify potential ionizing candidates, and the follow-up NIR spectroscopy allowed the spectral classification of some sources, including two O-type stars. A combination of NIR photometry and spectroscopy data was used to obtain the distance of these two stars, with the method of spectroscopic parallax: IRS 298 (O6 V, 3.35 +/- 0.61 kpc) and IRS 339 (O9 V, 3.24 +/- 0.56 kpc). Adopting the average distance of 3.29 +/- 0.58 kpc and comparing the Lyman continuum luminosity of these stars with that required to account for the radio continuum flux of the H ii region, we conclude that these two stars are the ionizing sources of GAL 331.31-00.34. Young stellar objects (YSOs) were searched by using our NIR photometry and mid-infrared (MIR) data from the Galactic Legacy Infrared Mid-Plane Survey Extraordinaire (GLIMPSE) survey. The analysis of NIR and MIR colourcolour diagrams resulted in 47 YSO candidates. The GLIMPSE counterpart of IRAS 16085-5138, which presents IRAS colour indices compatible with an ultracompact H ii region, has been identified. The analysis of its spectral energy distribution between 2 and m revealed that this source shows a spectral index a= 3.6 between 2 and m, which is typical of a YSO immersed in a protostellar envelope. Lower limits to the bolometric luminosity and the mass of the embedded protostar have been estimated as L= 7.7 x 10(3) L? and M= 10 M?, respectively, which correspond to a B0B1 V zero-age main sequence star.

Cadmium Uptake by Lettuce (Lactuca sativa L.) as Basis for Derivation of Risk Limits in Soils

The availability and uptake of Cd by lettuce (Lactuca sativa L.) in two common tropical soils (before and after liming) were studied in order to derive human health-based risk soil concentration. Cadmium concentrations ranging from 1 to 12 mg kg(-1) were added to samples from a clayey Oxisol and a sandy-loam Ultisol under glasshouse conditions. After incubation, a soil sample was taken from each pot, the concentration of Cd in the soil was determined, lettuce was grown during 36 d, and the edible parts were harvested and analyzed for Cd. A positive linear correlation was observed between total soil Cd and the Cd concentration in lettuce. The amount of Cd absorbed by lettuce grown in the Ultisol was about twice the amount absorbed in the Oxisol. Liming increased the soil pH and slightly reduced Cd availability and uptake. CaCl2 extraction was better than DTPA to reflect differences in binding strength of Cd between limed and unlimed soils. Risk Cd concentrations in the Ultisol were lower than in the Oxisol, reflecting the greater degree of uptake from the Ultisol. The derived risk Cd values were dependent on soil type and the exposure scenario.