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PubMed1995

Interactions of Solutol HS 15 and Cremophor EL with plasma lipoproteins.

Two emulsifying agents, Solutol HS15 and Cremophor EL, were compared with regard to their effects on human plasma lipoproteins in vitro and on mouse plasma lipoproteins in vitro and in vivo. Both agents promoted binding of a hydrophobic photosensitizing agent (C8KC) to a circulating plasma species of low bouyant density. Persistence of this material was greater with Cremophor than with Solutol. Experiments carried out with labeled Solutol indicated that the vehicle itself is a component of this new species. High concentrations of either vehicle ( > or = 0.06%) led to decreased electrophoretic mobility of human LDL and HDL in vitro. In the mouse, a different effect was observed, resulting in complex changes in electrophoretic mobility of plasma lipoproteins. The plasma half-life of C8KC in the circulation of the mouse was correlated with the persistence of an altered electrophoretic lipoprotein pattern. Since Solutol and C8KC showed similar half-lives, this result suggests that the plasma half-life of the sensitizer is correlated with the persistence of the vehicle. While Solutol and Cremophor were designed to be vehicles for drug formulation, they also influence persistence of some drugs in the circulation.

Animals↗
PubMed1998

Application of an automated HS-GC method in partition coefficient determination for xylenes and ethylbenzene in rat tissues.

An automated static head space-gas chromatography method was used in the determination of partition coefficients (Kd) for the xylene isomers and ethylbenzene in blood, brain, muscle, kidney, liver and fat of Sprague Dawley rats. Since homogenization resulted in the potential loss of analytes from tissue samples, unhomogenized samples were used. With a few exceptions, tissue:air Kd values were independent of the concentrations of the analytes, singly or as a mixture. The tissue:blood Kd values were determined. For each tissue and analyte, the value obtained for each analyte concentration was within +/- 10% of the mean value calculated for the entire concentration range.

Animals↗
PubMed1998

Residual solvents determination in pharmaceutical products by GC-HS and GC-MS-SPME.

Solid-phase microextraction (SPME) has been applied to the residual solvents determination in pharmaceutical products and was compared with the static headspace. Three fibers with different polymer films were compared and the polydimethylsiloxane/divinylbenzene coated fiber was found to be the most sensitive for the analyzed analytes. Between the investigated sample preparation techniques, gastight-SPME proved to be the most sensitive, with DL values ranging from 5 pg ml(-1) to 2 ng ml(-1). Headspace SPME is more precise, with RSD of peak areas values ranging from 2 to 3%. The headspace SPME method was successfully validated. The validation data are reported in the text. The most important difference between the two techniques is that the gastight SPME showed better behavior towards very volatile solvents. Compared with the static headspace technique, both SPME methods showed superior results, being compatible with the pharmaceutical samples.

Drug Contamination↗
PubMed2003

Reductive desulfurization of allylic thiols by HS-/H2S in water gives clue to chemical reactions widespread in natural environments.

The reduction of allylic thiols to alkenes by hydrogen sulfide in aqueous solutions, a novel reaction that may explain reduction processes widely occurring in natural environments, has been discovered. Its mechanism has been studied and suggested to follow an S(RN)1-like pathway involving radical intermediates undergoing 1,4 hydrogen shifts. [reaction: see text]

Alkenes↗
PubMed2003

Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo.

We have previously shown that thalidomide and its potent immunomodulatory derivatives (IMiDs) inhibit the in vitro growth of multiple myeloma (MM) cell lines and patient MM cells that are resistant to conventional therapy. In this study, we further characterize the effect of these drugs on growth of B cell malignancies and angiogenesis. We established a beige-nude-xid (BNX) mouse model to allow for simultaneous in vivo measurement of both anti-tumor and anti-angiogenic effects of thalidomide and its analogs. Daily treatment (50 mg/kg/d) with thalidomide or IMiDs was nontoxic. The IMiDs were significantly more potent than thalidomide in vivo in suppressing tumor growth, evidenced by decreased tumor volume and prolonged survival, as well as mediating anti-angiogenic effects, as determined by decreased microvessel density. Our results therefore show that the IMiDs have more potent direct anti-tumor and anti-angiogenic effects than thalidomide in vivo, providing the framework for clinical protocols evaluating these agents in MM and other B cell neoplasms.

Angiogenesis Inhibitors↗