The Degradation Chemistry of Prasugrel Hydrochloride: Part 1-Drug Substance.

Prasugrel hydrochloride is the active ingredient in Effient™, a thienopyridine platelet inhibitor. An extensive study of the degradation chemistry of prasugrel hydrochloride (LY640315 hydrochloride) has been carried out on the drug substance (part I) and on the drug product (part II, future article) using a multidimensional approach including hydrolytic, oxidative, and photolytic stressing, computational chemistry, HPLC analysis, and structure elucidation by various spectroscopic techniques. The major degradation products formed from the drug substance under the various stress conditions have been isolated and structures unambiguously determined, and the pathways leading to these products have been proposed.

Solution Stability of Poloxamer 188 Under Stress Conditions.

Poloxamer 188 (P188) is a triblock copolymer of the form polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO). The center PPO block is hydrophobic, and the side PEO blocks are hydrophilic, resulting in surface-active properties. P188 has been used in the pharmaceutical industry as an excipient in various formulations and drug delivery systems.

Chemical, experimental, and morphological evidence for diagenetically altered melanin in exceptionally preserved fossils.

In living organisms, color patterns, behavior, and ecology are closely linked. Thus, detection of fossil pigments may permit inferences about important aspects of ancient animal ecology and evolution. Melanin-bearing melanosomes were suggested to preserve as organic residues in exceptionally preserved fossils, retaining distinct morphology that is associated with aspects of original color patterns.

A 17-My-old whale constrains onset of uplift and climate change in east Africa.

Timing and magnitude of surface uplift are key to understanding the impact of crustal deformation and topographic growth on atmospheric circulation, environmental conditions, and surface processes. Uplift of the East African Plateau is linked to mantle processes, but paleoaltimetry data are too scarce to constrain plateau evolution and subsequent vertical motions associated with rifting. Here, we assess the paleotopographic implications of a beaked whale fossil (Ziphiidae) from the Turkana region of Kenya found 740 km inland from the present-day coastline of the Indian Ocean at an elevation of 620 m.

Novel lipoglycopeptides as inhibitors of bacterial signal peptidase I.

Signal peptidase (SPase) I is responsible for the cleavage of signal peptides of many secreted proteins in bacteria. Because of its unique physiological and biochemical properties, it serves as a potential target for development of novel antibacterial agents. In this study, we report the production, isolation, and structure determination of a family of structurally related novel lipoglycopeptides from a Streptomyces sp.