Analysis of the adult human plasma metabolome.

Objective: It is well established that disease states are associated with biochemical changes (e.g., diabetes/glucose, cardiovascular disease/cholesterol), as are responses to chemical agents (e.

High-throughput preparative process utilizing three complementary chromatographic purification technologies.

A high-throughput process was developed in which wells in plates generated from parallel synthesis are automatically channeled to an appropriate purification technique using analytical data as a guide. Samples are directed to either of three fundamentally different preparative techniques: HPLC with UV-triggered fraction collection, supercritical fluid chromatography (SFC) with UV-triggered fraction collection, or HPLC with MS-triggered fraction collection. Automated analysis of the analytical data identifies the product compound mass and creates work lists based on chromatographic properties exhibited in the data so that each preparative instrument cherry picks the appropriate list of samples to purify when a preparative-scale plate is loaded.

High-throughput bioassay-guided fractionation: a technique for rapidly assigning observed activity to individual components of combinatorial libraries, screened in HTS bioassays.

In this paper, we describe an automated, high-throughput analytical tool for the unambiguous characterization of the active component(s) of a combinatorially derived reaction mixture. We call this technique high-throughput bioassay-guided fractionation (BGF). The novel aspects of this communication are the systematization of the BGF concept, the application of BGF to combinatorial chemistry, and the high-throughput nature of the identification technique.

Effect of testosterone suppression on the pharmacokinetics of a potent gnRH receptor antagonist.

Purpose: The expression of cytochrome P450 enzymes (CYPs) in animals and humans is under complex hormonal regulation. Chronic treatment with drugs that alter sex hormone levels such as GnRH receptor agonists or antagonists may affect the expression of hormone-dependent CYPs, and as a result the pharmacokinetics of drugs metabolized by them.

Methods: Enzyme kinetic parameters were obtained by incubating AG-045572 (0.

Quantitative detection of eight phthalate metabolites in human urine using HPLC-APCI-MS/MS.

Because of the ubiquity of phthalates and their potential role in increasing risk for cancer and reproductive dysfunction, the need for human exposure assessment studies is urgent. In response to this need, we developed a high-throughput, robust, sensitive, accurate, and precise assay for simultaneous measurement of trace levels of eight phthalate metabolites in human urine by HPLC-MS/MS. Human urine samples were processed using enzymatic deconjugation of the glucuronides followed by solid-phase extraction.