Micromachining technology was used to prepare chemical analysis systems on glass chips (1 centimeter by 2 centimeters or larger) that utilize electroosmotic pumping to drive fluid flow and electrophoretic separation to distinguish sample components. Capillaries 1 to 10 centimeters long etched in the glass (cross section, 10 micrometers by 30 micrometers) allow for capillary electrophoresis-based separations of amino acids with up to 75,000 theoretical plates in about 15 seconds, and separations of about 600 plates can be effected within 4 seconds. Sample treatment steps within a manifold of intersecting capillaries were demonstrated for a simple sample dilution process. Manipulation of the applied voltages controlled the directions of fluid flow within the manifold. The principles demonstrated in this study can be used to develop a miniaturized system for sample handling and separation with no moving parts.

Micromachining a miniaturized capillary electrophoresis-based chemical analysis system on a chip

The Golden Age of Transfer Hydrogenation

Matrix effects: the Achilles heel of quantitative high-performance liquid chromatography-electrospray-tandem mass spectrometry.

Separation of enantiomers: needs, challenges, perspectives☆

Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, typically only a fraction of these have sufficient ADME/Tox properties to become a drug product. Understanding ADME/Tox is critical for all drug researchers, owing to its increasing importance in advancing high quality candidates to clinical studies and the processes of drug discovery. If the properties are weak, the candidate will have a high risk of failure or be less desirable as a drug product. This book is a tool and resource for scientists engaged in, or preparing for, the selection and optimization process. The authors describe how properties affect in vivo pharmacological activity and impact in vitro assays. Individual drug-like properties are discussed from a practical point of view, such as solubility, permeability and metabolic stability, with regard to fundamental understanding, applications of property data in drug discovery and examples of structural modifications that have achieved improved property performance. The authors also review various methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties. * Serves as an essential working handbook aimed at scientists and students in medicinal chemistry * Provides practical, step-by-step guidance on property fundamentals, effects, structure-property relationships, and structure modification strategies * Discusses improvements in pharmacokinetics from a practical chemist's standpoint

Drug-Like Properties: Concepts, Structure Design and Methods from ADME to Toxicity Optimization

In recent years there has been considerable interest in the characterization of experimental chromatographic peaks. Presented in Table I are the names, symbols, and general expressions that have evolved for the parameters used in chromatographic peak characterization. It is proposed that these parameters be referred to collectively

Equations for calculation of chromatographic figures of merit for ideal and skewed peaks

In “comprehensive” two-dimensional liquid chromatography, the column effluent from the first separation system (the first dimension) is sequentially sampled by the second dimension separation system. The total analysis time is largely determined by the speed of the second dimension separation system; the most retained component must elute before the least retained component of the next second dimension separation. Optimization of multidimensional separation systems requires that one understand the relationship between system resolution and the number of second dimension samples across a first dimension peak. In this paper, we study the theoretical and experimental aspects of this sampling process. To obtain high two-dimensional resolution, each peak in the first dimension should be sampled at least three times into the second dimension when the sampling is in-phase. If the sampling is maximally out of phase, there should be at least four samples per peak for high-fidelity separation. The sensitivity of th...

Effect of Sampling Rate on Resolution in Comprehensive Two-Dimensional Liquid Chromatography

A Review of the Exponentially Modified Gaussian (EMG) Function: Evaluation and Subsequent Calculation of Universal Data

Current problems with the limit of detection (LOD) concept in chromatography are reviewed. They include the confusion of the LOD with other separate, distinct concepts in trace analysis such as the minimum detectability (MD); the use of arbitrary, unjustified models for the calculation of the LOD; the use of concentration units instead of units of amount; and the failure to account for differences in chromatographic conditions when comparing LODS. Solutions to these LOD problems are discussed. Two models are proposed for calculating the chromatographic LOD. A new concept, the standardized chromatographic LOD, is introduced to account for differences in chromatographic bandwidths of experimentally measured LODs. The standardized chromatographic LOD is shown to be a more reliable parameter than the conventional (non-standardized) chromatographic LOD.

Clarification of the limit of detection in chromatography

surfactant concentratlon to use. Another equatlon Is dedved that relates the analysts time to flve parameters: R,, a (rdectlvlty), & r, fJfm, and H/v, (plate helght/electroo#notlc vdoclty). The capacity factor for the best tusddbn k glven by k = (fJfo)1'2, where 1, and I, are the retentbn times of the aqueous and mlceHar phases, respectively. The capadty factor for the best regolMkn per unH the rangw from 1.2 to 2. The separatbns obtained by -the optknun capedty factor for rm per unit tkne Instead of re8olutlon may be Owsmy poorer In terms of resolutlon but are much faster. Provided the opthnum condltkns are employed, the qusyty of MEC separatkns Is Independent of the solute hydraphoblcity. The advantages of a surfactant gradient for the separation of solutes with a wlde range of hydrare dkussed. A brW comparlsan of MEC, mlcellar liquid chromatography, and conventional hlgh-performance llquld chromatography is also made.

Joe P. Foley

Papers

Equations for calculation of chromatographic figures of merit for ideal and skewed peaks

Effect of Sampling Rate on Resolution in Comprehensive Two-Dimensional Liquid Chromatography

A Review of the Exponentially Modified Gaussian (EMG) Function: Evaluation and Subsequent Calculation of Universal Data

Clarification of the limit of detection in chromatography

Optimization of Micellar Electrokinetic Chromatography