This paper describes the evaluation of a system for computer-controlled discrete sampling and stopped-flow mixing for equilibrium and kinetic determinations of several sorts of analytes in human serum. The instrumental system features a wash-out sampling system that permits rapid change-over from one sample and (or) reagent type to another, and a mixing/measurement system that can provide reliable data as soon as 10 ms after reagent and sample are mixed. Examples discussed include equilibrium procedures for glucose and cholesterol, slow kinetic procedures for glucose and lactate dehydrogenase, and a fast kinetic method for thiocyanate. The regression equation for all stopped-flow results (n = 114) vs. results by conventional methods is y = (1.03 ± 0.01)x(0.016 ± 0.0 19) for numerical values of ybetween 0.3 and 3.0. The correlation coefficient for these data was 0.991. These results demonstrate that the stopped-flow method is a viable analytical approach for equilibrium, slow kinetic, and fast kinetic determinations that require measurement times shorter than 0.1 s.

Potent and selective inhibition of matrix metalloproteinases was demonstrated for a series of sulfonamide-based hydroxamic acids. The design of the heterocyclic sulfonamides incorporates a six- or seven-member central ring with a P2' substituent that can be modified. Binding interactions of this substituent at the S2' site are believed to contribute to high inhibitory potency against stromelysin, collagenase-3 and gelatinases A and B, and to provide selectivity against collagenase-1 and matrilysin. An X-ray structure of a stromelysin inhibitor complex was obtained to provide insights into the SAR and selectivity trends observed for the series.

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We have adapted for glucose determination a new ap- proach to kinetic analyses (Anal. Chem. 50, 1611(1978)); it is 50-fold less dependent upon some experimental variables than is a more conventional rate method. Modi- fication of a commercially available hexokinase/glu- cose-6-phosphate dehydrogenase reagent system for glucose provides that the rate of production of NADH be first-order in-total glucose concentration within about 30 s after sample and reagent are mixed. In the kinetic method, absorbance vs. time data recorded after 30 s and a multiple-linear-regression program are used to compute the absorbance change that would occur if the reaction were monitored to completion. Results demonstrate a linear relationship between glucose concentration and computed absorbance change. Application of the method to 51 human sera without rigorous control of either tem- perature or reagent composition yielded a regression equation of y = 1.Olx- 0.3 when kinetic results (y) were compared with equilibrium results (x) for the same samples analyzed in a hospital laboratory. We report the establishment of conditions by which the hexokinase/glucose-6-phosphate dehydrogenase coupled- reaction system can be used for the kinetic determination of total glucose, and the adaptation of this reaction system to a new approach for kinetic analyses (1) in which dependencies upon experimental variables are much closer to equilibrium methods than to the more common kinetic methods. The re- action system becomes first-order in total glucose (a- and f3-D-glucose) in less than 30 s after sample and reagent are