16) The data in Table I show the fraction of the barrier that is eliminated after partial distortion of CBD from the rectangular minimum toward a square geometry. (17) Maier, G.; Schafer, U.; Sauer, W.; Hartan, H.; Oth, J. F. M. Tetrahedron Lett. 1978, 1837. This explanation has been suggested by Bally, T.;Masamune, S. Tetrahedron 1980,36,343. An alternative explanation is that C-1 and C-3, which are nonequivalent in a rectangular geometry, nevertheless, have nearly identical chemical shifts.(18) It should be noted that the geometry and apparent diamagnetic nature of 3 provide evidence for the correctness of the theoretical prediction of a singlet ground state for CBD, even at a square g e~m e t r y .~~~'~~~'~ (19) Buenker, R. J.; Peyerimhoff, S. D.

Solid state amide hydrogen/deuterium exchange with mass spectrometric analysis (ssHDX-MS) was used to assess the conformation of myoglobin (Mb) in lyophilized formulations, and the results correlated with the extent of aggregation during storage. Mb was colyophilized with sucrose (1:1 or 1:8 w/w), mannitol (1:1 w/w), or NaCl (1:1 w/w) or in the absence of excipients. Immediately after lyophilization, samples of each formulation were analyzed by ssHDX-MS and Fourier transform infrared spectroscopy (FTIR) to assess Mb conformation, and by dynamic light scattering (DLS) and size exclusion chromatography (SEC) to determine the extent of aggregation. The remaining samples were then placed on stability at 25 °C and 60% RH or 40 °C and 75% RH for up to 1 year, withdrawn at intervals, and analyzed for aggregate content by SEC and DLS. In ssHDX-MS of samples immediately after lyophilization (t = 0), Mb was less deuterated in solids containing sucrose (1:1 and 1:8 w/w) than in those containing mannitol (1:1 w/w), NaCl (1:1 w/w), or Mb alone. Deuterium uptake kinetics and peptide mass envelopes also indicated greater Mb structural perturbation in mannitol, NaCl, or Mb-alone samples at t = 0. The extent of deuterium incorporation and kinetic parameters related to rapidly and slowly exchanging amide pools (Nfast, Nslow), measured at t = 0, were highly correlated with the extent of aggregation on storage as measured by SEC. In contrast, the extent of aggregation was weakly correlated with FTIR band intensity and peak position measured at t = 0. The results support the use of ssHDX-MS as a formulation screening tool in developing lyophilized protein drug products.

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We have developed a new system for clinical chemistry analysis, the Vision System, in which centrifugal force is used to separate whole blood, measure reagent and plasma volumes, and complete all steps required for a spectrophotometric analysis. The system is based on use of a multichambered plastic test pack containing liquid reagents, which can be centrifuged at 500 X g in two planes, oriented at right angles to each other. Alternating centrifugal fields allows liquid reagents and plasma to flow into highly precise measuring and mixing chambers. A unique flash lamp and diode array spectrometer provide for optical measurements of 10 test packs at as many as eight wavelengths simultaneously. The temperature of each individual test pack is controlled by using a flash lamp coupled to a liquid crystal temperature sensor. Microprocessor control allows as many as 10 different chemistry reactions to be measured simultaneously on whole-blood, plasma, or serum samples. Comparison with results by an established batch-photometric analyzer demonstrated excellent precision and accuracy for various clinical chemistry tests.

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