Intercompany Study to Evaluate the Robustness of Capillary Isoelectric Focusing Technology for the Analysis of Monoclonal Antibodies

Interlaboratory comparisons are essential to bringing emerging technologies into biopharmaceutical industry practice and regulatory acceptance. As a result, an international team including 12 laboratories from 10 independent biopharmaceutical companies in the United States and Switzerland was formed to evaluate the precision and robustness of capillary isoelectric focusing (CIEF) to assess the charge heterogeneity of monoclonal antibodies. The different laboratories determined the apparent pI and the relative distribution of the charge isoforms of a representative monoclonal antibody (rMAb) sample using the same CIEF method. Statistical evaluation of the data was performed to determine within and between-laboratory consistencies and outlying information. The apparent pI data generated for each charge variant peak showed very good precision between laboratories with percentage of RSD values of ??0.5%. Similarly, the percentage of RSD for the rMAb charge variants percent peak area values are ??4.4% across different laboratories with different analysts using different lots of ampholytes and multiple instruments. Taken together, these results validate the appropriate use of CIEF in the biopharmaceutical industry in support of regulatory submissions.     

Modification of galvannealed steel through aluminum addition

Aluminum is believed to modify and to some extent control the coating characteristics of commercially produced galvanneal sheet steel. These include mechanical, chemical, and aesthetic properties. Whereas the aluminum added to the molten zinc bath is known to form intermetallics before the steel is annealed, our research is primarily concerned with the effect aluminum has on suppression or enhancement of the particular iron--zinc alloy phases in the coating during galvannealing. The microstructure of four commercially important iron--zinc intermetallic phases containing varying aluminum content between 0--1.5 weight percent has been studied. It is also believed that an iron--aluminum alloy, known as the inhibition layer, forms on the steel surface following hot dipping and prior to annealing. Transmission and scattering Mössbauer spectroscopy as well as X-ray diffraction have been used to identify iron--zinc and iron--aluminum alloys present in the coatings. Discussion will be presented on the effect aluminum has on phase suppression for Fe--Zn alloys prepared in commercially produced galvanneal.     

Use of xenon as a mobile phase for on–line capillary supercritical fluid chromatography–fourier transform infrared spectrometry

Xenon is investigated as a mobile phase for on-line capillary supercritical fluid chromatography-Fourier transform infrared spectrometry (SFC-FTIR). Polycyclic aromatic hydrocarbons, aromatic isocyanates, and epoxy acrylate oligomers are analyzed as examples to show that xenon has similar selectivities and solvating powe to CO₂. Its optical transparency makes it ideal for IR detection. A stop flow system is constructed to increase the sensitivity of spectra measured from compounds which are weak IR absorbers.     

Microwave-assisted, regioselective, Petasis olefination of unsymmetrical oxalates. Formation of pyruvate-based enol ethers and enamines

The Petasis olefination of unsymmetrical oxalates and oxalate monoesters/monoamides (tert-BuO₂CC(O)X, where X = OR, NR₂) is highly regioselective and provides pyruvate-based enol ether and enamine derivatives. The olefination step occurs under conventional thermal conditions, but is dramatically improved--shorter reaction times and higher yields--when promoted by microwave irradiation.     

The tautomerism of heteroaromatic compounds with 5-membered rings—XI 4-Hydroxyisoxazoles-4-isoxazolinones

Four 4-hydroxyisoxazoles together with model compounds have been investigated by UV, IR and NMR spectroscopy and by pK_a measurements, 4-Hydroxyisoxazoles exist predominantly in the hydroxy-form in a wide range of media.     

Fifth and sixth order PECE algorithms based on g-splines with improved stability characteristics

In this note fifth and sixth order PECE algorithms are presented. The corrector formulae are derived by using natural g-splines. The resulting PECE algorithms which use the Schoen predictor have larger regions of absolute stability and smaller truncation errors than the Krogh and Schoen algorithms of corresponding order.     

Optical-model analysis of 7Li + 25Mg and 7Li + 27Al elastic scattering at 89 MeV

The elastic scattering angular distributions for ⁷Li + ²⁵Mg and ⁷Li + ²⁷Al were measured at $\text{E(}{}^7\text{Li}\text{) = 89}\text{MeV}$ over angular ranges of 8–55° c.m. and 8–64° c.m. Previously published measurements for ^{24, 26}Mg at 89 MeV and ²⁴Mg at 34 MeV are reanalyzed. The cross sections were analysed using a 6-parameter phenomenological Saxon-Woods potential. No discrete ambiguities were found but the usual continuous ambiguities exist. The data were also analysed with double folded real potentials generated using the M3Y effective interaction. The folded potential must be multiplied by about 0.6 to fit the data. The extent to which ⁷Li optical-model potentials are determined and suggestions for further work on the normalization of the folded potential are discussed.