Robustness solution stability

Completion of tech transfei prior to product launch Specificity, linearity, range, accuracy, solution stability, precision, LOD, LOQ, robustness... 

Spray pyrolysis of ethanolic solutions of Fe(acetylacetone)3 or FeCls between 370°C and 450°C onto a glass substrate are reported for the fabrication of a-Fe20s thin-film photoanodes [75]. Upon illumination by a 150 W Xe lamp samples consistently demonstrate photocurrents of 0.9 mAcm , IPCE values up to 15%, and robust mechanical stability with no signs of photocorrosion for the undoped samples. With simultaneous multiple doping of 1% A1 and 5% Ti, an IPCE of 25% can be reached at 400 nm. Zn doping is known to induce p-type character in Ee20s thin film electrodes [76]. 

Robustness for HPLC Analysis. The investigation of the effect of column, mobile phase, HPLC solution stability, and wavelength is performed in a manner similar to the HPLC potency/related substance assay. For solution stability, the... 

Robustness for UV-Vis Analysis. Wavelength accuracy, wavelength repeatability, diluting solvent (i.e., pH, concentration), solution stability, and bubble formation by the sipper can be investigated during validation of the analytical component. 

Upon successful completion of the prevalidation audit, the analytical chemist simply performs the experiments listed in the validation protocol using the analytical method as written. Based on the results of the validation, it may be necessary to revise the method to include details such as solution stability, relative retention times, relative response factors, or cautionary statements resulting from the robustness experiments. 

Eurachem guide [285], which discusses when, why, and how methods should be validated. However, for the pharmaceutical industry, the main reference source is the ICH Guidelines [286], which provides recommendations on the various characteristics to be tested for the most common types of analytical procedures developed in a pharmaceutical laboratory. The main characteristics of any analytical method to be tested are specificity, linearity, accuracy, precision, solution stability, limits of detection and quantification, and robustness. Specific aspects should be considered for a CE method including method transfer between instrument manufacturers, reagent purity and source, electrolyte stability, capillary treatment and variations in new capillaries, and buffer depletion. Fabre and Altria [284] discuss CE method validation in more detail and include a number of examples of validated CE methods for pharmaceutical analysis. Included in Table 4.3 are a number of validated pharmaceutical assay methods. 

In spite of its successes, the grafting, or sprinkhng , of nanoparticles onto a substrate can have limitations with respect to long-term thermal and chemical stabihty under many catalytic reaction conditions. The integration of hetero/nano stmctures into the catalyst support matrix described above, or the covalent attaehment (Margolese 2000 Nakazawa 2008) of the catalytic functionality to the support is a more robust solution, and has been shown to be effective for improving the yield and catalytic performance/stability of homogeneous catalysts (Terry 2007 Nakazawa 2008) and enzymes (Han 2002 Hartman 2010). 

The use of selectively reduced integration to obtain accurate non-trivial solutions for incompressible flow problems by the continuous penalty method is not robust and failure may occur. An alternative method called the discrete penalty technique was therefore developed. In this technique separate discretizations for the equation of motion and the penalty relationship (3.6) are first obtained and then the pressure in the equation of motion is substituted using these discretized forms. Finite elements used in conjunction with the discrete penalty scheme must provide appropriate interpolation orders for velocity and pressure to satisfy the BB condition. This is in contrast to the continuous penalty method in which the satisfaction of the stability condition is achieved indirectly through... 

Rawlings etal. (1992) analysed the stability of a eontinuous erystallizer based on the linearization of population and solute balanee. Their model did not depend on a lumped approximation of partial differenee equations and sueeess-fully predieted the oeeurrenee of sustained oseillations. They demonstrated that simple proportional feedbaek eontrol using moments of CSD as measurements ean stabilize the proeess. It was eoneluded that the relatively high levels of error in these measurements require robust design for effeetive eontrol. 

The class I FruA isolated from rabbit muscle aldolase (RAMA) is the aldolase employed for preparative synthesis in the widest sense, owing to its commercial availability and useful specific activity of 20 U mg . Its operative stability in solution is limiting, but the more robust homologous enzyme from Staphylococcus carnosus has been cloned for overexpression [87], which offers unusual stability for synthetic purposes. Recently, it was shown that less polar substrates may be converted as highly concentrated water-in-oil emulsions [88]. 

However, pMBCl 42 has a thermal stability issue and is expensive (Aldrich price 25 g for 69.90 the largest bottle). On the other hand, pMBOH 43 is stable and economically viable (Aldrich price 500 g for 84.90 the largest bottle). It was found that mono-N-alkylation of 36 proceeded well by slow addition (over 3 h) of 43 to a solution of 36 in acetonitrile in the presence of a catalytic amount of acid (p-TsOH) at 70 °C, as shown in Scheme 1.16. Slow addition of alcohol 43 minimized the self-condensation of 43 to form symmetrical ether 44, which was an equally effective alkylating agent. The product 41 was then directly crystallized from the reaction mixture by addition of water and was isolated in 90% yield and in >99% purity. A toluene solution of 41 can be used for the next reaction without isolation but the yield and optical purity of the asymmetric addition product were more robust if isolated 41 was used. In general, the more complex the reaction, the purer the starting materials the better. 

The question of the stability of the biomolecules is a vital one. Could they really have survived the tremendous energies which would have been set free (in the form of shock waves and/or heat) on the impact of a meteorite Blank et al. (2000) developed a special technique to try and answer this question. They used an 80-mm cannon to produce the shock waves the shocked solution contained the two amino acids lysine and norvaline, which had been found in the Murchison meteorite. Small amounts of the amino acids survived the bombardment , lysine seeming to be a little more robust. In other experiments, the amino acids aminobutyric acid, proline and phenylalanine were subjected to shock waves the first of the three was most stable, the last the most reactive. The products included amino acid dimers as well as cyclic diketopiperazine. The kinetic behaviour of the amino acids differs pressure seems to have a greater effect on the reaction pathway than temperature. As had been recognized earlier, the effect of pressure would have slowed down certain decomposition reactions, such as pyrolysis and decarboxylation (Blank et al., 2001). 

Some important parameters for testing the robustness of TLC methods include the stability of analyte in the solution being analyzed and on the plate before and... 

The weak interactions that may exist between group 2 cations and anionic hydrocabyl ligands are demonstrated in the metal-in-a-box compounds such as [M(THF)6][Me3Si(fluorenyl)]2 (M = Ca 159 or Mg), which are formed by the addition of THF to solutions of the bis(fluorenyl) complexes in non-polar solvents. The box may be completed by the presence of aromatic molecules, as in 159 (Figure 84). The disruption of the metal-carbon bonds is thought to stem from a combination of robust M-THF interaction, the stability of the free [Me3Si(fluorcnyl)] ion, and the formation of numerous C-H- -7r interactions between THF and the anions. These and related examples are reviewed elsewhere. 

Further discussion of method validation can be found in Chapter 7. However, it should be noted from Table 11 that it is frequently desirable to perform validation experiments beyond ICH requirements. While ICH addresses specificity, accuracy, precision, detection limit, quantitation limit, linearity, and range, we have found it useful to additionally examine stability of solutions, reporting threshold, robustness (as detailed above), filtration, relative response factors (RRF), system suitability tests, and where applicable method comparison tests. 

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