Alternative analytical procedures

The applicant may include in its application alternative analytical procedures to the approved regulatory procedure for testing the drug substance and drug product. However, for purposes of determining compliance with the Act, the regulatory analytical procedure is used. 

For drug substance and drug product, the addition, deletion or revision of an alternative analytical procedure that provides the same or greater level of assurance of the identity, strength, quahty, purity, or potency of the material being tested as the analytical procedure described in the approved application. 

A good separation and identification of, in particular, insecticides with predominantly lipophihc properties, can be realised with TLC. PC (see work of Mitchell [64]) and GC with highly sensitive detectors [15, 40] are used in practice as alternative analytical procedures. In PC, the lower limit of detection of insecticides is about 15—50 g in TLC, as little as 0.05 [xg. Special reference may be made to IR-spectroscopy for identifying insecticides (see under Morris [66]). 

Enzyme immunoassay (EIA) is an alternative analytical procedure to radioimmunoassay which takes full advantage of the specificity and sensitivity that result from the use of an antibody but does not employ a radioactive isotope. 

A concept first used in Ref. 7, where it was called an irregular polygon. An alternative analytical procedure for computing the polygon s coordinates can be found there. 

The ease of hydrolysis of metal alkoxides makes metal analysis a comparatively simple task. In many cases, the metal may be estimated by hydrolysis of a sample in a cmcible, and ignition to the metal oxide. Alternatively, the metal ion may be brought into solution by hydrolysis of a sample with dilute acid, followed by a standard analytical procedure for a solution of that particular metal. If the alcohol Hberated during the hydrolysis is likely to cause interference, it may be distilled from the solution by boiling. 

An alternative metlrod of solution to these analytical procedures, which is particularly useful in computer-assisted calculations, is the finite-difference technique. The Fourier equation describes the accumulation of heat in a thin slice of the heated solid, between the values x and x + dx, resulting from the flow of heat tlirough the solid. The accumulation of heat in the layer is the difference between the flux of energy into the layer at x = x, J and the flux out of the layer at x = x + dx, Jx +Ox- Therefore the accumulation of heat in the layer may be written as... 

Methods developed for on-line technological control have to be tested for the variation of the product composition due to process variations. However, if rugged analytical procedures are developed these multidimensional methods may only require minimal attention during on-line operation. Multidimensional chromatography for the analysis of complex polymer and industrial samples offers chromatogra-phers high productivity and efficiency and is an excellent alternative to off-line methods. 

Information on ship resistance has been determined from large numbers of tests on scale models of ships and from full-size ships, and compilations of these experimental results have been published. For a new and innovative hull form the usual procedure is to construct a scale model of the ship and then to conduct resistance tests m a special test facility (towing tank). Alternatively, analytical methods can provide estimates of ship resistance for a range of different hull shapes. Computer programs have been written based on these theoretical analyses and have been used with success for many ship designs, including racing sailboats. 

During the traditional qualitative inorganic analytical procedure, samples containing the lead and salicylate radicals can lead to the formation and possible detonation of lead picrate. This arises dining evaporation of the filtrate with nitric acid, after precipitation of the copper-tin group metals with hydrogen sulfide. Salicylic acid is converted under these conditions to picric acid, which in presence of lead gives explosive lead picrate. An alternative (MAQA) scheme is described which avoids this possibility. 

The accuracy of an analysis can be determined by several procedures. One common method is to analyze a known sample, such as a standard solution or a quality control check standard solution that may be available commercially, or a laboratory-prepared standard solution made from a neat compound, and to compare the test results with the true values (values expected theoretically). Such samples must be subjected to all analytical steps, including sample extraction, digestion, or concentration, similar to regular samples. Alternatively, accuracy may be estimated from the recovery of a known standard solution spiked or added into the sample in which a known amount of the same substance that is to be tested is added to an aliquot of the sample, usually as a solution, prior to the analysis. The concentration of the analyte in the spiked solution of the sample is then measured. The percent spike recovery is then calculated. A correction for the bias in the analytical procedure can then be made, based on the percent spike recovery. However, in most routine analysis such bias correction is not required. Percent spike recovery may then be calculated as follows ... 

During the last few years, a number of specific monographs for different pharmaceutical products have appeared in pharmacopoeias in which CE is prescribed as one of the analytical procedures. Several comparative studies have been reported in which established analytical procedures described in pharmacopoeial monographs were compared with capillary electrophoretic methods or in which CE was evaluated as a valuable additional technique.Based on the results, some analytical procedures have been replaced by CE-based alternative methods in a number of monographs. For other products, CE has been included in the monograph from the initial version onwards. In addition, CE has been applied... 

Methods have successfully been transferred to various laboratories in inter-company cross-validation exercises for a chiral separation, for an assay of the main component in a formulation and for drug stoichiometry. Revalidation is an alternative to method transfer in case of changes in product composition or analytical procedure (cf. Section I.L). Although a method transfer in CE is not a major difficulty, some aspects have to be considered, especially if a method is transferred to an instrument of another manufacturer. 

It is required for quantitative purity assays, and it must be established across the specified range of the analytical procedure. This can be done, by establishing the recovery rate over the range of the method. Alternatively, a method comparison between a validated method and a new method can be performed. Accuracy can be determined by spiking degraded, aggregated, pure or impure material into a known amount of sample. A theoretical recovery would then be calculated and the spike material analyzed using the chosen method. The actual recovery should then be compared to the theoretical recovery to calculate the accuracy of the method. Accuracy in this case would be reported as percent recovery. 

One alternative regenerating procedure involves the sequential aspiration of the sample and regenerating carrier (Fig. 2.17.B.2), which requires actuating the switching valve in order to restore the sensor. It allows larger sample volumes to be used in order to raise the analyte concentration at the active microzone when highly dilute samples are to be processed (e.g. see [19]). 

An alternative cleanup procedure is the partition of the raw extract, which often contains considerable amounts of lipid material, between an organic and an aqueous sodium hydroxide phase. With this partitioning scheme, the analytes are further fractionated into estrogens and nonestrogens. The presence of phenolic groups in the molecules of estrogens such as diethylstilbestrol and zeranol ensures their complete extraction from organic phases such as chloroform or tert.-butyl methyl ether into the aqueous sodium hydroxide phase (435, 438, 447). Further purification could be accomplished by neutralization of the sodium hydroxide solution and back-extraction of the contained diethylstilbestrol into diethyl ether (435), or adjustment of the pH of the sodium hydroxide solution to 10.6-10.8 and back-extraction of the contained zeranol into a chloroform phase (447). 

A simple analytical procedure will enable us to guide the development of a number of alternative polymethanes. The fields in which we typically work involve the interactions of polymers and water. In environmental and biotechnology applications that will play an important part in our discussions, the association with water is critical to the function of the polymer, and a test to gauge this relationship will be very useful. 

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