Quality control screening methods

It should be pointed out that when using ethidium bromide the sensitivity of the assays varies depending on the physical state of the nucleic acids (see Table I). Ethidium does not discriminate between RNA and DNA, although dyes are available which bind DNA exclusively, so the relative amounts of each may be determined by taking two sets of measurements. Alternatively, nucleases (DNA-ase or RNA-ase) can be used to exclusively remove one or the other in a mixture. Nucleic acids from different sources (see Table II) also show a variation in sensitivity, and the fluorescence assay lacks the selectivity of the hybridization technique. Nevertheless, for rapid screening or quality-control applications the fluorescence assay is still the method of choice. 

Today an increasing importance of qualitative analysis can be stated in certain fields. This is due to an increasing number of materials under study, especially active agents of interest on the one hand, and the many and diverse ways of synthesis (e.g., by combinatorial chemistry) on the other hand as well as the increasing demands on quality. Because analytical laboratories in research and routine control would be overtaxed in their capacity if full quantitative analyses were done generally, screening methods become more and more significant. 

In the new vision, assay cycle time is dramatically reduced and the criteria used to measure assay acceptability are matched to sample type. Early screening samples may be assayed using simple methods and minimum numbers of standards. Samples from early preclinical PK studies in rats and other species may require additional standards. Finally, for PK studies performed in the lead characterization phase, one might add quality control (QC) samples. One set of rules for non-GLP assays has been codified in a recent publication.16 These rules make it possible to match the assay cycle time with the in-life cycle time in order to minimize the total discovery cycle time. 

Sieves are used in screen, or sieve, analysis. This is an inexpensive and reliable method for classifying larger particles based on size and mass. Screen analyses are generally used for quality control and analytical work and find use in a wide variety of industries. They are not suitable for emulsions, sprays, or very fine powders (<0.05 mm in diameter). 

For the dissolution test to be used as an effective drug product characterization and quality control tool, the method must be developed with the various end uses in mind. In some cases, the method used in the early phase of product and formulation development could be different from the final test procedure utilized for control of the product quality. Methods used for formulation screening or BA and/or bioequivalency evaluations may simply be impractical for a quality control environment. It is essential that with the accumulation of experience, the early method be critically re-evaluated and potentially simplified, giving preference to compendial apparatus and media. Hence, the final dissolution method submitted for product registration may not necessarily closely imitate the in vivo environment but should still test the key performance indicators of the formulation. 

Another RP-HPLC technique has been applied for the determination of synthetic food dyes in soft drinks with a minimal clean-up. Separation of dyes was obtained in an ODS column (150 x 4 mm i.d. particle size 5 pm). Solvents A and B were methanol and 40 mM aqueous ammonium acetate (pH = 5), respectively. Gradient conditions were 0-3 min, 10 per cent A 3-5 min, to 25 per cent A 5-8 min, 25 per cent A 8-18 min, to 75 per cent A 18-20 min, 75 per cent A. The flow rate was 1 ml/min and dyes were detected at 414 nm. The separation of synthetic dyes achieved by the method is shown in Fig. 3.35. The concentrations of dyes found in commercial samples are compiled in Table 3.21. The quantification limit depended markedly on the type of dye, being the highest for E-104 (4.0 mg/1) and the lowest for E-102 and E-110 (1.0 mg/1). The detection limit ranged from 0.3 mg/1 (E-102 and E-110) to 1.0 mg/ml (E-104 and E-124). It was suggested that the method can be applied for the screening of food colourants in quality control laboratories [113]. 

Gunter, B., Brideau, C., Pikounis, B., and Liaw, A., Statistical and graphical methods for quality control determination of high-throughput screening data, J. Biomol. Screen., 8, 624, 2003. 

Accordingly, it would be desirable for the alkaline solubilization sampling atomic spectrometric procedures to be accepted both as a routine quality control technique and/or as a screening approach in different processes involving foodstuffs. In this respect, the reduced sample manipulation, the low turnaround time and the relative low cost are primary merits. While single-element determinations using methods such as AAS will continue to play an important role in this Feld, multielement and multiisotope measurements will play an ever more important role in food science in the years to come. 

Generally, the analysis of environmental pollutants is considered as a necessary expense that is performed solely if stated by law. With less expensive screening methods and automated modern equipment to analyze suspect samples, the cost of analysis will become much lower. Hence, the attitude towards QA would most probably be more positive and the analytical work much more reliable for the customers. This also strengthens the international competitiveness of European producers. The credibility of the entire monitoring chain (screening methods, reference and standardized methods, as well as CRMs for the quality control of these methods) lies in the adequacy and integration of all three levels of the system. The adequate development and validation of methods is a prerequisite for a harmonized measurement system [80]. 

Processes for the manufacture of SB s were discussed focusing on the emulsification of oils into aqueous suspensions. Quality control and test methods to accommodate the needs of process control as well as screening tests in the development process were reviewed. 

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