Determinative procedures

As the result of the performed investigations was offered to make direct photometric determination of Nd microgram quantities in the presence of 500-fold and 1100-fold quantities of Mo and Pb correspondingly. The rare earth determination procedure involves sample dissolution in HCI, molybdenum reduction to Mo (V) by hydrazine and lead and Mo (V) masking by EDTA. The maximal colour development of Nd-arsenazo III complex was obtained at pH 2,7-2,8. The optimal condition of Nd determination that was established permit to estimate Nd without separation in solution after sample decomposition. Relative standard deviations at determination of 5-20 p.g of Nd from 0,1 g PbMoO are 0,1-0,03. The received data allow to use the offered procedure for solving of wide circle of analytical problems. 

Information on Concentration and Determination Procedures in Atomic Spectrophotometry, 1992... 

Zanker has presented a graphical technique for determining the fouling resistance (factor) for process or water fluid systems based on selected or plant data measurements, as shown in Figures 10-43A, 10-43B, and 10-43C. The design determination procedure presented by ZankeD is quoted here and used by permission from Hydrocarbon Processing... 

A method should be able both to quantify the amount of marker drug residue present in the sample and to identify the compound unambiguously. Historically, this required two distinct procedures a determinative procedure used to quantify the analyte, and a confirmatory procedure used to unequivocally identify the analyte. The need for two procedures was driven by the limitations of available technology. Most determinative methods over the last two decades have been based on liquid chromatography, usually with ultraviolet (UV)/visible or fluorescence defection. Limitations of cost. 

By definition, the determinative procedure must be able to quantify the concentration of the marker residue. For compounds with a tolerance, it is critical that the analysis be able to determine accurately if the concentration of the marker residue is above or below the tolerance in the target tissue. The CVM guidelines for determinative procedures call for an average recovery >80% with a coefficient of variation (CV) of <10% for marker residue tolerances of lOOpgkg or greater and an average recovery of >60% with a CV of <20% for marker residues with a tolerance below 100 ppb. 

The confirmatory procedure should be developed for the same tissues for which the determinative procedure was developed, preferably using the same extraction procedure as used for the determinative portion of the method. Storage and stability data are necessary for dried or liquid sample extracts if MS analyses of the confirmatory samples are to be conducted in a laboratory other than the laboratory of sample preparation. Analytes present in sample extracts must be stable long enough for the samples to be shipped to the MS laboratory and analyzed. 

One of the primary requirements for methods is that it be practicable [Section 512(b)(1)(G)]. A method that cannot be used in Federal laboratories has no value in the protection of the food supply. Method developers should avoid the use of rare or custom-made equipment, prohibitively expensive equipment, untested technologies, or reagents that are not commercially available. For a determinative procedure, an analysis should not exceed two working days, and methods should have a minimum sample throughput of at least six samples per analyst-day. 

The use of standards prepared in control matrices is typically not allowed for determinative procedures because control tissues are not routinely available to regulatory laboratories. When a matrix effect alters the spectrum or chromatography of an analyte relative to the pure standard, so that confirmatory criteria cannot be met, a control extract containing standard may be substituted for pure standard. Justification, with CVM concurrence, should be provided for confirmatory methods that use fortified control extracts. 

Accuracy (systematic error or bias) expresses the closeness of the measured value to the true or actual value. Accuracy is usually expressed as the percentage recovery of added analyte. Acceptable average analyte recovery for determinative procedures is 80-110% for a tolerance of > 100 p-g kg and 60-110% is acceptable for a tolerance of < 100 p-g kg Correction factors are not allowed. Methods utilizing internal standards may have lower analyte absolute recovery values. Internal standard suitability needs to be verified by showing that the extraction efficiencies and response factors of the internal standard are similar to those of the analyte over the entire concentration range. The analyst should be aware that in residue analysis the recovery of the fortified marker residue from the control matrix might not be similar to the recovery from an incurred marker residue. 

The format for analytical methods proposed as the regulatory method should be clear and should contain all necessary information needed successfully to perform the laboratory steps and calculate the results. The following is a recommended format for a determinative procedure ... 

The method trial process for NADA methods is different to the process for non-NADA methods. However, the validation protocol followed by the participating laboratories and the requirements for acceptance of the method are the same. The trial process also differs for determinative procedures and confirmatory procedures. Determinative procedures are evaluated using the multiple laboratory process, whereas the confirmatory method needs to be evaluated only in a single government laboratory. 

Confirmatory procedures are evaluated differently from determinative procedures because of the different intended uses of the procedure. The primary differences are the testing laboratories and evaluation of the resulting data. Because a confirmatory procedure is needed for legal action, the procedure will be evaluated based on the results obtained in a government laboratory. 

The final difference is that the FDA analyst alone makes the recommendation based on the data for the acceptance of the confirmatory procedure. The conclusion of the analyst stating the suitability of the procedure for confirming the presence of the marker residue is sent directly to the CVM method trial coordinator in the Office of New Animal Drug Evaluation (ONADE) and not back to the sponsor as with the determinative procedure. 

Guidelines for acceptability of NADA and non-NADA methods are the same. For the determinative procedure, the criteria described in Method Criteria for accuracy and precision are used to evaluate data generated at participating laboratories. There are no criteria for accuracy in the analysis of the incurred residue samples however, the overall data set is reviewed to see if there is general agreement between results obtained by contract laboratories and relative to the levels reported in the sponsor s laboratory. 

On the other hand, single-residue methods developed by the applicants give basic information about appropriate cleanup steps and specific determination procedures. In addition, not many laboratories other than those from the applicants are able to test the real solvent extraction efficiency. The reason is that extraction studies need radio-labeled incurred residues instead of fortified samples. Hence enforcement methods provided by the manufacturers accelerate the development of methods which meet the needs of (official) food control laboratories. 

The enforcement methods provided by the applicants give basic information about appropriate cleanup steps and specific determination procedures. Typically, direct use of this developmental work occurred when a GC multi-residue method was found appropriate. Owing to the recent developments in the field of MS/MS with atmospheric pressure ionization, an alternative approach for those compounds that can be analyzed by liquid chromatography (LC) will soon be possible. It is important that some fundamental considerations for such method(s) should be agreed at the outset. Considerations include the most suitable extraction solvents and cleanup steps and some standard HPLC conditions. 

The determination procedure, evaluation and calculation of residues are described in Sections 2.2.5-2.2.1. 

Sample preparation consists of homogenization, extraction, and cleanup steps. In the case of multiresidue pesticide analysis, different approaches can have substantially different sample preparation procedures but may employ the same determinative steps. For example, in the case of soil analysis, the imidazolinone herbicides require extraction of the soil in 0.5 M NaQH solution, whereas for the sulfonylurea herbicides, 0.5M NaOH solution would completely decompose the compounds. However, these two classes of compounds have the same determinative procedure. Some detection methods may permit fewer sample preparation steps, but in some cases the quality of the results or ruggedness of the method suffers when short cuts are attempted. For example, when MS is used, one pitfall is that one may automatically assume that all matrix effects are eliminated because of the specificity and selectivity of MS. 

As the alkylenebis(dithiocarbamates) are not soluble in water or organic solvents, there are two possible procedures to carry out the recovery experiments. The first is to fortify the solid standard onto the untreated sample in the decomposition vessel, and follow the determination procedure as described above. A second option is to... 

The determination procedure is described in Section 2.2.4. The ELISA determination of water samples can be performed directly, such as for imidacloprid in tap water. ... 

There is no other vitamin which exemplifies the interdependence between the human race and microorganisms better than Vitamin B12. Mankind still relies for its very existence upon the capability of a few species of bacteria to synthesize this fascinating coordination complex. A concerted effort is being made in a number of laboratories to determine procedures for the chemical synthesis of this vitamin. However, even the most talented synthetic chemists would have to admit that the organic chemist s lament is applicable to Vitamin B12 ... 

Protein determination procedures using bicinchonic acid were developed by Pierce Chemicals, who hold a patent on the product. The procedure entails the use of a copper-based reagent containing bicinchonic acid. Upon incubation with a protein sample, the copper is reduced. In the reduced state it reacts with bicinchonic acid, yielding a purple colour that absorbs maximally at 562 nm. 

Pressure design of straight-threaded joints shall be based on calculations consistent with design requirements of this Code. These calculations shall be substantiated by testing in accordance with to-be-determined procedures and protocols. The testing shall consider such factors as assembly and disassembly, cyclic loading, vibration, shock, hydrogen embrittlement, thermal expansion and contraction, and other factors to be determined. 

The following loads are computed from free field blast wave parameters. Refer to Chapter 3 for load determination procedure. 

If the reduction of C—C BDEs by captodative substitution is interpreted with the appropriate caution, it can be stated that a conclusive answer as to the existence of a captodative effect in free radicals cannot be derived from these studies, If, furthermore, a consequent error-propagation analysis had been carried out, the outcome might have been that the error limits do not allow a definitive conclusion. However, the results convey a feeling that— regardless of the pros and cons for the different determination procedures— a possible captodative effect will not be great. 

Structure-based drug discovery involves determination of many cocrystal structures with different ligands bound to the same target protein. In such cases, where the structure of the protein is well known, automated structure determination procedures rely on molecular replacement to supply the... 

As with any analytical determination procedure, both quality assurance and quality control issues have to be built into the detection of PPCPs in the environment. For example, analysis of polycyclic musks (PCM) can be easily skewed during analysis as the compound might be present in laboratory soaps and creams, thus coating laboratory glassware used for the analysis. Therefore, programs that are designed to research... 

Exact details of the method can be found in the total dietary fibre determination procedure AOAC Method 991.43 and AACC Method 32-07 (AOAC, 1995 AACC, 2000). 

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