Analyze residuals

The response siuface model is used as a map of the explored domain and will, hopefully, give a reliable description. The model should therefore withstand all possible diagnostic tests. An analysis of the residuals, as was discussed in Chapter 6, may often be informative and it is advisable always to make the following plots as a safe-guard against potential inadequacies of the model  

Example Optimization of a synthetic procedure by response surface modelling from a central composite design. Enamine synthesis by a modified TiCl -method 

A standard method for enamines synthesis from carbonyl compounds is to heat the parent aldehyde or ketone and a secondary amine in benzene or toluene and to remove the eliminated water by azeotropic distillation. However, this method fails with methyl ketone substrates which are prone to self-condensation imder these conditions. These difficulties could be overcome by a procedure using anhydrous titanium tetrachloride as water scavenger.[6] In the original procedure, titanium tetrachloride was added dropwise to a cold solution of the ketone and the amine, followed by prolonged stirring at room temperature. It was later found that the reaction time could be considerably shortened by a modified procedure, in which the 

For the modified procedure, it was found that the relative amounts of TiCl4/ketone and amine /ketone which should be used to achieve a rapid conversion were highly dependent on the structure of the ketone.[7,8] In the example below, the formation of the morpholine enamine from methyl isobutyl ketone was studied. 

The experimental domain is given in Table 12.4. A uniform precision central composite rotatable design (5 center point experiments) was used. The design and the yields of enamine obtained after 15 minutes are given in Table 12.5. 

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A fully automated instrumental procedure has been developed for analyzing residual corrosion inhibitors in production waters in the field. The method uses ultraviolet (UV) and fluorescence spectrophotometric techniques to characterize different types of corrosion inhibitors. Laboratory evaluations showed that fluorescence is more suitable for field application because errors from high salinity, contamination, and matrix effect are minimized in fluorescence analysis. Comparison of the automated fluorescence technique with the classic extraction-dye transfer technique showed definite advantages of the former with respect to ease, speed, accuracy, and precision [1658],... 

The MHLW recognizes the official analytical methods for inspection and survey of MRLs for crops in the market 112 residue analytical methods have already been established and authorized. MHLW also approves the use of the original analytical methods for the official surveillance by which methods local governments analyze residues as they inspect local commercial farm commodities. In such a case, the reliability of the original analytical methods should be guaranteed as being equivalent to that of the official analytical methods. 

Use may also be determined by examining the way the tools wore when used and by analyzing residues on their surface. 

A Simple and Rapid Assay for Analyzing Residues of Carbamate Insecticides in Vegetables and Fruits Hot Water Extraction Followed by Liquid Chromatography-Mass Spectrometry (from Bogialli et ah, 2004)... 

The determination of OXPHOS activity is best made with the aid of spectrophoto-metric assays [55, 65]. Using a judicious set of electron donors and acceptors, it is possible to measure the activity of MRC complexes either isolated or in combination, as described below. Beside the residual activity of each complex, ratios of their respective activities are of fundamental importance. Indeed, the balance between complexes (the ratio between their activities) determines on the one hand the relative access of each dehydrogenase to the MRC, and on the other hand the amount of superoxides possibly escaping the chain [55]. It is therefore quite important to both analyze residual activities corrected for the variable amount of mitochondria using the citrate synthase as reference enzyme, and the various ratios inside the MRC [66,67]. It is also important to note that enzyme determination is (supposedly at least) done under maximal rate (Vmax) conditions only, often leaving aside any discrete anomalies possibly affecting affinity and regulatory properties. 

Several microbiological methods have been reported for analyzing residues within the groups of sulfonamides, tetracyclines, macrolides, and -lactams in fish tissues however, references for these groups of compounds are limited to sulfadiazine and trimethoprim, oxytetracydine and chlortetracycline, erythromycin, and ampicillin, respectively. 

Bogialli, S., R. Curini, A. Di Corcia, M. Nazzari, and D. Tamburo. 2004. A simple and rapid assay for analyzing residues of carbamate insecticides in vegetables and fruits Hot water extraction followed by liquid chromatography-mass spectrometry. Agric. Food Chem. S2 665-671. 

A methodology was developed to estimate quantities of crop residues that can be removed while maintaining rain or wind erosion at less than or equal to the tolerable soil-loss level. Six com and wheat rotations in the 10 largest com-producing states were analyzed. Residue removal rates for each rotation were evaluated for conventional, mulch/reduced, and no-till field operations. The analyses indicated that potential removable maximum quantities range from nearly 5.5 million dry metric t/yr for a continuous corn rotation using conventional till in Kansas to more than 97 million dry metric t/yr for a corn-wheat rotation using no-till in Illinois. 

The total consumption of formaldehyde for each reaction was estimated by removing two 7 mL aliquots of the reaction mixture and heating these at 60 °C for 2 hours in screw-top glass vials and analyzing residual formaldehyde by the above method. 

The ability of certain soils to sorb the chemical strongly is important in analyzing residues of the chemical in soil. A procedure must be developed which will recover the chemical quantitatively from any soil. Table VII compares extraction from two soils, soil 3 which saturates with 4-amino-3,5,6-trichloropicolinic acid quickly and soil Bi which shows the slow takeup phenomenon. It is apparent that soil Bi, incubated 2 hours, holds the chemical more firmly than soil 3, incubated 5 days, but that hot water will remove most of the chemical from both soils. When soil Bi has been incubated for 28 days, removal of chemical was only 78.7% after three water washes, but further extraction with NaOH increased the recovery to over 99%. Several mild methods of extraction are compared in Table VIII. The same experimental techniques were used here but, instead of determining the extracted 4-amino-3,5,6-trichloropicolinic acid, the washed soil was assayed. A 50-mg. portion of dried, ground soil was suspended in a silica gel medium for scintillation counting and... 

The methods approved for analyzing residual moisture in freeze-dried biological products licensed by the FDA are the gravimetric (loss on drying) method, many... 

Liquid chromatography-mass Spectrometry (LC-MS) and GC-MS were used to analyze the residues from sherds of presumed ancient chocolate vessels from Honduras. Only the residues that had been absorbed into the pottery were extracted and analyzed. Residues were collected by heating sherds in distilled water, meth-ane/methanol, or chloroform/methanol and filtering. The liquids and precipitates that accumulate inside pottery can be preserved because they are bound up in the clay matrix and less susceptible to contamination. 

Crown contacted Hurst, who then analyzed residues from midden sherds from... 

It is important to verify the adequacy of the model in comparison with the measured values, and to analyze residuals after the empirical model is constructed. The adequacy of the model can be assessed by using the so called F-test [37], which compares two types of... 

Several groups have adapted the method to analyze residues in a variety of matrices. Acetic acid (HQAc, 1%) and sodium acetate have been widely used to adjust and maintain pH and promote stability and recovery of base-sensitive residues. HOAc was used to adjust pH by Stubbings and Bigwood to determine residues [sulfonamides, quinolones, (fluoro)quinolones, ionophores, and nitroimidazoles] in chicken muscle. Buffering to acidic conditions improved the extraction efficiency of quinolones. Aeetonitrile extracts were subsequently purified by dSPE (see also Section 4.4.6.1) over Bondesil NH2 sorbent. An aliquot of the extracts was evaporated to dryness and re-dissolved in acetonitrile water (90 10, v/v) before LC-MS/MS analysis. Validation was performed on chicken muscle samples, and matrix-matched standards were used because suppression of the MS response was observed for many of the target analytes. 

Lu et al. described the trace determination of sulfonamide residues in meat with a combination of SPME and LC-MS. Fiber coated with a 65 p,m thickness of polydimethylsiloxane/divinylbenzene (PDMS/DVB) was used to extract sulfonamides at optimum conditions. Analytes were desorbed with static desorption in an SPME-HPLC desorption chamber for 15 min and then determined by LC-MS. The linear range was 50-2000 p-g/kg, with RSD values below 15% (intra-day) and 19% (inter-day) and detection limits 16-39 pg/kg. Some meat samples collected from the local market contained residues of sulfonamides ranging from 66 to 157 pg/kg. The results demonstrated that the SPME-LC-MS system could effectively analyze residues of sulfonamides in meat products. 

Bogialli S, Curini R, Di Corcia A, Lagana A, Mele M, Nazzari M, Simple confirmatory assay for analyzing residues of aminoglycoside antibiotics in bovine milk Hot water extraction followed by liquid chromatography-tandem mass spectrometry, J. Chromatogr. A 2005 1067(l-2) 93-100. 

It is also interesting to mention that SPE on Isolute proved to be a successful procedure for analyzing residual succinic acid in nucleoside derivatives to be used in nucleotide synthesis [291]. According to the developed protocol, almost all nucleoside derivatives are trapped by the sorbent at pH 7 whereas succinic acid is ionized at this pH value and does not bind to the sorbent, so that examining the filtrate with GC—MS allowed safe determination of 0.18-0.24% of the disturbing admixtures of succinic acid in the nucleoside preparations. 

This is, of course, the method of choice which has long been used to determine RS whatever the area of application (pharmaceuticals, polymers, water analysis, etc.). " From the late 70 s to the beginning of the 80 s, there was a large number (or flood) of publications dealing with different possible GC techniques which could be applied for detecting or analyzing residual solvents especially in pharmaceuticals (intermediates of synthesis, drug sub-... 

Assumed risk A specific, analyzed residual risk accepted at an appropriate level of management. Ideally, the risk has had analysis of alternatives for increasing control and evaluation of significance of consequences (SSDC). 

LC-TSP-MS has been successfully applied for detec-tion/confirmation of nicarbazin residues in chicken tissues using negative-ion detection in the SIM mode." LC-TSP-MS in the SIM mode has also been used for quantification of residues of moxidectin in cattle tissues and fat, " and nitroxynil, rafoxanide, and levamisole in muscle." Confirmatory methods based on LC-TSP-MS have fiirther been reported for determination of penicillin G, cephapirin,"" and various penicillin derivatives" in milk. Comparative evaluation of the confirmatory efficiency of LC-TSP-MS and LC—TSP—MS—MS in the assay of maduramycin in chicken fat showed the former approach to be marginally appropriate whereas the latter highly efficient." Tandem LC-MS-MS has also been successfully applied for analyzing residues of chloramphenicol in milk and fish." ... 

Lin and Hsu [58] assessed the value of using NIR spectroscopy to analyze residual moisture in lyophilized protein pharmaceuticals sealed in glass vials. They found that doubling or halving the concentration of a disaccharide used as a lyoprotectant caused significant deviation between NIR and Karl Fischer data because the NIR absorbance of the disaccharide overlapped with the moisture signal. 

We analyze residual stresses around dispersed particles using a simplified model consisting of a spherical particle within a concentric matrix sphere with axial symmetry shown in Fig. 1 to clarify dislocation activities in nanocomposites. Existence of a surrounding interlayer (glass-phase) on the second-phase particle is also considered for analyzing the effects of the interlayer on the stress distributions. 

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