Analytical procedure

Analytical procedures and references should be available if the analytical procedure used is in the current revision of an official compendium or another FDA-recognized standard reference (e.g., AO AC International Book of Methods), and the referenced analytical procedure is not modified. However, the validated analytical procedures for novel excipients should be provided. 

ICH Q6B Specifications Test Procedures and Acceptance Criteria for Biotechnological/Biological Products. 

Laboratory controls should include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures to ensure that raw materials and containers conform to established standards of quality and purity. Specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms, including any minor changes, should be updated by the appropriate organizational unit and reviewed and approved by the QC unit. Laboratory controls should be followed and documented at the time of performance. Deviations from written specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms should be documented and justified. 

Procedures should be established to determine conformance to appropriate written specifications for the acceptance of each lot of raw material, containers, intermediates, and APIs. Such procedures should also cover appropriate sampling and retesting of any materials used in the manufacturing or holding of an intermediate or API that are subject to deterioration or degradation. Laboratory test samples should be representative, properly handled, and adequately identified. 

Analytical reagents used in testing the excipients should be prepared and labeled following established procedures. Retest or expiration dates should be used, as appropriate, for analytical reagents, or standard solutions. Analytical methods should be validated unless the method employed is set forth in the current revision of the United States Pharmacopeia/National Formulary, Association of Official Analytical Chemists (AOAC), Book of Methods, or other recognized standard references, or detailed in the Drug Master File or approved New Drug Application and are used unmodified. 

Analytical Procedures.—Methods have been described for determining saccharin by chromatographic, u.v., and A -ray fluorescence spectrometric 

Quantitative precipitation procedures cannot be applied to a general study of the carbonyl-bisulfite addition reaction involving sugars because of unfavorable solubility characteristics of the products which make their. separation from the unreacted sugars difficult or impossible. 

Volumetric methods are applicable to the analysis of sugar-bisulfite addition compounds, since, being products of a completely reversible reaction, they can be separated into their components stoichiometrically in a reaction system readily amenable to detection of the desired equivalence point within an analytically practical period of time. Attainment of acceptable precision is dependent on proper significance being attributed to factors which may affect the equilibrium rates namely, temperature, 

A procedure satisfactory for the examination of a model system (pure sugar and bisulfite) may not be suitable for examination of practical mixtures. This condition arises because of the possibihty that such compositions as are encountered in the food industry may be highly colored (and thus render end-point observations invalid) or so complicated in composition that the direct approach useful for a model system is totally inadequate. As a result, several general volumetric methods of variable utility in food compositions have been proposed. These include  

It must therefore be concluded that, although some method of this type is indeed desirable, great care should be exercised in establishing satisfactory precision and in interpreting the results. 

Special methods for handling analytical problems frequently are useful. Most of these are described in Chapter 9 and are mentioned here as a reminder. Some of the more common special techniques that can be used, in addition to scale expansion described above, include sampling bracketing, standard addition, and dilution methods. 

For detection of intoxication with OPr, many different analytical methods have been reported. One alternative is to measure the cholinesterase activity, because an acute intoxication is characterized by a 20% decrease in acetylcholinesterase activity. Another approach includes the determination of the unmetabolized OPi in blood or other tissues of 

In addition to the specific acetylcholinesterase that is situated in the erythrocytes, an unspecific cholinesterase called pseudo-cholinesterase exists in plasma. This unspecific cholinesterase hydrolyzes the molecule ACh significantly slower than other cholinesterases, which is why the activity of this cholinesterase is of less importance for an intoxication with OPi. Nonetheless, the measurement of the esterase activity comprises both esterases, which results in misleading data. 

Methods for the detection of cholinesterase activity can generally be divided into four groups, electrometric, colorimetric,titrimetric and tintometric methods, with the last being the one mainly used in the field. The colorimetric method developed by Ellman et al. is the most frequently used procedure. Titrimetry is extremely accurate and precise, but rarely used because of its high cost and complexity. Electrometric methods are less sensitive than colorimetric methods and less accurate than titrimetric methods. 

The colorimetric method is based on the hydrolysis of the substrate acetylthiocholine to acetate and thiocholine as performed by the cholinesterase. Thiocholine is then reacted with 5,5 -dithiobis(2-nitrobenzoic acid) (DTNB) to form a yellow anion (5-thio-2-nitrobenzoate). The latter is quantitated by spectrometric analysis at 405 nm, with the concentration being proportional to the cholinesterase activity in the given sample. Also for a few days postmortem the cholinesterase activity in different tissues is measurable.  

Despite the advantages of biologically monitoring the exposure to pesticides via the degree of cholinesterase inhibition, the enormous intra- and inter-individual variations in 

This section intends to give a survey of the more common analytical methods used in the determination of chromium in biological materials. The criteria which will be evaluated include precision, sensitivity, specificity and speed of analysis. 

The yearly review articles in the Journal of Analytical Atomic Spectrometry provide an excellent follow up of the literature since 1985 (Brown et al., 1986, 1987, 1988, 1989 Crews et al., 1990, Branch et al., 1991, Taylor et al., 1992 Taylor et al., 1993). The following text only intends to give the state of the art in the field. 

A survey of the literature showed that graphite furnace atomic absorption spectrometry (GFAAS) is by far the prevalent technique. Flame atomic absorption spectrometry (FAAS) has been superseded by GFAAS. The list of the other methods includes inductively 

The most difficult Cr determinations are those at the hq and ng per kg levels, as present in body fluids. Such analyses are not only prone to many errors due to contamination, but also requires sensitivities below the detection limit of many methods. The jwg/kg levels of e.g. soft tissues pose lesser problems than the mg/kg amounts of other specimens (food, hair, bone). 

The application of AAS to the assessment of Cr in biological specimens has been extensively reviewed by Tsalev (1984) covering the literature from 1955 tiil 1981, and the state of the art on chromium determinations in environmental and biological samples by Rubio et al. (1992). 

The unsaturated compounds whose additions have been the object of kinetic study are so numerous and diversified that several analytical methods have been used to follow the reactions. 

For processes in the gas phase, static systems (constant volume and temperature) have been mostly used, and the manometric method has been widely employed for Diels-Alder reactions and for 1,2-cycloadditions pressure measurements were associated with gravimetric, infrared or gas-chromatographic analyses whenever required by the presence of more than one product. For Diels-Alder reactions only nonmanometric methods were used, either weighing the producF or chemical analysis of iF, or gas chromatography of reactants and product. 1,2-Cyclo self-addition of gaseous benzyne has been kinetically followed by uv spectroscopy- -.  

Reactions in the pure liquid phase, typically the cyclopentadiene dimerisa-tion, have been sometimes studied by refractometry or dilatometry . In other cases, eithei determination of product and/or reactants has been preferred or the same methods as for reactions in solution were employed. It is worth mentioning that kinetics of a few Diels-Alder reactions were determined by gas-chromatographic analysis of diene, the dienophile being the stationary phase inside the column . 

Most kinetic studies have been carried in solution, and the main analytical methods are listed in Table 1. with a choice of references. Electronic absorption spectroscopy is the most common method, as in other fields of chemical kinetics. Frequently, unless it has been shown by preparative techniques that more than one product is present, analyses by visible-ultraviolet, as well as by infrared spectroscopy, are effected with wavelengths at which absorption by one of the reactants prevails. Gas-volumetric methods are advantageous for analysis of products in special systems where adducts quickly decompose producing small molecules (see also Section I.). Gas chromatography could, in principle, be used to give analysis of both reactants and product(s) however it has been mainly used to determine one of them, as the other methods. 

ANALYTICAL METHODS USED FOR DETERMINATION OF RATE COEFFICIENTS OF 

A number of methods has been used to assay for aldonic acids and aldonolactones. In this Section, these methods will be summarized. Comprehensive coverage of the literature related to analytical techniques has not been attempted in this article. 

Smith and coworkers152 published a relatively complete paper on the thin-layer chromatography, on silica gel, of carbohydrates of low molecular weight. Bancher and coworkers153 reported the thin-layer chromatography of degradation products of carbohydrates, including aldonic acids and aldonolactones. 

The preparation of volatile derivatives of carbohydrates has permitted the development of useful gas-liquid chromatographic analyses 

The volatility of the trimethylsilyl derivatives of the aldonolactones and related carbohydrates has made these derivatives suitable for use in mass spectrometry.161,162 Petersson and coworkers161,162 reported the mass spectra of a variety of trimethylsilyl derivatives of aldonolactones, including the spectrum of 54. 

Other derivatives of aldonolactones and alditols that have found some use in g.l.c. are trifluoroacetates156 and methyl ethers.163 

The following is a general method for groundwater and surface water samples. Unique interferences in particular samples may require modification of this method. If mod-iflcations are necessary, they should be fully documented in the raw data. 

Samples are generally prepared and analyzed in sets of 30 that include at least one control and one fortified control water sample. Optima-grade bottled water may be used as the matrix for the controls and the laboratory-fortified samples for all water types. Depending on the appearance of the samples, filtration may be required. 

Groundwater and raw surface water are typically filtered through a 0.45- xm filter before analysis. This is not generally required of finished surface water. 

Approximately 1-2 mL of the sample is transferred directly into an autosampler vial for LC/MS/MS analysis. 

The calibration curve is generated by plotting the peak area of each analyte in a calibration standard against its concentration. Least-squares estimates of the data points are used to define the calibration curve. Linear, exponential, or quadratic calibration curves may be used, but the analyte levels for all the samples from the same protocol must be analyzed with the same curve fit. In the event that analyte responses exceed the upper range of the standard calibration curve by more than 20%, the samples must be reanalyzed with extended standards or diluted into the existing calibration range. 

League table published by the British povemment s health departments, showing tar and nicotine yields for cigarettes. (Reproduced with acknowledgement to the copyright owner) 

The filter disc is transferred to a stopperred flask containing ethanol and propan-2-ol, and shaken to extract the water present which is then determined by gas-liquid chromatography the quantitity of water present is calculated from the ratio of the areas of the peaks for water (unknown) and ethanol (internal standard). The alkaloids are extracted from the filter disc using sulphuric acid and determined by a specially developed autoanalyser procedure based on the Koenig reaction this is shown schematically in Fig. 21. Since the procedure was developed specially for this application, results obtained from it were compared closely with those produced by the traditional manual method, a steam distillation technique, before it was adopted as a standard method. 

Most studies on the ATR are executed using a mineral acid such as HC1 as acidulant (Greenacre et al., 2003). Studies also typically measure survival of cells at an arbitrary time as indicators of ATR, which as a result ignores 

In general, light isotopes are more mobile and more affected by such processes than heavy isotopes. The isotope fractionation that occurs during these processes is indicated by the fractionation factor a which is defined as the ratio Ra of the heavy to the light isotopes in one compound or phase A divided by the corresponding isotope ratio Rb for the compound or phase B  

For example, the fractionation factor for the exchange of 0 and between water and calcium carbonate is expressed as  

Because isotopic fractionation factors are close to 1, they can be expressed in %o with the introduction of the s-value defined as 

For geochemical purposes, the dependence of isotope fractionation factors on temperature is the most important property. In principle, fractionation factors for isotope exchange reactions are also slightly pressure-dependent, but experimental studies have shown the pressure dependence to be of no importance within the outer earth environments (Hoefs 2004). Occasionally, the fractionation factors can be calculated by means of partition functions derivable from statistical mechanics. However, the interpretation of observed variations of the isotope distribution in nature is largely empirical and relies on observations in natural environments or experimental results obtained in laboratory studies. A brief summary of the theory of isotope exchange reactions is given by Hoefs (2004). 

NIST 951 Searles Lake Borax b/ °b 4.04558 0.00033 NIST 951 (boric acid) 0.25 

Determination of a (U-Th)/He age involves three steps measurement of grain dimensions for determination of the a-ejection correction, measurement of He content, and measurement of U and Th content. We routinely measure all three quantities on a single aliquot, which is frequently a single crystal. Use of a single aliquot eliminates uncertainties that arise from grain-to-grain heterogeneity, e.g., in U and Th content. The current technique we use at Caltech is described below. Broadly similar techniques are in use in several other laboratories. 

Measurement of the evolved He is made by peak height comparison with standard gases on sector-type mass spectrometers such as the MAP 215-50 and VG-3600 (e.g.. Wolf et al. 1996a, Warnock et al. 1997), or by He isotope dilution (ID) on a quadrupole mass spectrometer (QMS). We find that the precision and sensitivity of the ID-QMS technique are superior to those of the sector MS-peak height method. Reproducibility of gas standards suggests that for typical amounts of He evolved from a sample (e.g., of order 1 x 10 cc STP), the ID-QMS technique has a precision of -0.5% (la). The accuracy of this measurement depends on the accuracy of the standard used for calibration, which is probably better than 1% when capacitance manometry is used. 

Upon removal from the vacuum chamber, samples are dissolved in acid (HNO3 for apatite, HCl for monazite and xenotime) and spiked for U and Th analysis. At Caltech we spike with U and Th and analyze U and Th isotope ratios on a Finnigan Element double-focusing inductively-coupled plasma mass spectrometer. The accuracy and precision of these measurements is typically better than 0.5%. 

In some cases we have observed substantially larger inter-aliquot variability. We suspect that in some cases this age spread results from a violation of the assumption of parent nuclide homogeneity on which the a-ejection correction is based (see above). In other cases it probably reflects differences in He closure temperature from grain to grain coupled with a thermal history that magnifies such differences. In still other cases, mineral inclusions are likely the problem. The latter two possibilities are described below. 

As described here the (U-Th)/He method is an absolute dating technique based on fundamental measured quantities rather than comparisons to independently dated materials. Our best estimate of the accuracy of He age determinations is 2% (2o). Although He age standards have not yet been established, support for approximately this degree of accuracy comes from analyses of Durango apatite, and Fish Canyon titanite and zircon (House et al. 2000, Reiners and Farley 2002). Similarly, monazite analyses of a rapidly cooled Oligocene ash flow tuff from SE Peru (Mac-83) yield an average age of 23.98 0.6 Ma (unpublished) that is in agreement with the monazite Th-Pb age of 24.21 0.10 Ma (Villeneuve et al. 2000). 

If only class 3 solvents are present, a non-specific method such as loss of drying may be used. In the other eases a seleetive method (e.g., GC) is required. Especially if solvents of class 2 and class 3 are present at greater than their option 1 limits or 0.5 %, respectively, they should be identified and quantified. 

Clean all glass- and plastic-ware with a brush and a detergent solution followed by a thorough rinse with water. The detergent must be stringently tested for phosphate. Glassware used for the colour development should be reserved exclusively for phosphate determination. 

The blue phosphomolybdic complex, being a colloid, has a tendency to stick as a thin film on the walls of a cuvette. This film can be removed by rinsing with dilute sodium or potassium hydroxide solutions followed by a thorough rinse with water. 

Add 1 mL of ascorbic acid (reagent 4) and 1 mL of mixed reagent (reagent 6) to 50 mL of sample. Mix thoroughly after each reagent addition. 

The absorbance of the blue phosphorus complex reaches a maximum in a few minutes and stays almost constant for many hours. However, the absorbances should be read within 10-30 min, using a wavelength of 880 nm. This determination, on an unfiltered sample, gives the amount of dissolved inorganic phosphate ions in true solution and probably also includes a small fraction of those ions that are adsorbed onto particles and subsequently dissolved by the acid in the mixed reagent. The latter fi-action is not included when a filtered sample is analysed. 

The manifold in Fig. 10-6 requires a sample time of about 2.5 min (4mL sample) to provide a steady-state peak. Heating of the 24 turns reaction coil to 37 °C accelerates the reaction independent of the environmental temperature. Hiis aUows reduction of the reaction coil to 19 turns or the sample time to about 2min (3.2mL sample volume). 

There are two principal means of sample introduction for isotopic analysis by MC-ICP-MS in geo- and cosmochemistry. Most common is the technique of solution nebulization, whilst laser ablation (LA) systems have been applied for in situ isotope ratio measurements [32]. As such, MC-ICP-MS complements both the TIMS and SIMS methodologies, which are the most common alterative methods for bulk sample and in situ isotopic analysis, respectively, in cosmochemical research. 

The application of LA-MC-ICP-MS for isotopic measurements (see also Chapters 2 and 4) was first pioneered in the 1990s [41-43], but although the technique 

In contrast, the application of solution nebulization in conjunction with MC-ICP-MS now readily rivals or even surpasses the importance of TIMS for isotopic analysis of metallic and metalloid elements in bulk meteorite samples. Invariably, such analyses encompass (i) sample dissolution, most often by add digestion, and (ii) a highly selective separation of the analyte element from the bulk sample matrix, typically by one or several stages of column chromatography. Such separations are carried out prior to isotopic analysis of both major elements (e.g.. Mg, Si, Fe) and trace constituents, primarily to ensure that spectral interferences and matrix effects are reduced to either insignificant or at least tolerable levels. In addition, the chemical isolation procedure also acts as a preconcentration method, which allows the isotopic analysis to be carried using solutions that feature element concentrations that are optimized for precise data acquisition. 

Isotopic analysis in cosmochemistry has further profited immensely from instrumental improvements that were developed over the last decade, including new skimmer cone geometries, improved desolvation nebulizer systems, and the use of higher capacity vacuum pumps for the expansion chamber. These 

For instruments operating at lower magnetic fields there is obviously a loss in sensitivity and spectral resolution with respect to the instrument described above. Consequently, the type of problems which can be solved with such less advanced instruments is restricted. Verification of the identity of unknown carbohydrate chains on the basis of comparison with standard reference data sets is possible with 200-360 MHz iH-NMR instruments. 

The investigations carried out in the authors laboratory were supported by the Netherlands Foundation for Chemical Research (SON) with financial aid from the Netherlands Organization for the Advancement of Pure Research (ZWO). 

Berliner, L. J., Reuben, J. (eds.), 1978 Biological Magnetic Resonance, Vol. 1. New York Plenum Press. 

Breitmaier, E., Voelter, W., 1974 NMR Spectroscopy. Weinheim Verlag Chemie. 

Jardetzky, O., Roberts, G. C. K., 1981 NMR in Molecular Biology. New York Academic Press. 

In order to study the toxicokinetics of sulfur mustard, a method to determine the compound in biological matrices (blood and tissues) is needed, preferably with a sensitivity that allows quantitative analysis below the level of toxicological relevance. In several studies, C-labeled sulfur mustard has been used, which allows for convenient and sensitive analysis, but since only radioactivity is measured, the identity of the measured compound(s) is not confirmed, which may be considered a drawback of this approach. 

Sulfur mustard can be extracted from blood and tissue samples via liquid-liquid or solid phase extraction (SPE). The absolute recovery of sulfur mustard via liquid-liquid extraction with ethyl acetate appeared to be higher (80-90%) than with SPE [ca. 70%). Furthermore, the selectivity of SPE was no better than that of liquid-liquid extraction. The addition of sodium chloride, advocated by Maisonneuve et al. (1993) to avoid hydrolysis to hemi-mustard and thiodiglycol, did not appear to be necessary. Fully deuterated (dg) sulfur mustard appeared to be an excellent internal standard, since the recovery of sulfur mustard relative to the deuterated internal standard was 99% under all extraction conditions. No problems with respect to the stability of sulfur mustard in blood samples were encountered when the samples were extracted immediately after being drawn from the animal. 

---

The choice between X-ray fluorescence and the two other methods will be guided by the concentration levels and by the duration of the analytical procedure X-ray fluorescence is usually less sensitive than atomic absorption, but, at least for petroleum products, it requires less preparation after obtaining the calibration curve. Table 2.4 shows the detectable limits and accuracies of the three methods given above for the most commonly analyzed metals in petroleum products. For atomic absorption and plasma, the figures are given for analysis in an organic medium without mineralization. 

The standard analytic procedure involves calculating the orthogonal transformation matrix T that diagonalizes the mass weighted Hessian approximation H = M 2HM 2, namely... 

Many stereoselective reactions have been most thoroughly studied with steroid examples because the rigidity of the steroid nucleus prevents conformational changes and because enormous experience with analytical procedures has been gathered with this particular class of natural products (J. Fried, 1972). The name steroids (stereos (gr.) = solid, rigid) has indeed been selected very well, if one considers stereochemical problems. We shall now briefly point to some other interesting, more steroid-specific reactions. 

An analytical procedure is often tested on materials of known composition. These materials may be pure substances, standard samples, or materials analyzed by some other more accurate method. Repeated determinations on a known material furnish data for both an estimate of the precision and a test for the presence of a constant error in the results. The standard deviation is found from Equation 12 (with the known composition replacing /x). A calculated value for t (Eq. 14) in excess of the appropriate value in Table 2.27 is interpreted as evidence of the presence of a constant error at the indicated level of significance. 

If improvement in precision is claimed for a set of measurements, the variance for the set against which comparison is being made should be placed in the numerator, regardless of magnitude. An experimental F smaller than unity indicates that the claim for improved precision cannot be supported. The technique just given for examining whether the precision varies with the two different analytical procedures, also serves to compare the precision with different materials, or with different operators, laboratories, or sets of equipment. 

Subsection of the analytical approach to problem solving (see Eigure 1.3), of relevance to the selection of a method and the design of an analytical procedure. 

Several texts provide numerous examples of analytical procedures... 

Kirchner, C. J. Estimation of Detection Limits for Environmental Analytical Procedures, In Currie, L. A., ed. Detection in Analytical Chemistry Importance, Theory and Practice. American Chemical Society Washington, DC, 1988. 

Several types of reactions are commonly used in analytical procedures, either in preparing samples for analysis or during the analysis itself. The most important of these are precipitation reactions, acid-base reactions, complexation reactions, and oxidation-reduction reactions. In this section we review these reactions and their equilibrium constant expressions. 

Two frequently encountered analytical problems are (1) the presence of matrix components interfering with the analysis of the analyte and (2) the presence of analytes at concentrations too small to analyze accurately. We have seen how a separation can be used to solve the former problem. Interestingly, separation techniques can often be used to solve the second problem as well. For separations in which a complete recovery of the analyte is desired, it may be possible to transfer the analyte in a manner that increases its concentration. This step in an analytical procedure is known as a preconcentration. 

In practice, however, any improvement in the sensitivity of an acid-base titration due to an increase in k is offset by a decrease in the precision of the equivalence point volume when the buret needs to be refilled. Consequently, standard analytical procedures for acid-base titrimetry are usually written to ensure that titrations require 60-100% of the buret s volume. 

Let s use a simple example to develop the rationale behind a one-way ANOVA calculation. The data in Table 14.7 show the results obtained by several analysts in determining the purity of a single pharmaceutical preparation of sulfanilamide. Each column in this table lists the results obtained by an individual analyst. For convenience, entries in the table are represented by the symbol where i identifies the analyst and j indicates the replicate number thus 3 5 is the fifth replicate for the third analyst (and is equal to 94.24%). The variability in the results shown in Table 14.7 arises from two sources indeterminate errors associated with the analytical procedure that are experienced equally by all analysts, and systematic or determinate errors introduced by the analysts. 

Spike recoveries on method blanks and field blanks are used to evaluate the general performance of an analytical procedure. The concentration of analyte added to the blank should be between 5 and 50 times the method s detection limit. Systematic errors occurring during sampling and transport will result in an unacceptable recovery for the field blank, but not for the method blank. Systematic errors occurring in the laboratory, however, will affect the recoveries for both the field and method blanks. 

Annotated methods of typical analytical procedures link theory with practice. The format encourages students to think about the design of the procedure and why it works. 

Representative methods link theory with practice. An important feature of this text is the presentation of representative methods. These boxed features present typical analytical procedures in a format that encourages students to think about why the procedure is designed as it is. 

An emphasis on critical thinking. Critical thinking is encouraged through problems in which students are asked to explain why certain steps in an analytical procedure are included, or to determine the effect of an experimental error on the results of an analysis. 

Although isotope-dilution analysis can be very accurate, a number of precautions need to be taken. Some of these are obvious ones that any analytical procedure demands. For example, analyte preparation for both spiked and unspiked sample must be as nearly identical as possible the spike also must be intimately mixed with the sample before analysis so there is no differential effect on the subsequent isotope ration measurements. The last requirement sometimes requires special chemical treatment to ensure that the spike element and the sample element are in the same chemical state before analysis. However, once procedures have been set in place, the highly sensitive isotope-dilution analysis gives excellent precision and accuracy for the estimation of several elements at the same time or just one element. 

Analytical Procedures. Standard methods for analysis of food-grade adipic acid are described ia the Food Chemicals Codex (see Refs, ia Table 8). Classical methods are used for assay (titration), trace metals (As, heavy metals as Pb), and total ash. Water is determined by Kad-Fisher titration of a methanol solution of the acid. Determination of color ia methanol solution (APHA, Hazen equivalent, max. 10), as well as iron and other metals, are also described elsewhere (175). Other analyses frequendy are required for resia-grade acid. For example, hydrolyzable nitrogen (NH, amides, nitriles, etc) is determined by distillation of ammonia from an alkaline solution. Reducible nitrogen (nitrates and nitroorganics) may then be determined by adding DeVarda s alloy and continuing the distillation. Hydrocarbon oil contaminants may be determined by ir analysis of halocarbon extracts of alkaline solutions of the acid. 

Because the higher alcohols are made by a number of processes and from different raw materials, analytical procedures are designed to yield three kinds of information the carbon chain length distribution, or combining weight, of the alcohols present the purity of the material and the presence of minor impurities and contaminants that would interfere with subsequent use of the product. Analytical methods and characterization of alcohols have been summarized (13). 

Dual solvent fractional extraction (Fig. 7b) makes use of the selectivity of two solvents (A and B) with respect to consolute components C and D, as defined in equation 7. The two solvents enter the extractor at opposite ends of the cascade and the two consolute components enter at some point within the cascade. Solvent recovery is usually an important feature of dual solvent fractional extraction and provision may also be made for reflux of part of the product streams containing C or D. Simplified graphical and analytical procedures for calculation of stages for dual solvent extraction are available (5) for the cases where is constant and the two solvents A and B are not significantly miscible. In general, the accurate calculation of stages is time-consuming (28) but a computer technique has been developed (56). 

In the United States the analytical methods approved by most states are ones developed under the auspices of the Association of Official Analytical Chemists (AOAC) (3). Penalties for analytical deviation from guaranteed analyses vary, even from state to state within the United States (4). The legally accepted analytical procedures, in general, detect the solubiUty of nitrogen and potassium in water and the solubiUty of phosphoms in a specified citrate solution. Some very slowly soluble nutrient sources, particularly of nitrogen, are included in some specialty fertilizers such as turf fertilizers. The slow solubihty extends the period of effectiveness and reduces leaching losses. In these cases, the proportion and nature of the specialty source must be detailed on the labeling. 

Analytical Procedures for Fluoride Analyses Orion Research Inc., Boston, Mass., 1990—1991. 

Analytical Procedures. Oxygen difluoride may be determined conveniently by quantitative appHcation of k, nmr, and mass spectroscopy. Purity may also be assessed by vapor pressure measurements. Wet-chemical analyses can be conducted either by digestion with excess NaOH, followed by measurement of the excess base (2) and the fluoride ion (48,49), or by reaction with acidified KI solution, followed by measurement of the Hberated I2 (4). 

Plots of the bursting pressures of the Ni—Cr—Mo cylinders (EN 25) vs k derived from equations 16 and 17 show that neither equation is in such good agreement with the experimental results as is the curve derived from Manning s theory. Similar conclusions have been reached for cylinders made of other materials which have been tested (16). Manning s analytical procedure may be programmed for computation and, although torsion tests are not as commonly specified as tension tests, they are not difficult or expensive to carry out (20). 

Analysis. Lithium can be detected by the strong orange-red emission of light in a flame. Emission spectroscopy allows very accurate determination of lithium and is the most commonly used analytical procedure. The red emission line at 670.8 nm is usually used for analytical determinations although the orange emission line at 610.3 nm is also strong. Numerous other methods for lithium determinations have been reviewed (49,50). 

Ozone can be analyzed by titrimetry, direct and colorimetric spectrometry, amperometry, oxidation—reduction potential (ORP), chemiluminescence, calorimetry, thermal conductivity, and isothermal pressure change on decomposition. The last three methods ate not frequently employed. Proper measurement of ozone in water requites an awareness of its reactivity, instabiUty, volatility, and the potential effect of interfering substances. To eliminate interferences, ozone sometimes is sparged out of solution by using an inert gas for analysis in the gas phase or on reabsorption in a clean solution. Historically, the most common analytical procedure has been the iodometric method in which gaseous ozone is absorbed by aqueous KI. 

The therapeutically active dmg can be extracted from plant or animal tissue, or be a product of fermentation (qv), as in the case of antibiotics. Frequentiy, it is synthesized and designed to correlate stmcture with therapeutic activity. Pharmacologic activity is first tested on laboratory animals. When the results ate encouraging, physical and chemical properties are determined in the so-called preformulation stage, and analytical procedures are developed for quahty control (see Qualityassurance/qualitycontrol). 

In most analytical procedures for determining the total phosphoms content (normally expressed in terms of P20 ), the phosphates are converted to the orthophosphate form. Typically, condensed phosphates are hydrolyzed to orthophosphate by boiling in dilute mineral acid (0.1 N). The orthophosphate is then deterrnined by gravimetric or spectrophotometric methods. For gravimetric deterrnination, insoluble phosphomolybdates (or magnesium ammonium orthophosphate) is formed. 

APHA color is deterrnined using ASTM D1209 percent water is deterrnined by Kad Eischer titration following ASTM E203. Detailed analytical procedures are available in the fiterature (1) or from producers. 

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. 

---