Analytical methodologies

The selection and evaluation of analytical methods are discussed in Chapters 14 and 15. It is important to recognize, however, that the initial evaluation of a method often takes place in a setting somewhat more idealized than the production setting. It is therefore desirable to have a start-up period in the service laboratory before test results are to be reported. This period allows tune to (1) discover any additional problems, (2) develop maintenance programs that alleviate those problems, and (3) train a sufficient number of analysts to support the routine service operation. 

The types of information required largely determine the choices of analytical methodology available. Pharmacokinetic studies for new chemical entities 

LC/MS/MS is the preferred means of detection, quantitation, and confirmation of sulfonylurea herbicides in biological and environmental matrices. Therefore, recommendations for establishing and optimizing LC/MS/MS analyses common to all matrices are given first, followed by specific rationales for methods and sample preparation techniques for plant, soil, and water matrices. 

A triple-quadrupole mass spectrometer with an electrospray interface is recommended for achieving the best sensitivity and selectivity in the quantitative determination of sulfonylurea herbicides. Ion trap mass spectrometers may also be used, but reduced sensitivity may be observed, in addition to more severe matrix suppression due to the increased need for sample concentration or to the space charge effect. Also, we have observed that two parent to daughter transitions cannot be obtained for some of the sulfonylurea compounds when ion traps are used in the MS/MS mode. Most electrospray LC/MS and LC/MS/MS analyses of sulfonylureas have been done in the positive ion mode with acidic HPLC mobile phases. The formation of (M - - H)+ ions in solution and in the gas phase under these conditions is favorable, and fragmentation or formation of undesirable adducts can easily be minimized. Owing to the acid-base nature of these molecules, negative ionization can also be used, with the formation of (M - H) ions at mobile phase pH values of approximately 5-7, but the sensitivity is often reduced as compared with the positive ion mode. 

The MS/MS response for each analyte must first be optimized on the specific instrument to be used. This is usually done by infusing a solution of the analyte into the HPLC mobile phase without a column present. The composition of the mobile phase should match that expected at the time of analyte elution within 25%. The instrument is first operated in the LC/MS mode, and the settings for the electrospray interface are 

Column temperature Injection volume Autosampler temperature Flow rate 

6-mm i.d. x 15 cm, Phenomenex Cg analytical column with 3-pm-diameter packing 40 °C 0.100 mL 

Calibration standards of the 18 elanents and a calibration blank were prepared from multielement standards in 2% NaCl + 1% HNO3, using an external linear-through-zero calibration graph. A different blank (1% HNO3) was subtracted from all samples due to the fact that some contaminations were present in 2% NaCl. Concentrations of the six multielement standards were 25, 50,100, 500,1000, and 5000 ppt. 

The instrument was run in the coUision/reaction mode using ammonia (NHj) gas to remove potential polyatomic interferences, because many of the transition elements are susceptible to spectral overlaps from ionic species generated by the plasma argon and the seawater matrix. The major instrument operating parameters are shown in Table 20.3. 

FIGURE 20.2 Schematic of the seaFAST sampling system coupled to an ICP-MS. (Courtesy of Elemental Scientific, Inc.) 

FIGURE 20.3 seaFASTtimeline of automated analysis of seawater versus signal intensity. 

To fully assess the practical, real-world applicability of this automated online chemical pretreatment method, accuracy, detection capability, and stability tests were carried out. Accuracy was evaluated by analyzing a seawater certified reference material. The average of four separate analyses of the NASS 5 ocean seawater are shown in Table 20.4. All the data generated are well within the error of the certified values except for zinc, which is approximately three-fold higher. It is well-recognized that zinc is a notoriously difficult element to determine by ICP-MS because of contamination issues. For that reason, it is likely that the NASS 5 certified reference material (CRM) was contaminated with zinc from an external source before or during the analysis. 

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Suppose you are asked to develop a way to determine the concentration of lead in drinking water. How would you approach this problem To answer this question it helps to distinguish among four levels of analytical methodology techniques, methods, procedures, and protocols. ... 

There is an obvious order to these four facets of analytical methodology. Ideally, a protocol uses a previously validated procedure. Before developing and validating a procedure, a method of analysis must be selected. This requires, in turn, an initial screening of available techniques to determine those that have the potential for monitoring the analyte. We begin by considering a useful way to classify analytical techniques. 

Gardone, M. J. Detection and Determination of Error in Analytical Methodology. Part 11. Gorrection for Gorrigible Systematic Error in the Gourse of Real Sample Analysis, /. Assoc. Off. Anal. Chem. 1983, 66, 1283-1294. 

Caustic soda solutions are normally tested for general alkalinity and percentages of NaCl, Na2S04, and NaClO as weU as for Fe and Ni levels. The general methods are outlined in Table 22. Detailed analytical methodologies are available from the major caustic soda suppHers. 

T. Cairns and J. Sherma, eds.. Comprehensive Analytical Profiles of Important Pesticides, CRC Press, Boca Raton, Fla., 1992, 304 pp. From the series ModemMethods for Pesticide Analysis, provides detailed information on properties and analytical methodology for nine prominent pesticides, pyrethroids, and fumigants in food. Includes formulations and uses, chemical and physical properties, toxicity data, and tolerances on various foods and feeds. Analytical information may be given in enough detail for methods to be carried out without having to consult additional Hterature sources. 

Special purpose articles describe analytical methodology for specialized systems such as art objects, surfaces, or residues (see Fine ART examination AND CONSERVATION NONDESTRUCTIVE TESTING SURFACE AND INTERFACE ANALYSIS and, Trace AND RESIDUE ANALYSIS). Many of the techniques Utilized for these systems ate also discussed ia materials charactetizatioa and separations articles. The methodology and some of the techniques are unique, however, and the emphasis ia these special topics articles is oa appHcatioa to a particular system. 

The unique chemical, physical, and spectroscopic properties of organosiUcon compounds are reflected in the analytical methodology used for the detection, quantification, and characterization of these compounds. Several thorough, up-to-date reviews dealing with analytical methods appHed to siUcones have beenpubhshed (434—436). 

The extent of chemical and physical interactions among the components of a dmg dehvery system are characterized. Changes in chemical composition can be detected by analytical methodologies. The dmg formulation and the occurrence of byproducts need to be identified. Physical changes, such as swelling and delamination, also need to be identified so that corrective actions can be taken. 

Sounds with a boiling point above 100° C). Figure 25-42 presents an lustration of the Method 0010 sampling train. Comprehensive chemical analyses, using a variety of applicable analytical methodologies, are conducted to determine the identity and concentration or the organic materials. 

Draw up a list of all analytical methodologies that are in principle capable of satisfying this condition. 

What part of the total variance is due to the analytical methodology, and how much is due to variations in the product ... 

Analytical methodologies need to be further developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances. 

In the past, no snitable analytical methodologies were capable of investigating these multiple reactions and even today, the complete extraction and analysis of all the componnds is still a difficult task. The methods for extraction must be optimized for each sample according to the solubility of either phytylated (chlorophylls and pheophytins) or dephytylated (chlorophyllides and pheophorbides) derivatives, often requiring several repeated steps and the use of a single or a mixture of organic solvents. 

Evaluates recent advances in analytical methodology for detecting both natural and synthetic colorants, their quality, quantity, and degradation during processing and storage... 

There is a discrepancy between the cyanide criteria for both aquatic and drinking water standards and the current analytical technology. The criteria are stated for free cyanide (which Includes hydrocyanic acid and the cyanide ion), but the EPA approved analytical methodology for total cyanide measures the free and combined forms (11). This test probably overestimates the potential toxicity. An alternative method (cyanides amenable to chlorination) measures those cyanide complexes which are readily dissociated, but does not measure the iron cyanide complexes which dissociate in sunlight. This method probably tends to underestimate the potential toxicity. Other methods have been proposed, but similar problems exist (12). The Department of Ecology used the EPA-approved APHA procedure which includes a distillation step for the quantification of total cyanide (13,14). A modification of the procedure which omits the distillation step was used for estimation of free cyanide. Later in the study, the Company used a microdiffusion method for free cyanide (15). 

A review is presented here of certification approaches, followed by several of the major agencies and individual developers of RMs for chemical composition, addressing some of the many associated scientific aspects that significantly impinge on the conduct and outcome of the analytical characterization exercises. These include definition of analytical methods selection of analytical methodologies, analysts and laboratories in-house characterization and cooperative inter-laboratory characterization. 

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