The Analytical Laboratory

Analysis by its very nature requires the repetition of standardised techniques and is an ideal area for automation. Automation in the analytical laboratory comprises four groups of activities. 

Instrument automation. Designed to speed up the tasks of sample preparation and analysis. 

Communications. The means by which information is passed from equipment on the laboratory bench to the analyst and then on to the user/decision maker. 

Data to information conversion. Converts the data from analytical instruments into useful information. 

Information Management. Stores the data as it is generated to be used for onward delivery of information and hence the creation of knowledge in the user. 

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This does not have to be so Why not build an uninterrupted stream of information from the producer (the bench chemist) to the consumer (the reader of a journal or book, or the scientist that puts a query into a database) It is quite clear that the producers of information knows best what experiments were done, what observations were made, what results have been obtained. They should put this information into electronic laboratory books, augmented with spectral data (that they can obtain directly from the analytical laboratory). From this electronic repository aU other information sources -manuscripts, journals, books, databases - could be filled, clearly sometimes by manual selection, but not by changing data ... 

The following exercises and experiments help connect the material in this chapter to the analytical laboratory. 

The use of "fixed" automation, automation designed to perform a specific task, is already widespread ia the analytical laboratory as exemplified by autosamplers and microprocessors for sample processiag and instmment control (see also Automated instrumentation) (1). The laboratory robot origiaated ia devices coastmcted to perform specific and generally repetitive mechanical tasks ia the laboratory. Examples of automatioa employing robotics iaclude automatic titrators, sample preparatioa devices, and autoanalyzers. These devices have a place within the quality control (qv) laboratory, because they can be optimized for a specific repetitive task. AppHcation of fixed automation within the analytical research function, however, is limited. These devices can only perform the specific tasks for which they were designed (2). 

All these microanalytical methods are in the everyday use at the analytical laboratory of INEOS RAS. 

Ultrafiltration utilizes membrane filters with small pore sizes ranging from O.OlS t to in order to collect small particles, to separate small particle sizes, or to obtain particle-free solutions for a variety of applications. Membrane filters are characterized by a smallness and uniformity of pore size difficult to achieve with cellulosic filters. They are further characterized by thinness, strength, flexibility, low absorption and adsorption, and a flat surface texture. These properties are useful for a variety of analytical procedures. In the analytical laboratory, ultrafiltration is especially useful for gravimetric analysis, optical microscopy, and X-ray fluorescence studies. 

Electrodriven separation techniques are destined to be included in many future multidimensional systems, as CE is increasingly accepted in the analytical laboratory. The combination of LC and CE should become easier as vendors work towards providing enhanced microscale pumps, injectors, and detectors (18). Detection is often a problem in capillary techniques due to the short path length that is inherent in the capillary. The work by Jorgenson s group mainly involved fluorescence detection to overcome this limit in the sensitivity of detection, although UV-VIS would be less restrictive in the types of analytes detected. Increasingly sensitive detectors of many types will make the use of all kinds of capillary electrophoretic techniques more popular. 

Many modern instruments used in the analytical laboratory are interfaced with a computer and a printer provides a permanent record of the experimental data and the final result may even be given. This printout should be permanently attached to the observations page of the laboratory record book, and it should be regarded as normal practice to perform a rough calculation to confirm that the printed result is of the right order. 

Various methods of heating are required in the analytical laboratory ranging from gas burners, electric hot plates and ovens to muffle furnaces. 

Hot plates. The electrically heated hot plate, preferably provided with three controls — Low , Medium and High — is of great value in the analytical laboratory. The heating elements and the internal wiring should be totally enclosed this protects them from fumes or spilled liquids. Electric hot plates with stepless controls are also marketed these permit a much greater selection of surface temperatures to be made. A combined electric hot plate and magnetic stirrer is also available. For some purposes a steam bath may be used. 

The two examples of sample preparation for the analysis of trace material in liquid matrixes are typical of those met in the analytical laboratory. They are dealt with in two quite different ways one uses the now well established cartridge extraction technique which is the most common the other uses a unique type of stationary phase which separates simultaneously on two different principles. Firstly, due to its design it can exclude large molecules from the interacting surface secondly, small molecules that can penetrate to the retentive surface can be separated by dispersive interactions. The two examples given will be the determination of trimethoprim in blood serum and the determination of herbicides in pond water. 

Prichard, E. (Co-ordinating Author), Quality in the Analytical Laboratory, ACOL Series, Wiley, Chichester, UK, 1995. 

Research use of analytical results in the framework of a nonanalytical setting, such as a governmental investigation into the spread of pollution here, a strict protocol might exist for the collection of samples (number, locations, time, etc.) and the interpretation of results, as provided by various consultants (biologists, regulators, lawyers, statisticians, etc.) the analytical laboratory would only play the role of a black box that transforms chemistry into numbers in the perspective of the laboratory worker, calibration, validation, quality control, and interpolation are the foremost problems. Once the reliability and plausibility of the numbers is established, the statisticians take over. 

Of all the requirements that have to be fulfilled by a manufacturer, starting with responsibilities and reporting relationships, warehousing practices, service contract policies, airhandUng equipment, etc., only a few of those will be touched upon here that directly relate to the analytical laboratory. Key phrases are underlined or are in italics Acceptance Criteria, Accuracy, Baseline, Calibration, Concentration range. Control samples. Data Clean-Up, Deviation, Error propagation. Error recovery. Interference, Linearity, Noise, Numerical artifact. Precision, Recovery, Reliability, Repeatability, Reproducibility, Ruggedness, Selectivity, Specifications, System Suitability, Validation. 

Initial Situation An experimental granulation technique is to be evaluated a sample of tablets of the hrst trial run is sent to the analytical laboratory for the standard batch analysis prescribed for this kind of product, including content uniformity (homogeneity of the drug substance on a tablet-to-tablet basis, see USP Section (905)" ), tablet dissolution, friability (abrassion resistance), hardness, and weight. The last two tests require little time and were therefore done first. (Note Hardness data is either given in [kg-force] or [N], with 1 kg = 9.81 Newton). 

Pressures Helium—60 psig, Hydrogen—10 psig Quantitative determinations of purity were made at the Analytical Laboratory of Dow Chemical Co. by GLC using flame ionization and electron capture detectors. Unknown samples were compared with prepared standards containing the compounds in question. 

A protocol must be established and followed for sample preparation, labeling, packaging, shipping, and chain-of-custody procedures. Also, the volume of the samples will be specified by the analytical laboratory depending on the analytical methods to be used and the desired sensitivity. Accordingly, principal attention will be given here to the sampling methods, preparation of the samples for analysis, and QA/QC aspects of both. 

Pesticides used on crops grown on the test site in previous seasons may also have an impact on the outcome of a field residue trial. Carryover of prior pesticide applications could contaminate samples in a new trial, complicate the growth of the crop in a trial, or cause interference with procedures in the analytical laboratory. For this reason, an accurate history of what has transpired at the potential test site must be obtained before the trial is actually installed. The protocol should identify any chemicals of concern. If questions arise when the history is obtained, they should be reviewed with the Study Director prior to proceeding with the test site. In most annual crop trials, this will not be a significant issue owing to crop rotations in the normal production practices, because the use of short residual pesticides and different chemical classes is often required for each respective crop in the rotation. However, in many perennial crops (tree, vines, alfalfa, etc.) and monoculture row crops (cotton, sugarcane, etc.), the crop pesticide history will play a significant role in trial site selection. 

For stone fmit, e.g., olive cherries, where the mature fruit is analyzed, the stone should be removed, and the weight of pulp and stone should be recorded. The residue is calculated on the basis of whole fruit. This step can be done either in the field prior to the fruit being frozen, which makes the procedure easier, or in the analytical laboratory. In either case, care needs to be taken to avoid cross-contamination. 

Often where direct data capture systems are employed in the analytical laboratory, an additional bar code or sequential labelling system may be incorporated and could be added to this system to ensure complete union with the analytical laboratory receiving the samples. 

Transport of samples to the analytical laboratory presents the staff of organizations conducting field frials with the most difficult problem and is the area where many studies have failed as a result of samples being lost, defrosted, or shipped to the wrong place. The number of experiences and ill fortune that have befallen many Field Trial Managers are too many to mention. 

There are generally two ways to ship samples to the analytical laboratory within Europe. The first method involves shipping frozen samples in the presence of dry ice. These samples are generally shipped by airfreight to the analytical laboratory. The second method is to ship by frozen transport via the road. The two methods of shipment both have some advantages and disadvantages. Table 1 highlights the two scenarios. 

Table 1 Advantages and disadvantages between two methods of shipping samples to the analytical laboratory within Europe...

At a minimum, the processing phase must identify the RAC to be processed and the processed fractions to be produced. Other essential information is the quantity of the RAC to be delivered to the processor and an indication of the quantity of the processed fractions to be produced. The minimum quantity of each processed fraction is driven by the requirement of the analytical laboratory and in most cases includes a substantial excess allowance. The minimum quantity of RAC to be processed may be driven by the amount of processed commodity to be produced or the minimum raw material requirements of some processes or equipment to be used. Another factor to be considered in establishing minimum amounts of both RAC and processed fractions is the amount required for a representative sample. An amount of 10 lb of strawberries may provide a representative sample of an experimental plot, whereas the same amount of pumpkins almost certainly would not. 

Specific information on the handling of the processed fractions may also be included. Specific containers or types of containers may be required to minimize analytical interference. Sample identification numbers may be assigned in the protocol or may be generated by the processing facility. In either case, each processed fraction should have a unique identification number to reduce confusion at the processing facility and at the analytical laboratory where the residues will be determined. 

Once the target number of samples was defined, the frequency of collection and the number of samples to be collected on each collection date were determined, based on an overall total sampling period of 1 year. The sampling plan specified collection every other week, primarily to accommodate the workload at the analytical laboratories. Sampling had to occur early in the week to preclude problems with shipping samples over the weekend. With these considerations in place, specific dates for collection of commodity samples could readily be set. 

Upon receipt at the analytical laboratory, the receiving department should immediately examine the integrity of the samples. If a sample is damaged, or its integrity is in any way questionable, or it does not meet the protocol definition (e.g., leaf rather than head lettuce), then a re-shop should be ordered (i.e., the shopper is required... 

The locked cells in any worksheet could not be opened or altered by laboratory staff without the knowledge and agreement of the Study Director. Use of the locking function in the workbook, therefore, constrained the analytical laboratories to a single system for recording data and calculating results. 

In any study involving analyses, part of the responsibility of management at the analytical laboratory is the review and approval of intermediate and final reported results. In an LSMBS, such review and approval must take place at each analytical laboratory involved in the study. However, different laboratories may focus on different aspects of the analyses, and some means to ensure that review procedures and approaches are consistent among the laboratories is needed. It is advisable, therefore, to include an additional review, termed here an external review , beyond that conducted by the individual laboratories. 

QA is an important aspect of any technical study. It is particularly crucial in an LSMBS, because several hundred participants, widely separated geographically, are involved. The analytical laboratories typically have standard provisions for QA inspections and reviews, and the field phase management organization is also likely to have standard provisions for QA inspection and review. Shoppers, however, are typically external to study management and analytical laboratories and, thus, are not directly covered by existing QA systems. The study design must include a means by which the field phase, i.e., sample collection and shipment by the shoppers, is made to comply with QA requirements. 

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