Laboratory Instrumental Configurations

Fig. 3.12. Non-invasive Raman spectra of pharmaceutical capsules. The spectra were obtained using a laboratory instrument configured in the transmission Raman geometry and a standard commercial Raman microscope (Renishaw) in conventional backscattering geometry. The Raman spectra of an empty capsule shell (lowest trace) and the capsule content itself (top trace, the capsule content was transferred into an optical cell) are shown for comparison. The dashed lines indicate the principal Raman bands of the capsule and of the API (this figure was published in [65], Copyright Elsevier (2008))...

Different capillary columns are available for organic acid separation and analysis. In our laboratory, the gas chromatography column in all GC-MS applications is crosslinked 5% phenyl (poly)methyl silicone, 25 m internal diameter 0.20 mm stationary phase film thickness 0.33 pm (Agilent HP-5, DB-5, or equivalent). Several instrument configurations are commercially available, which allow for positive identification of compounds by their mass spectra obtained in the electron impact ionization mode. A commercially available bench-top GC-MS system with autosampler (Agilent 6890/5973, or equivalent) is suitable. Software for data analysis is available and recommended. The use of a computer library of mass spectra for comparison and visualization of the printed spectra is required for definitive identification and interpretation of each patient specimen. 

The complications just described can be minimized if there is greater selectivity in the ionization process, as is sometime possible when photoionization is used as the excitation mechanism. Because the ionization energy can be more precisely controlled, it is possible in selected cases to produce only the desired reactant-ion species, or at least to minimize production of other ions. As already noted in the earlier section on formation of excited ions, it is also possible to populate specific internal-energy states of some reactant ions by using a photoionization source. One of the earliest photoionization mass spectrometers used to study interaction of internally excited ions with neutrals was that constructed by Chupka et al.91 Such apparatuses typically incorporate a photon source (either a line or a continuum source) and an optical monochromator, which are coupled to the reaction chamber. Various types of mass analyzer, including sector type, time-of-flight (TOF), and quadrupole mass filters, have been used with these apparatuses. Chupka has described the basic instrumental configuration in some detail.854 Photoionization mass spectrometers employed to study interactions of excited ions with neutral species have also been constructed in several other laboratories.80,1144,142,143 The apparatus recently developed by LeBreton et al.80 is illustrated schematically in Fig. 7 and is typical of such instrumentation. 

The following schematic diagrams show typical plug and outlet configurations used on common laboratory instruments and devices.1 These figures will assist in identifying which circuits and capacities will be needed to operate different pieces of equipment. 

Lacking assay accuracy may also stem from the fact, that most LC-MS/MS methods used in clinical laboratories are still locally designed laboratory-developed tests operating on very heterogeneous instrument configurations. Consequently,... 

In one new laboratory the instrument configuration was reproduced as faithfully as possible The instrument was similar but of a different make. 

All of the laboratory instrumental methods have been practically adapted for on-site analytical procedures, from pH measurement to NMR analyses. The instruments are generally less versatile than their laboratory counterparts. Dedicated to particular measurements and suitable for harsh environments or hazardous areas, they must be robust, so their design is different. They are configured for industrial process control. Many of them are process analysers for concentration measurements. A continuous sample is introduced via a diaphragm pump into a small tank. At intervals the sample or calibration standards are pumped into the chemistry stream where they are treated depending of the method of analysis (UV, IR). 

One instrument configuration utilized in this laboratory is shown in Figure 5. In this instrument the column was mounted in a constant temperature gas chromatograph oven, which also served to heat the air circulated through the DFI probe. A zero dead volume union is typically used to connect the column to a short length of 4-8 ym i.d. or contoured (tapered) fused silica restrictor. The restrictor and probe tip are heated to compensate for cooling due to decompression of the fluid during the DFI process. 

A final point of note is that it is advisable to use the simplest analyzer possible for application. In the laboratory marketplace, extra features or extra flexibility in instrument configuration for a Raman spectrometer are perceived as useful even if they are not needed at the time of purchase. These features often prove to be critical when making an instrument selection. The situation is very different for a process analyzer. For a process analyzer, extra features not needed for the application, whether they are hardware or software, can in the end prove to be extra failures in the field. Thus, it is always advisable to use a simple rugged analyzer. 

Before considering the special requirements for automated on-line determination of metals from industrial effluents, it is worthwhile examining the features of standard laboratory procedures associated with the off-line determination of copper as a dithiocarbamate complex by liquid chromatography with electrochemical detection. The off-line determination of copper as its diethyldithiocarbamate complex in aqueous samples, zinc plant electrol3d e, and urine have been described [3, 7, 10] using reverse phase liquid chromatography with amperometric detection. A standard instrumental configuration for the conventional laboratory off-line method as used in these studies is depicted in Fig. 7.2. 

In a GLP-compliant laboratory, a data system must meet explicit requirements guaranteeing the validity, quality, and security of the collected data. Operational qualification (OQ) must be performed after any new devices are installed in the laboratory system and whenever service or repair are performed. The role of OQ is to demonstrate that the instrument functions according to the operational specifications in its current laboratory environment. If environmental conditions are highly variable, OQ should be checked at the extremes in addition to normal ambient conditions. Performance qualification (PQ) must be performed following any new installation and whenever the configuration of the system has been changed. PQ demonstrates that the instrument performs according to the specifications appropriate for its routine use. 

A simple system is comprised of an isocratic pump, a manual injector, a UV detector, and a strip-chart recorder. A schematic diagram of an HPLC instrument is shown in Fig. 15.4. This simple configuration is rarely used in most modern laboratories. A typical HPLC system is likely to consist of a multi-solvent pump, an autosampler, an on-line degasser, a column oven, and a UV/Vis or photodiode array detector all connected to and controlled by a data-handling workstation. Examples of modular and integrated systems are shown in Fig. 15.5. Some of the important instrumental requirements are summarized in Table 15.2. 

There are signs that companies are becoming increasingly aware of the industrial market and some attempts have been made to develop a systematic approach to this problem. Whereas in chnical chemistry the matrix is usually blood or urine, in the industrial area there are many varied matrices. The volume of sales for any matrix is often insufficient to justify the development investment required. An alternative philosophy is needed to meet the requirements economically. The Mettler range of automatic instruments provides one example of a systematic approach to automate a range of analysers. More recently the Zymark Corporation (Zymark Center, Hopkinton, Massachusetts, USA), in the introduction of its Benchmate products, has defined procedures which can be tailored to individual laboratory needs by using essentially similar modules. These modules are coordinated with a simphfled robotic arm. Several tailor-made systems have been developed which have a wide appeal and are easily configurable to particular needs. 

The precise configuration can be chosen according to the laboratory workload. Table 2.2 clearly illustrates the capacities of the various models. These instruments will support a wide range of analytical methods including end-point assays at one or two wavelengths and with one or two steps as well as rate analyses. 

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