Analytical method performance

QC tests are carried out according to validated analytical methods or established methods from pharmacopoeias US Pharmacopoeia and British Pharmacopoeia. Exhibit 10.2 lists some of the QC analytical methods performed on drug intermediates and products. 

Based on expected sample matrix variability, analytical method performance criteria, and budgetary considerations, the gray region is specified at 20 percent of the action level and ranges from 0.8 to l.Ogg/kg. 

In a modern laboratory, automated computer software for data acquisition and processing performs most of data reduction. Raw data for organic compound and trace element analyses comprise standardized calibration and quantitation reports from various instruments, mass spectra, and chromatograms. Laboratory data reduction for these instrumental analytical methods is computerized. Contrary to instrumental analyses, most general chemistry analyses and sample preparation methods are not sufficiently automated, and their data are recorded and reduced manually in laboratory notebooks and bench sheets. The SOP for every analytical method performed by the laboratory should contain a section that details calculations used in the method s data reduction. 

Some processing of samples before the determination of the analytes is often required to achieve optimum analytical method performance. Sample processing also defines exactly... 

The column is arguably the most important component in HPLC separations. The availability of a stable, high-performance column is essential for developing a rugged, reproducible analytical method. Performance of columns from different vendors can vary widely. Separation selectivity, resolution, and efficiency depend on the type and quality of the column. Proper column maintenance is the key to ensure optimum column performance as well as an extended column lifetime. It ensures stability of column plate number, band symmetry, retention, and resolution. The major issues related to column performance and maintenance are discussed here. 

Validation may be viewed as the documentation of evidence that a system does what it purports to do. Thus, analytical method validation is the maintenance of documentation in experimental databases to verify that an analytical method performs in the manner intended. The validation report should include the following. 

Table 6.5. Summary of Analytical Method Performance Parameters for Vitamin Analysis...

Method Performance Detection Limits One common way of assessing one aspect of method performance is by detection limit, or by the term detectivity (power to detect the analyte), as opposed to the term sensitivity (strictly the slope of the calibration function), as used in the past by this author (Ihnat 1984). The concept of detection limit is defined and discussed in books on analytical chemistry and in papers by analysts and committees delving into the mathematical, statistical and quality facets of analytical method performance. Basically it is the amount, absolute (mass) or relative (mass/volume or mass/mass,... 

The procedure must provide adequate detail so that a designated laboratory can reproduce the method without deviation. The validation report includes the experimental design and the data that justify the conclusion that the analytical method performs as intended. Minimum acceptable performance criteria must also be defined in the report. 

Valcarcel, M. Tuque de Castro, M. D. A Hierarchical Approach to Analytical Chemistry, Trends Anal. Chem., 1995,14, 242-250. Further details on evaluating analytical methods may be found in Wilson, A. L. The Performance-Characteristics of Analytical Methods, Part l-Talanta, 1970, 17, 21-29 Part ll-Talanta, 1970, 17, 31M4 Part lll-Talanta, 1973, 20, 725-732 Part IV-Talanta, 1974,21, 1109-1121. 

A final component of a quality control program is the certification of an analyst s competence to perform the analysis for which he or she is responsible. Before an analyst is allowed to perform a new analytical method, he or she may be required to successfully analyze an independent check sample with acceptable accuracy and precision. The check sample should be similar in composition to samples that the analyst will routinely encounter, with a concentration that is 5 to 50 times that of the method s detection limit. 

Automated analyzers may be used for continuous monitoring of ambient poUutants and EPA has developed continuous procedures (23) as alternatives to the referenced methods. Eor source sampling, EPA has specified extractive sampling trains and analytical methods for poUutants such as SO2 and SO [7446-11-9] sulfuric acid [7664-93-9] mists, NO, mercury [7439-97-6], beryUium [7440-41-7], vinyl chloride, and VOCs (volatile organic compounds). Some EPA New Source Performance Standards requite continuous monitors on specified sources. 

High Performance Liquid Chromatography (hpic). Hplc is currently the fastest growing analytical method and is now available in many laboratories. DL-Analysis by hplc has already been described and hplc methods have been reviewed (122). 

There are a variety of analytical methods commonly used for the characterization of neat soap and bar soaps. Many of these methods have been pubUshed as official methods by the American Oil Chemists Society (29). Additionally, many analysts choose United States Pharmacopoeia (USP), British Pharmacopoeia (BP), or Pood Chemical Codex (FCC) methods. These methods tend to be colorimetric, potentiometric, or titrametric procedures. However, a variety of instmmental techniques are also frequendy utilized, eg, gas chromatography, high performance Hquid chromatography, nuclear magnetic resonance spectroscopy, infrared spectroscopy, and mass spectrometry. 

Mixtures can be identified with the help of computer software that subtracts the spectra of pure compounds from that of the sample. For complex mixtures, fractionation may be needed as part of the analysis. Commercial instmments are available that combine ftir, as a detector, with a separation technique such as gas chromatography (gc), high performance Hquid chromatography (hplc), or supercritical fluid chromatography (96,97). Instmments such as gc/ftir are often termed hyphenated instmments (98). Pyrolyzer (99) and thermogravimetric analysis (tga) instmmentation can also be combined with ftir for monitoring pyrolysis and oxidation processes (100) (see Analytical methods, hyphenated instruments). 

In a general way, the identification of asbestos fibers can be performed through morphological examination, together with specific analytical methods to obtain the mineral composition and/or stmcture. Morphological characterization in itself usually does not constitute a reHable identification criteria (1). Hence, microscopic examination methods and other analytical approaches are usually combined. 

The analysis was performed by XRF method with SR. SRXRF is an instrumental, multielemental, non-destructive analytical method using synchrotron radiation as primary excitation source. The fluorescence radiation was measured on the XRF beam-line of VEPP-3 (E=2 GeV, 1=100 mA), Institute of Nuclear Physics, Novosibirsk, Russia. For quality control were used international reference standards. 

Performance Specifications for Automated Analytical Methods for Measuring Carbon Monoxide... 

An easy to use nomograph has been developed for the solubility of liquid hydrocarbons in water at ambient conditions (25°C). The accuracy of the nomograph has been checked against available solubility data. Performance of the nomograph has been compared with the predictions given by two available analytical correlations. The nomograph is much simpler to use and far more accurate than either of the analytical methods. 

As with any analytical method, the ability to extract semiquantitative or quantitative information is the ultimate challenge. Generally, static SIMS is not used in this mode, but one application where static SIMS has been used successfully to provide quantitative data is in the accurate determination of the coverage of fluropolymer lubricants. These compounds provide the lubrication for Winchester-type hard disks and are direaly related to ultimate performance. If the lubricant is either too thick or too thin, catastrophic head crashes can occur. 

Because of the complex nature of the discharge conditions, GD-OES is a comparative analytical method and standard reference materials must be used to establish a unique relationship between the measured line intensities and the elemental concentration. In quantitative bulk analysis, which has been developed to very high standards, calibration is performed with a set of calibration samples of composition similar to the unknown samples. Normally, a major element is used as reference and the internal standard method is applied. This approach is not generally applicable in depth-profile analysis, because the different layers encountered in a depth profile of ten comprise widely different types of material which means that a common reference element is not available. 

The broad pore size distribution of Sepharose makes it well apt for the analysis of broad molecular mass distributions of large molecules. One example is given by the method for determination of MWD of clinical dextran suggested in the Nordic Pharmacopea (Nilsson and Nilsson, 1974). Because Superose 6 has the same type of pore size distributions as Sepharose 6, many analytical applications performed earlier on Sepharose have been transformed to Superose in order to decrease analysis time. However, Sepharose is suitable as a first try out when no information about the composition of the sample, in terms of size, is available. 

Electrospray ionization mass spectrometry (ESI-MS) is an analytical method for mass determination of ionized molecules. It is a commonly used method for soft ionization of peptides and proteins in quadmpole, ion-trap, or time-of-flight mass spectrometers. The ionization is performed by application of a high voltage to a stream of liquid emitted from a capillaty. The highly charged droplets are shrunk and the resulting peptide or protein ions are sampled and separated by the mass spectrometer. 

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