Sample type trace mixture

Liquid chromatography/mass spectrometry (LC/MS)-based techniques provide unique capabilities for pharmaceutical analysis. LC/MS methods are applicable to a wide range of compounds of pharmaceutical interest, and they feature powerful analytical figures of merit (sensitivity, selectivity, speed of analysis, and cost-effectiveness). These analytical features have continually improved, resulting in easier-to-use and more reliable instruments. These developments coincided with the pharmaceutical industry s focus on describing the collective properties of novel compounds in a rapid, precise, and quantitative way. As a result, the predominant pharmaceutical sample type shifted from nontrace/pure samples to trace mixtures (i.e., protein digests, natural products, automated synthesis, bile, plasma, urine). The results of these developments have been sig-... 

Figure 1.1 Structure analysis matrix that illustrates pharmaceutical analysis preferences for four specific sample types nontrace/pure nontrace/ mixture trace/pure and trace/mixture. (Courtesy of Milestone Development Services, Newtown, Pa., USA.)...

The evolution of mass spectrometry has been both dramatic and fascinating. Trace analytical measurement, specifically the demand for trace mixture analysis, has created an increased demand for this powerful tool. In many cases, the preference for the trace mixture sample type has transformed the mass spectrometer into a gold standard platform for qualitative and quantitative assays. 

LC-GC is a very powerful analytical technique because of its selectivity and sensitivity in analysing complex mixtures and therefore it has been used extensively to determine trace components in environmental samples (2, 5,77). LC allows preseparation and concentration of the components into compound types, with GC being used to analyse the fractions. The advantages of on-line LC-GC over the off-line System are, first, the less sample which is required and, secondly, that there is less need for laborious sample pretreatment because the method is automated (78). 

Mass spectrometry can be specific in certain cases, and would even allow on-line QA in the isotope dilution mode. MS of molecular ions is seldom used in speciation analysis. API-MS allows compound-specific information to be obtained. APCI-MS offers the unique possibility of having an element- and compound-specific detector. A drawback is the limited sensitivity of APCI-MS in the element-specific detection mode. This can be overcome by use of on-line sample enrichment, e.g. SPE-HPLC-MS. The capabilities of ESI-MS for metal speciation have been critically assessed [546], Use of ESI-MS in metal speciation is growing. Houk [547] has emphasised that neither ICP-MS (elemental information) nor ESI-MS (molecular information) alone are adequate for identification of unknown elemental species at trace levels in complex mixtures. Consequently, a plea was made for simultaneous use of these two types of ion source on the same liquid chromatographic effluent. 

Chemical and biological analyses of trace organic mixtures in aqueous environmental samples typically require that some type of isolation-concentration method be used prior to testing these residues the inclusion of bioassay in a testing scheme often dictates that large sample volumes (20-500 L) be processed. Discrete chemical analysis only requires demonstration that the isolation technique yields the desired compounds with known precision. However, chemical and/or toxicological characterization of the chemical continuum of molecular properties represented by the unknown mixtures of organics in environmental samples adds an extra dimension of the ideal isolation technique ... 

The electrical signal from a detector is amplified and fed into a recorder or computer for analysis. A typical recorder trace is shown in Figure 3.5. Each peak represents a component in the original mixture. A peak is identified by a retention time, the time lapse between injection of the sample and the maximum signal from the recorder. This number is a constant for a particular compound under specified conditions of the carrier gas flow rate temperature of the injector, column, and detector and type of column. Retention time in GC analysis is analogous to the R value in thin-layer or paper chromatography. 

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