Coupling chromatographic methods, trace analysis

Traditional methodologies for structural identification of trace level impurities in drng substances/products usually involve fractionation of each impurities using a scaled-np analytical chromatographic method, followed by off-line spectroscopic analysis. Coupling of HPLC separation and electrospray mass spectrometry allows on-line acquisition of full scan mass spectra and generation of tandem mass spectrometric data. LC/ESI MS has revolntionized trace analysis for qnalitative and quantitative studies in pharmaceutical analysis. 

Fundamentally, trace analysis is possible with a range of different procedures. In the organic pollutant determination, chromatographic methods such as GC, GC-MS, HPLC and, more recently immunoassay and to a greater degree, the coupling of HPLC with electrochemical detection (HPLC-EC) (see below) take precedence (cf. )... 

As an alternative to conductivity detection, Diemer and Heumann [74], Seu-bert et al. [75-78], and Pergantis et al. [79] successfully employed inductively coupled plasma mass spectrometry (ICP-MS) as an elegant but costly detection method for trace bromate analysis. By adapting the chromatographic conditions to the requirements and possibilities of ICP-MS, minimum detection limits below lOOng/L can be achieved [75,76]. The most important changes include the increase of the anion-exchange capacity of the separator column and the... 

Apart from innovations such as coupling spectrophotometric detection (Parker et al, Parker and Hudson ) or titrimetry (Parker et al ) at the outlet end of the gas chromatographic column, conventional thermal conductivity or flame ionization methods of gas chromatographic analysis are not effective in the chromatography of the trace tetraalkyl leads due to the extreme complexity of the gasoline base stock. 

Multidimensional separation techniques have been developed with a number of objectives such as increased perik capacity and/or Improved resolution for the separation of highly complex samples, shortened analysis time via heartcut and partial analysis of fractions from complex samples, and enhanced detection of trace components. Both GC-GC, LC-GC, and LC-LC methods as well as various other multidimensional combinations involving CZE or SEC have been described and coupled to mass spectrometry. In most cases, the multidimensional approach comprises a combination of two chromatographic columns, either containing two different stationary phases (both GC and LC), or developed with two different mobile phases (LC only). The sample is injected onto the first column. Part of the chromatogram is heart-... 

Plasma source mass spectrometry is a powerful analytical technique for trace element analysis with species selectivity when coupled with a suitable chromatographic sample introduction method. It combines the ability of the analytical plasma to atomize and ionize samples efficiently, with the sensitivity and selectivity of mass spectrometry. Following the commercial introduction of inductively coupled plasma mass spectrometry (ICP-MS) instrumentation in 1983, interest in plasma source MS increased rapidly. The enormous popularity of ICP-MS is not surprising considering the low levels of detection possible for a wide range of elements. In addition, multielement capability and the availability of isotope ratio information help make plasma source MS particularly... 

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