21] Measuring DNA adducts by gas chromatography-electron capture-mass spectrometry: Trace organic analysis

Abstract

This chapter discusses the practical experience in method development for the determination of trace amounts of DNA adducts, by gas chromatography-electron capture-mass spectrometry (GC-EC-MS). It has detected femtomole amounts of such analytes, by optimizing sample preparation (involving extraction, chemical reaction, and purification steps, starting with a biological sample) and low-attomole amounts of pure, derivatized standards, by GC-EC-MS. Although such methodology is already useful, the concepts and techniques described extend the sample preparation to the attomole level. In this chapter, the work on chemical transformation is emphasized as a part of sample preparation. This is a means to broaden the range of compounds that can be detected by GC-EC-MS. Also, the experience, in operating a GC-EC-MS to achieve attomole detection limits routinely (for standards), is discussed in the chapter. New ionization techniques for MS, such as electrospray and matrix-assisted laser desorption, are increasing the ability of MS to analyze “nonvolatile” substances present even in aqueous samples. Less new but of continuing importance, as a desorption/ionization technique, in this respect is fast atom bombardment, In contrast, this chapter discusses the procedures, in which significant chemical treatment of the sample precedes the “old technique” of GC, to deliver the analyte into the MS. The desorption approaches are attractive, because they can minimize sample preparation. They are also unique in their ability to achieve the direct detection of medium to high molecular weight biopolymers by MS.