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a robust analytical tool, applicable in almost all analytical situations. This
was caused by the introduction of atmospheric pressure ionization (API)
sources. The advent of API/LC/MS converted all earlier LC/MS interfaces
like thermospray and particle beam ionization of fast atom bombardment
to obsolete techniques.
The statement of Krull and Cohen may illustrate the dimension of
this change:
There are at least two fundamental views on the future role of MS
in biotechnology HPLC. Is the mass spectrometer an expensive
sophisticated LC detector? Or, is the chromatograph an expensive
sample-preparation device for a mass spectrometer? One of the
newer developments in LC/MS is that this distinction will cease
to be important in the future. 1
The change of the status of LC/MS from hyphenated method to routine
analytical tool attracted a new generation of users, who are taking the
hyphenation for granted and treat a LC/MS instrument as a single unit.
Similar evolution was observed for GC/MS in the past. Technical and
methodical progress in LC/MS in the last few years was reviewed in several
books and publications. Special reviews were devoted to application of
2–4
LC/MS in forensic toxicology. 5–9
2.2 Methodical Considerations Relevant to
Forensic Analysis
Recent years have seen some publications on the general aspects of LC/MS
that are of relevance for forensic toxicological analysis. These studies con-
cerned the quality of the sample and its influence on the chromatographic
signal, optimization of chromatographic analysis, application of various ion-
ization sources, and various mass analyzers in toxicology.
2.2.1 Separation Issues
2.2.1.1 Sample Pretreatment Methods and Matrix Suppression
It is common knowledge that poor sample preparation procedure may ruin
any detection, even under the application of most modern and sophisticated
techniques. This is valid also for LC/MS. It should be noted that in the earlier
phase of application some authors tried to apply LC/MS/MS in a flow-
injection mode, i.e., the extracts of serum or urine were directly injected into
API/MS without chromatographic separation. This procedure was checked
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