ABSTRACT

Mass spectrometry (MS) has become one of the most important analytical tools employed in the analysis of pharmaceuticals. This can most likely be attributed to the availability of new instrumentation and ionization techniques that can be used to help solve difficult bioanalytical problems associated with this field (18). Perhaps the best illustration of this occurrence is the development of electrospray (ESI) and related atmospheric-pressure ionization (API) techniques, ionspray (nebulizer-assisted API), turbo ionspray (thermally assisted API), and atmospheric pressure chemical ionization (APCI; nebulization coupled with corona discharge), for use in drug disposition studies. The terms ESI and ionspray tend to be used interchangeably in the literature. For the purpose of this review, the term API will be used to describe both ESI and ionspray. In recent years there has been an unprecedented explosion in the use of instrumentation dedicated to API/MS (4,6,8-14). API-based ionization techniques have now become the method of choice for the analysis of pharmaceuticals and their metabolites. This has made thermospray (TSP), the predominant LC/MS technique during the 1980s, obsolete (15). Numerous reports describing the utility of API/MS for pharmaceutical analysis have appeared in the literature over the last decade (7). The

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increased sensitivity that can be attained with API-based methodology, together with the availability of robust instrumentation, has resulted in TSP being phased out as a practical technique in pharmaceutical analysis. Thus, methodology based on TSP ionization will not be discussed in detail in this review. The pharmaceutical industry has certainly been at the forefront of implementing API/MS, and this, perhaps, reflects the utility of this technique for the analysis of pharmaceuticals. Several reviews have appeared recently concerning the use of MS in drug disposition and pharmacokinetics (6,16-18).