Clinical applications of LC-MS

In an editorial in Clinical Chemistry, Kinter [1] questioned why MS is not used more commonly in routine analysis in the clinical laboratory. He indicated that the answer to this question is based on several misconceptions, including the following (a) MS is not amenable to most analytes of interest in chnical assays, (b) MS is too slow and difficult to automate for the sample throughput needed in the clinical laboratory, (c) MS is too expensive, and (d) MS is difficult to operate. Kinter [1] then takes the edge off these arguments. With the material collected in this book, we could do the same. 

In the past few years, LC-MS has rapidly conquered the clinical laboratory, and further developments in this area are expected for the near future. Recent reviews [2-3] highhghted the importance of such developments. Application areas for LC-MS in the clinical laboratory are therapeutic drag monitoring, neonatal screening, reference methods, and toxicology. Today, one should add the rapidly developing area of clinical biomarker discovery to this list [4] (Ch. 18.6). 

In this chapter, we give a taste of the current state-of-the-art of LC-MS in clinical applications. Certainly not all possibilities and applications are discussed in this chapter. Topics discussed are therapeutic drag monitoring (Ch. 12.2) and neonatal screening (Ch. 13.2). In addition, the LC-MS analysis of various classes of drags of abuse, and systematic toxicological analysis are discussed. 

Two other groups [16-17] demonstrated that similar good results could be obtained without the on-line SPE step. Holt et al. [16] performed an off-hne liquid-liquid extraction (LLE) of the basified supernatant with 1-chlorobutane, evaporation to dryness and reconstitution of the sample in LC mobile phase, while Keevil et al. [17] directly injected the supernatant of the protein precipitation step onto the 33x3.0-nun-ID cyano colunm. 

All target compounds are generally analysed in positive-ion ESI-MS, althongh the use of positive-ion atmospheric-pressure chemical ionization (APCI) has been demonstrated as well [15]. Either SIM on the anunoniated [M+NH4] or sodiated molecules [M+Na] is applied, or SRM using the [M+NH4] as precursor ions. For CsA, the [M+NH4] at m/z 1219.8 is fragmented to the protonated molecule [M+H] at m/z 1202.8. For sirolimus and tacrolimus, the losses of 67 Da (NHj, CH3OH, and H2O) or 53 Da (NH3 and 2XH2O) are monitored, respectively. 

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