In the pharmaceutical industry, liquid chromatography–tandem mass spectrometry (LC–MS-MS) is already an established method for quality control and quantification of drugs in different matrices. Additionally, this hyphenated analytical tool is becoming more and more important in clinical chemical analysis (that is, in therapeutic drug monitoring).
LC–MS-MS is a very powerful analytical technique because it combines the separation power of LC with the sensitivity and selectivity of MS. However, LC–MS-MS possesses two major drawbacks when analyzing drugs in biological fluids. The first, associated with the mass spectrometer, is that the electrospray source is very susceptible to matrix-related ion-suppression effects. The second drawback concerns the LC. Because of irreversible adsorption and precipitation effects caused by high molecular weight sample components (for example, proteins) complex biofluids cannot be injected and analyzed directly.
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