Derivatization in Sample Preparation for LC‐MS Bioanalysis

LC–MS based bioanalysis has recently progressed to become the method of choice for analyzing various types of compounds in complex matrices. However, the analysis can be challenging due to various factors, including inherent low concentrations in biological samples, undesirable ionization efficiency or chromatographic behavior, and instability in complex matrices. Chemical derivatization could be a valuable means to improve chromatographic behaviors, MS detection, and lability of the molecule of interest. By introducing exogenous functional groups via chemical derivatization, unfavorable physicochemical properties for LC-MS bioanalysis of the analytes will be improved to strengthen the LC–MS performance. Although the development and optimization of chemical derivatization employed bioanalysis may be time-consuming, it has been acknowledged as an indispensable technique to extend the application of LC–MS analysis to a wider range of analytes. The past decades has witnessed numerous successful applications of derivatization integrated LC–MS bioanalysis for multiple compounds such as drug metabolites, proteins, biomarkers, residues and toxins in various matrices. This chapter introduced the derivatization strategies in sample preparation for quantitative LC–MS bioanalysis, and provided applications highlighting the impact of chemical derivatization to enhance the LC–MS performance.