LC-MS development strategies for quantitative bioanalysis

Although quantitative bioanalysis using liquid chromatography in conjunction with atmospheric pressure ionization tandem mass spectrometry (LC-MS/MS) has been in use for approximately fifteen years, new concepts and technologies are continuously being introduced to enhance the multiple steps of quantitative LC-MS/MS bioanalysis. In this review article, we have focused on concepts and technologies that have recently been introduced to achieve further improvements in biological sample collection/storage and extraction, chromatography and mass spectrometric detection. Under these major headings, a number of specific topics are presented, summarizing the most recent findings in these areas. Included among the topics discussed are: off-line plasma extraction, on-line plasma extraction, enhanced mass resolution, atmospheric pressure photo ionization, high-field asymmetric waveform ion mobility spectrometry, electron capture atmospheric pressure chemical ionization, enhancing MS detection via formation of anionic and cationic adducts, chemical derivatization, ultra-performance chromatography, hydrophilic interaction chromatography, and MS-friendly ion-pair reversed-phase chromatography. In the end, we discuss potential pitfalls in LC-MS/MS bioanalysis and the means to avoid them. Such pitfalls may occur due to mass spectral interference from metabolites or prodrugs, due to the use of inappropriate calibration standard and quality control samples for analysis involving unstable drugs or metabolites, and due to the wild card phenomenon commonly known as the matrix effect.