LC-MS Development Strategies for Quantitative Bioanalysis

Although quantitative bioanalysis using liquid chromatography in conjunction with atmospheric pressure ioni-zation tandem mass spectrometry (LC-MS/MS) has been in use for approximately fifteen years, new concepts and tech-nologies are continuously being introduced to enhance the multiple steps of quantitative LC-MS/MS bioanalysis. In thisreview article, we have focused on concepts and technologies that have recently been introduced to achieve further im-provements 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 ar-eas. Included among the topics discussed are: off-line plasma extraction, on-line plasma extraction, enhanced mass reso-lution, atmospheric pressure photoionization, high-field asymmetric waveform ion mobility spectrometry, electron captureatmospheric pressure chemical ionization, enhancing MS detection via formation of anionic and cationic adducts, chemi-cal derivatization, ultra-performance chromatography, hydrophilic interaction chromatography, and MS-friendly ion-pairreversed-phase chromatography. In the end, we discuss potential pitfalls in LC-MS/MS bioanalysis and the means toavoid them. Such pitfalls may occur due to mass spectral interference from metabolites or prodrugs, due to the use of in-appropriate calibration standard and quality control samples for analysis involving unstable drugs or metabolites, and dueto the wild card phenomenon commonly known as the matrix effect.