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Chromatography and mass spectrometry based techniques are the most commonly employed procedures to quantitate the analytes in pharmaceutical research. However, sensitivity of analytical methods significantly varies due to the difference in physicochemical characteristics of analytes. Sensitivity of methods greatly affects the quality of analytical results. Establishment of a sufficiently sensitive method ensures the suitability of a technique for its intended purpose. Although various types of advancement in chromatographic science are witnessed, issues related to sensitivity remain a major challenge for the analyte with low detection limit. Highly sensitive analytical methods are specifically essential to quantitate the analytes in the samples from dissolution study of sustained release formulations, cross-contamination study, impurity analysis, metabolite profiling, bioanalysis of highly potent and low bioavailable drugs. In recent years, huge involvement of researchers toward sensitivity enhancement of quantitative methods is evidenced. Wide verities of approaches are being reported in the field. Derivatization technique, introduction of ion-pairing reagents, sample pretreatment, and utilization of innovative methods such as 2-dimensional liquid chromatography, nano liquid chromatography, 2-dimensional gas chromatography, supercritical fluid chromatography, use of microcolumn are some approaches that are being employed. Online sample preparation techniques can significantly improve the sensitivity of a method by reducing sample loss and degradation. This review summarizes and critically discussed the approaches to improve the sensitivity of chromatographic and mass spectrometry based analytical methods. This article can guide the researchers to select suitable approaches for achieving the desired detection limit of analytical and bioanalytical methods based on their specific requirements.

Innovation in Strategies for Sensitivity Improvement of Chromatography and Mass Spectrometry Based Analytical Techniques