Due to the presence of endogenous components in biofluids, ionization suppression or enhancement may occur for bioanalytical assays using LC-MS or LC-MS/MS technologies. The matrix effect may affect the precision and accuracy of a bioanalytical method and, therefore, compromise the quality of the results. Protein precipitation sample preparation along with LC-MS/MS is a high-throughput method most commonly used in bioanalysis and is largely affected by the matrix effect. In order to eliminate the matrix effect during the method development, some considerations may be used: cleaner sample preparations, more sensitive instruments, which allow less material to be injected, different chromatographic separations and much more must be investigated. More than giving tools to adequately assess the matrix effect during the method development, this review gives scientists numerous ways to eliminate or reduce the matrix effect based on novel sample-preparation techniques, new chromatographic optimization methods and new technologies.
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