This article reviews current methods used in quantitative analysis of pharmaceutical compounds
from whole blood matrix by liquid chromatography mass spectrometry. Whole blood matrix reviewed here
includes traditional liquid whole blood and dried blood spot (DBS) on a collection paper. A number of
bioanalytical methods have been reported over the years for the determination of pharmaceutical compounds
from liquid whole blood matrix. These methods have been used to support drug discovery and development
as well as therapeutic drug monitoring. Dried blood spot technique was initially developed for newborn
screening, later adapted to therapeutic drug monitoring, and now expanding into pharmaceutical drug
discovery and development. Sample pretreatment, extraction, chromatography, and mass detection
procedures for sample analysis from both liquid whole blood and dried blood spot are summarized in this
article. Factors influencing assay performance such as sampling and automation are discussed. Emerging
techniques allowing direct analysis of blood samples using mass spectrometry technique are also included.