Usually, serum or plasma is used for the measurement of concentration of a drug of interest for the purpose of therapeutic drug monitoring (TDM). However, monitoring whole blood concentrations of certain drugs such as various immunosuppressants is clinically more relevant. During the 1950s, TDM of antiepileptic drugs was performed using gas chromatography (GC). Several bioassays were available for monitoring certain antibiotics. In the 1960s, extensive research took place to develop various assays for therapeutic drugs using high-performance liquid chromatography (HPLC). In the 1970s, immunoassays were available for accurate determination of concentrations of various drugs in serum and plasma, thus revolutionizing the field of TDM. Immunoassays are widely used in clinical laboratories for routine drug monitoring because of ease of operation, simplicity, and speed. However, immunoassays are not commercially available for all drugs currently monitored in clinical practice, and various sophisticated techniques such as HPLC combined with tandem mass spectrometry or GC combined with mass spectrometry are used for determination of concentrations of these drugs in biological matrix. Usually, such specialized tests are offered in reference laboratories, academic based hospital laboratories, and clinical laboratories of larger hospitals.

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