[15�C23] Bioanalytical data generated in discovery and pre-clinical programs are a valuable guide to early clinical programs. Plasma concentration-response data from these programs can be compared with those obtained in man. Such comparisons are particularly valuable during the phase one-initial dose escalation study. To maximize this, it is our practice to generate PK data between each dose increase.[24] BIOANALYSIS Bioanalysis is a term generally used to describe the quantitative measurement of a compound (drug) or their metabolite in biological fluids, primarily blood, plasma, serum, urine or tissue extracts.[25] A bioanalytical method consists of two main components Sample preparation: Sample preparation is a technique used to clean up a sample before analysis and/or to concentrate a sample to improve its detection. When samples are biological fluids such as plasma, serum or urine, this technique is described as bioanalytical sample preparation. The determination of drug concentrations in biological fluids yields the data used to understand the time course of drug action, or PK, in animals and man and is an essential component of the drug discovery and development process.[26] Most bioanalytical assays have a sample preparation step to remove the proteins from the sample. Protein precipitation, liquid�Cliquid extraction and solid phase extraction (SPE) are routinely used.[27] Detection of the compound: The detector of choice is a mass spectrometer.[26] Currently, the principle technique used in quantitative bioanalysis is high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) using either electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI) techniques.[28] The triple quadrupole (QqQ) mass spectrometer (MS), when operated in the selected reaction monitoring (SRM) mode, offers a unique combination of sensitivity, specificity and dynamic range. Consequently, the QqQ MS has become the instrument of choice for quantitation within the pharmaceutical industry. Since ESI and APCI can be operated at flow rates as high as 1 and 2 mL/min, respectively, most of the convenience columns (e.g., C18, C8, C4, phenyl, cyanopropyl) are compatible. Recent technological advances have made 1.7 ��m particle size packing material available. Coupling with high pressure pump and high-speed acquisition MS, ultra-high pressure liquid chromatography (UPLC) offers unique high-throughput and resolving power to obtain maximum chromatographic performance and superior assay sensitivity.[29] Before a bioanalytical method can be implemented for routine use, it is widely recognized that it must first be validated to demonstrate that it is suitable for its intended purpose. A GLP (Good Laboratory Practices) validated bioanalytical method is needed to support all development studies (e.g., toxicology studies and human clinical trials).