Since its inception as a tool of analytical chemistry, LC-MS/MS spread rapidly and indeed continues to do so in (amongst others) bioanalytical fields. One of the advantages of the technique is its selectivity for many analytes of interest. However, this high selectivity could lead to a misconception that it is always possible to simplify or (on occasion) almost completely remove the necessity for extensive sample preparation.  However, during and after uptake by bioanalytical laboratories worldwide, it became apparent that there were inherent problems with detection of relatively small analyte concentrations in the complex sample matrices associated with biological fluids (e.g. blood and  urine).