This improved sample preparation method allows for the quantitative measurement of Benzodiazepines in urine. Benzodiazepines are psychoactive drugs that enhance the effect of the neurotransmitter GABA at the GABAA receptor. The urine samples were prepared using the eXtreme|FV®, followed by LC/MS/MS analysis. The most critical aspects of reliable urine analysis are the reduction of interferences from the sample matrix and analyte recovery. eXtreme|FV®, were compared to SPE for sample preparation to reduce the sample matrix causing interference prior to analysis. SPE is time consuming, adversely impacts recovery, uses large amounts of solvent and are expensive. The improved sample preparation method using the Thomson eXtreme|FV® allows for the analysis of 9 Benzodiazepines.