The tandem mass spectrometry coupled with chromatography has been widely used for the analysis of urinary metabolites of compounds found in tobacco smoke. The purpose of this project was to simplify sample preparation procedures and, at the same time, to Increase sample throughput without sacrificing method sensitivity. For arylamines, the improved method resulted in the isolation and quantification of 2 additional compounds (i.e. aminonaphthalene and 3-aminobiphenyl) as compared to the reference method. The automation of liquid phase extraction step allowed an increased sample throughput, The introduction of an additional clean up step after derivatization resulted in cleaner samples and less maintenance of the detection system. Method sensitivity was increased with limits of quantification below 7 pg/mL for all arylamines. The linear calibration range was from 14-2200 pg/mL. Method accuracy, based on recoveries of added arylamines (i.e. laboratory fortified matrix (LFM)), was 100+14 % for amounts ranging from 300 to 1500 pg/mL of urine. With respect to acrolein and crotonaldehyde, an automated single-step reversed-phase SPE procedure was developed for the analysis of urinary mercapturic acid derivatives 3-hydroxypropyl (HPMA) and 3-hydroxy-1-methylpropyl (HMPMA). The limits of quantification were 1.5 ng/mL and 16.2 ng/mL respectively with a coefficient of variation of less than15% for both analytes. Recoveries determined for nonsmoker's urine fortified between 18-460 ng/mL and 304-519 ng/mL (HMPMA) ranged from 85% to 110%.