Electrospun tissue engineering scaffolds provide mechanical support to seeded cells that populate the structure while depositing specific extracellular matrix components. The potent sterilizing agent 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) is often used in electrospinning investigations involving biologically-derived polymers. Surprisingly, there has been no study of solvent retention versus composition even though materials selection should influence organic solvent content. We developed a method quantifying HFIP retention following electrospinning of gelatin, polycaprolactone (PCL), and PCL-gelatin blends using electro-spray mass spectroscopy. The acetone content of ace- tone-spun PCL was also established. Pure gelatin fiber contained as much as 1600 ppm of HFIP. In contrast, little acetone or HFIP was detected in 100% PCL. Gelatin clearly has a greater affinity for HFIP than PCL and materials selection has a strong influence on the amount of retained solvent. Vacuum + heat treatment at 37 and 45 degrees C reduced [HFIP] to 10 and 5.6 ppm, respectively, levels having no demonstrated effects on mammalian cell viability. (c) 2007 Wiley Periodicals, Inc.