We studied the cause of cracking of clinically used polyurethane (PU) catheters during the constant infusion of etoposide (VP-16) injection (Lastet inj.) without dilution. After the vehicles used for VP-16 injection, ethanol or polyethylene glycol 400 (PEG400), were infused into the PU catheters at a constant infusion rate (30 ml/h) for 24 h, obvious degradation of the internal wall of the catheter was observed under an electron microscope. When the PU catheter was immersed in ethanol for 24 h, condensed polymers of 1,4-butanediol (BD), contained in PU catheters as an elasticizer, were detected in the ethanol elute using the ESI/MS method. Moreover, time-dependent elution of BD from PU catheters with the infusion of ethanol into the catheter for 24 h at 30 ml/h was observed using the GC/MS method. The cumulative amount of BD eluted from the PU catheter with ethanol vehicle for 24 h was 130 micrograms. In conclusion, degradation and subsequent cracking of PU catheters during the infusion of VP-16 injection were caused by ethanol and PEG400 contained in the injection solution. Furthermore, to prevent the elution of BD from PU catheters, we suggest that PU catheters should not be used for the administration of VP-16 injection without dilution in consideration of safety and efficacy.