RESUMO
Paclitaxel, a unique antimitotic chemotherapy agent that inhibits cell division by binding to microtubules and prevents them from "depolymerizing," has received widespread interest because of its efficacy in fighting certain types of cancer, including breast and ovarian cancer. Paclitaxel undergoes aggregation at millimolar concentrations in both aqueous media and solvents of low polarity (mimicking hydrophobic environments). Its aggregation may have impact on its aqueous stability and its ability to stabilize microtubules. Here, we investigated the dimerization phenomenon of paclitaxel by electrospray ionization mass spectrometry (ESI-MS). Paclitaxel dimers were stable in solutions of acetonitrile/aqueous ammonium acetate (80/20) and aqueous sodium acetate/acetonitrile (92/8 or 95/5) at various pH values. Additional experiments using solution-phase hydrogen/deuterium exchange were employed to ascertain whether or not the observed dimers were formed in solution or as an artifact of the ESI process by ion-molecule reaction. The evidence supports formation of the dimer in solution, and the approach used can be extended to investigation of other types of drug-drug interactions.
