In vitro degradation of L-phenylalanine mustard (L-PAM)

L-Phenylalanine mustard (L-PAM), a bis-choroethylamine, is an important drug in the treatment of multiple myeloma and ovarian cancer. It undergoes rapid hydrolysis in vitro and in vivo, forming the mono-and dihydroxy degradation products. L-PAM's first-order disappearance rate in a phosphate-buffered solution did not differ statistically according to the presence or absence of activated rat liver microsomal enzymes. Furthermore, L-PAM's disappearance rate in a rat whole liver perfusion system was not greater than its hydrolysis rate in water. In vitro plasma recovery studies showed that up to 85% of the 14C L-PAM drug equivalents could be recovered as the parent compound and the mono- and dihydroxy degradation products. Thus, L-PAM in in vitro degradation was similar qualitatively and quantitatively to its reported in vivo degradation in animals and man. It is concluded that L-PAM does not undergo important, active in vivo metabolism.