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

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Abstract
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 quatitatively to its reported in vivo degradation in animals and man. It is concluded that l-PAM does not undergo important, active in vivo metabolism.