| 主权项 |
1. A process for preparing a processed composition containing a pharmaceutical agent by removing a Michael acceptor contaminant from a composition containing a pharmaceutical agent to provide a processed composition comprising a reduced Michael acceptor content of less than 200 ppm which may be internalized by a living organism;
the method comprising the steps of:
treating the composition containing the Michael acceptor, or salt thereof, with a thiol-containing compound at a thiol and hydrogen ion concentration selected to yield the reduction in Michael acceptor as determined by the equilibrium expression:
[TM]/[M]=KR[T]t/(1+KSH[H+])wherein [TM] is concentration of thiol-Michael adduct, [M] is the concentration of Michael acceptor, [T]t is the total concentration of thiol-containing compound, [H+] is hydrogen ion concentration, KR is the equilibrium constant for the reaction, KSH is the acid dissociation constant for the thiol-containing compound;wherein the thiol-containing compound reacts with at least one Michael acceptor or salt thereof to provide a thiol-Michael adduct or salt thereof; andseparating the resulting thiol-Michael adduct or salt thereof from the composition by one or any combination of selective precipitation or extraction of the composition in order to provide a processed composition comprising a reduced Michael acceptor content of less than 200 ppm which may be internalized by a living organism;wherein the pharmaceutical agent is oxycodone, hydrocodone, oxymorphone, hydromorphone, naloxone, naltrexone, or an acceptable salt thereof, andwherein the Michael acceptor is an α,β-unsaturated ketone of oxycodone, hydrocodone, oxymorphone, hydromorphone, naloxone, naltrexone, or an acceptable salt thereof. |
