Separation and Identification of Substituted Pyridine Analogues in Heat Labile Solutions of HI-6 Dichloride

摘要

Previous work, describing the chemical break-down of HI-6 dichloride (4 carbamoyl-2'-hydroxyiminomethyl-1, 1'-oxydimethylene-di-(pyridinium chloride)) in aqueous solution has produced greater insight into the reaction kinetics of this compound during the degradation process. Earlier studies showed that the fate of HI-6 in solution is directly related to pH, temperature and concentration formulation during preparation ad storage. Slight variation of the established guidelines required for maintaining a stable anticholinergic antidote reduces the desired effectiveness of HI-6 to act a safe therapeutic agent in reactivating organophosphorus-inhibited acetylcholinesterase. Thus, recognizing the early signs of an unstable or partially degraded formulation is an essential requirement for being assured that a safe and efficacious product is available for human use. Using ion-pair high-performance liquid chromatographic (HPLC) and desorption chemical-ionization mass spectrometric (DCI-MS) direct-probe techniques, degradative by-products formed during HI-6 exposure to elevated temperatures were separated, collected and later analyzed by mass spectrometry (MS) for their chemical identities. Keywords: HI-6 bis pyridinium oxime; Substituted pyridine analogues, Isonicotinic acid, Isonicotinamide, 4-pyridinecarboxaldehyde, Pyridine-2-aldehyde, Pyridine-2-aldoxime, 4-cyanopyridin and HPLC.