Abiotic transformations and decomposition kinetics of 4-carbamoyl-2'-[(hydroxyimino)methyl]-1,1'-(oxydimethylene)-bis(pyridin ium chloride) in aqueous phosphate buffers.
The rate of disappearance of 4-carbamoyl-2'-[(hydroxyimino)methyl]-1,1'-(oxydimethylene) bis (pyridinium chloride) (HI-6) from aqueous phosphate buffers (pH 3.0-9.1) was both pH and temperature sensitive. In midrange buffers (pH 6.0-9.1, mu = 0.2 M) at 37, 25, or 4 degrees C the decomposition followed first-order kinetics consistent with hydroxide-promoted decomposition of the un-ionized drug or with hydrolysis of the ionized oxime anion to result in 4-carbamoyl-2'-hydroxy-1,1'-(oxydimethylene)bis(pyridinium) cation (intermediate 1). The subsequent conversion of intermediate 1 to 4-carboxy-2'-hydroxy-1,1'-(oxydimethylene)bis(pyridinium) cation (intermediate 2) followed higher order kinetics which were consistent with either acid- or base-promoted hydrolysis of the B-ring amide functionality. After approximately 138 days in the dark, the sum of the residual HI-6, intermediate 1, and intermediate 2 in the crude decomposition mixture accounted for 89.9 +/- 10.0% of the initial substrate. Minor byproducts included 4-carbamoyl-2'-carboxy-1,1'-(oxydimethylene)bis(pyridinium) cation, 2-pyridinealdoxime, 2-pyridinecarboxaldehyde, 2-hydroxypyridine, isonicotinamide, isonicotinic acid, and traces of cyanide. In addition, 2-cyanopyridine appeared to be a transient intermediate in more alkaline media. In total, this drug resembles other mono- and bis(pyridinium) aldoximes in terms of the decomposition routes in aqueous solutions at intermediate pHs.
Mdachi
R E
RE
Department of Food Science and Agricultural Chemistry, Macdonald College, Ste. Anne de Bellevue, Québec, Canada.
Marshall
W D
WD
Ecobichon
D J
DJ
Fouad
F M
FM
Connolley-Mendoza
C E
CE
D000931:Antidotes / Q000737:chemistry*; D002021:Buffers; D002801:Cholinesterase Reactivators / Q000737:chemistry*; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010091:Oximes; D010710:Phosphates; D011726:Pyridinium Compounds / Q000737:chemistry*; D013696:Temperature
D000931:Antidotes; D002021:Buffers; D002801:Cholinesterase Reactivators; D010091:Oximes; D010710:Phosphates; D011726:Pyridinium Compounds; C022870:asoxime chloride