Rd. Skwierczynski et Ka. Connors, DEMETHYLATION KINETICS OF ASPARTAME AND L-PHENYLALANINE METHYL-ESTER IN AQUEOUS-SOLUTION, Pharmaceutical research, 10(8), 1993, pp. 1174-1180
The kinetics of demethylation of aspartame and L-phenylalanine methyl
ester were studied in aqueous solution at 25-degrees-C over the pH ran
ge 0.27-11.5. The pseudo-first-order rate constant for aspartame was r
esolved into individual contributions from methyl ester hydrolysis and
diketopiperazine formation. pH-rate profiles were quantitatively desc
ribed by chemically reasonable kinetic schemes. Aspartame is maximally
stable at pH 4 (t90 = 53 days at 25-degrees-C); phenylalanine methyl
ester, at pH 3. The potentiometrically measured pK(a) values were pK(a
1) 3.19 and pK(a2) 7.87 for aspartame and pK(a) 7.11 for phenylalanine
methyl ester.