Stability of Lidocaine in Aqueous Solution: Effect of Temperature,pH, Buffer,and Metal Ions on Amide Hydrolysis |
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Authors: | Michael F. Powell |
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Affiliation: | (1) Institute of Pharmaceutical Sciences, Syntex Research, Palo Alto, California, 94304 |
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Abstract: | The degradation of lidocaine in aqueous solution obeys the expression kobs = (kH+[H +] + ko ) [H+]/([H + ] + Ka + koKa([H + ] + Ka) where kH+ is the rate constant for hydronium ion catalysis, and ko and ko are the rate constants for the spontaneous (or water-catalyzed) reactions of protonated and free-base lidocaine. At 80°C, the rate constants for these processes are 1.31 × 10–7M–l sec–1, 1.37 × 10–9 sec–1, and 7.02 × 10–9sec–1; the corresponding activation energies are 30.5, 33.8, and 26.3 kcal mol–1, respectively. It was found that the room temperature pH of maximum stability is 3–6 and that lidocaine is more reactive in the presence of metal ions such as Fe2+ and Cu2+. The dissociation constant, Ka, for lidocaine at 25–80°C was also measured at 0.1 M ionic strength and a plot of pKa versus 1/T gave a slope of (1.88 ± 0.05) × 103 K–1 and intercept 1.56 ± 0.16. |
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Keywords: | kinetics of lidocaine degradation aqueous stability pKa amide hydroylsis |
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