title: Studies on the instability of chlorhexidine, part I: kinetics and mechanisms.
abstract: The objectives of the studies presented herein were to determine the pH-dependent chlorhexidine (CHD) degradation scheme, to determine the rate laws, and to propose reasonable mechanisms for CHD hydrolysis in aqueous solutions. A series of degradation kinetic studies was conducted at 90.0 °C using reaction mixtures containing 0.10 mM CHD prepared in the pH range of 0.5-9.0 using hydrochloric acid, sodium hydroxide, acetate, phosphate, or 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffers at a constant ionic strength of 0.500 M. Concentration-time profiles for all degradation products, intermediates, and substrates were determined by high-performance liquid chromatography (HPLC). Degradation products and intermediates were identified using a combination of liquid chromatography-mass spectrometry, kinetic analysis, and HPLC comparison with authentic compounds. pH-dependent degradation scheme and rate laws were parameterized using nonlinear regression. The direct formation of p-chloroaniline (PCA) from CHD is the major pathway in acidic conditions, whereas the indirect formation of PCA via the formation of p-chlorophenylurea is the main pathway in alkaline conditions.
authors.affiliation: College of Pharmacy, The University of Iowa, Iowa City, Iowa 52241, USA.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Zong
authors.forename: Lee E
authors.initials: LE
authors.lastname: Kirsch
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D000891:Anti-Infective Agents, Local / Q000737:chemistry*; D002710:Chlorhexidine / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics
chemical_list: D000814:Aniline Compounds; D000891:Anti-Infective Agents, Local; D002710:Chlorhexidine; C004658:4-chloroaniline