title: The use of microcalorimetry and HPLC for the determination of degradation kinetics and thermodynamic parameters of Perindopril Erbumine in aqueous solutions.
abstract: Perindopril Erbumine (PER) is one of the newly used angiotensin-converting enzyme inhibitors (ACE inhibitors) and is used for the treatment of patients with hypertension and symptomatic heart failure. It has two main degradation pathways, i.e. the degradation by hydrolysis and the degradation by cyclization. An isothermal heat conduction microcalorimetry (MC) and high pressure liquid chromatography (HPLC) were used for the characterization of aqueous solutions of PER and its stability properties. The rates of heat evolved during degradation of perindopril were measured by MC as a function of temperature and pH and from these data rate constant and change in enthalpy of the reactions were determined. With the HPLC method the concentration of perindopril and its degradation products were measured as a function of time in aqueous solutions of different pH that were stored at different temperatures. We demonstrated that reactions of degradation of perindopril at observed conditions follow the first order kinetics. The Arrhenius equation for each pH was determined. At pH 6.8 only one degradation pathway is present, i.e. the degradation by hydrolysis. Degradation constants for this pathway calculated from MC data are in good agreement with those obtained from HPLC. MC as a non-specific technique was shown to be useful in studies of PER when one reaction was present in the sample and also when more chemical and physical processes were simultaneously running.
authors.affiliation: Krka, d.d., Novo mesto, Smarjeska cesta 6, 8501 Novo mesto, Slovenia. zvone.simoncic@krka.biz
authors.forename: Z
authors.initials: Z
authors.lastname: Simoncic
authors.forename: R
authors.initials: R
authors.lastname: Roskar
authors.forename: A
authors.initials: A
authors.lastname: Gartner
authors.forename: K
authors.initials: K
authors.lastname: Kogej
authors.forename: V
authors.initials: V
authors.lastname: Kmetec
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D002151:Calorimetry / Q000379:methods; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D020913:Perindopril / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D013816:Thermodynamics
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D019999:Pharmaceutical Solutions; D020913:Perindopril