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Kinetic Study on the Isomerization of Perindopril by HPLC

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Abstract

The isomerization of perindopril has been investigated using dynamics chromatography and an unified equation introduced by Trapp that was based on stochastic and theoretical plate models to determine the energies. The isomerization rate constants and Gibbs activation energies of isomerization are directly calculated from chromatographic peak parameters, i.e., retention times of the inter-converting species, peak width at half height, and relative plateau height. From the rate constant \( k_{1}^{ue} (T) \), measured at variable temperatures, the kinetic eyring activation parameters ΔG #, ΔH # and ΔS # of isomerization of perindopril were obtained. By variation of the flow rate of the mobile phase, the expected independence of the isomerization barrier from the chromatographic time scale was demonstrated for the first time. The relationships between peak shape and chromatographic conditions, such as flow rate, temperature, pH, organic modifier, and β-cyclodextrin, such as an additive, were investigated. In addition, an NMR investigation on perindopril was described.

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References

  1. Trapp O, Schoetz G, Schurig V (2001) Determination of enantiomerization barriers by dynamic and stopped flow chromatographic methods. Chirality 13:403–417

    Article  CAS  Google Scholar 

  2. Martin A (1949) Some theoretical aspects of partition chromatography. Biochem Soc Symp 3:4–20

    Google Scholar 

  3. Trapp O (2008) A novel software tool for high throughput measurements of inter-conversion barriers: DCXplorer. J Chromatogr B 875:42–47

    Article  CAS  Google Scholar 

  4. Trapp O (2006) Unified Equation for access to rate constants of first-order reactions in dynamic and on-column reaction chromatography. Anal Chem 78:189–198

    Article  CAS  Google Scholar 

  5. Li L, Thompson R, Sowa JR, Clausen A, Dowling T (1043) Kinetic study on the epimerization of trityloxymethyl butyrolactol by liquid chromatography. J Chromatogr A 2004:171–175

    Google Scholar 

  6. Trapp O, Schurig V (2002) Novel direct access to enantiomerization barriers from peak profiles in enantioselective dynamic chromatography: enantiomerization of dialkyl-1,3 allenedicarboxylates. Chirality 14:465–535

    Article  CAS  Google Scholar 

  7. Krupcik J, Oswald P, Majek P, Sandra P, Armastrong DW (1000) Determination of inter-conversion energy barrier of enantiomers by separation method. J Chromatogr A 2003:779–800

    Google Scholar 

  8. Shoji A, Yanagida A, Shindo H, Ito Y, Shibusawa Y (2007) Counter-current chromatographic estimation of hydrophobicity of Z-(cis) and E-(trans) enalpril and kinetic of cis/trans isomerization. J Chromatogr A 1157:101–107

    Article  CAS  Google Scholar 

  9. Simon G, Moriaka S, Snyder DK, Cohon JN (1983) Increased renal plasma flow in long-term enalapril treatment of hypertension. Clin Pharmacol Ther 34:459–465

    Article  CAS  Google Scholar 

  10. Benidict CR (1999) Centrally acting antihypertensive drugs: Re-emergence of sympathetic inhibition in the treatment of hypertension. Curr Hypertens Rep 1:305–312

    Article  Google Scholar 

  11. Mutschler E, Derendorf H, Schhafer-Kortig K, Elord K, Esters S (1995) Drug actions. Basic principles and therapeutic aspects. Medpharm, Stuttgart, pp 385–475

    Google Scholar 

  12. Thomas WA, Williams MK (1972) 13 C nuclear magnetic resonance spectroscopy and cis/trans isomerism in dipeptides containing proline. J Chem Soc Chem Commun 17:994–999

    Article  Google Scholar 

  13. Grathwohl C, Kurt W (1981) NMR studies of the rates of proline cistrans isomerization in oligopeptides. Biopolymers 20:2623–2633

    Article  CAS  Google Scholar 

  14. Cardoza AL, Cutak JB, Ketter J, Larive CK (1022) High-performance liquid chromatographic-nuclear magnetic resonance investigation of the isomerization of alachlor-ethanesulfonic acid. J Chromatogr A 2004:131–137

    Google Scholar 

  15. Trabelsi H, Bouabdallah S, Sabbah S, Raouafi F, Bouzouita K (2000) Study of the cis-trans isomerization of enalapril by reversed-phase liquid chromatography. J Chromatogr A 871:189–199

    Article  CAS  Google Scholar 

  16. Bouabdallah S, Trabelsi H, Ben Dhia T, Sabbah S, Bouzouita K, Khaddar R (2003) RP-HPLC and NMR study of cis-trans isomerization of enalaprilat. J Pharm Biomed Anal 31:731–741

    Article  CAS  Google Scholar 

  17. Bouabdallah S, Trabelsi H, Bouzouita K, Sabbah S (2002) Reversed-phase liquid chromatography of lisinopril conformers. J Biochem Biophys Methods 54:391–405

    Article  CAS  Google Scholar 

  18. Jacobson J, Melander W, Vaisnys G, Horvath C (1984) Kinetic study on cis-trans proline somerization by high-performance liquid chromatography. J Phys Chem 88:4536–4542

    Article  CAS  Google Scholar 

  19. Melander WR, Jacobson J, Horvath C (1982) Effect of molecular structure and conformational change of proline-containing dipeptides in reversed-phase chromatography. J Chromatogr 234:269–276

    Article  CAS  Google Scholar 

  20. Henderson DE, Horvath C (1986) Low temperature high-performance liquid chromatography of cistrans proline dipeptides. J Chromatogr 368:203–213

    Article  CAS  Google Scholar 

  21. Qin XZ, Ip P, Tsai WE (1992) Determination and rotamer separation of enalapril maleate by capillary electrophoresis. J Chromatogr A 626:251–258

    Article  CAS  Google Scholar 

  22. Rathore AS, Horvath C (1997) CZE of inter-converting Cis-Trans conformers of peptidyl-proline dipeptides: estimation of the kinetic parameters. Electrophoresis 18:2935–2943

    Article  CAS  Google Scholar 

  23. Gustafsson S, Eriksson B-M, Nilsson I (1990) Multiple peak formation in reversed-phase liquid chromatography of ramipril and ramiprilate. J Chromatogr 506:75–83

    Article  CAS  Google Scholar 

  24. Hana R, Wada A (1987) Analysis of the cistrans isomerization kinetics of—alanyl—proline by the elution-band relaxation method. J Chromatogr 394:273–278

    Article  Google Scholar 

  25. Salamoun J, Slais K (1991) Elimination of peak splitting in the liquid chromatography of the proline-containing drug enalapril maleate. J Chromatogr 537:249–264

    Article  CAS  Google Scholar 

  26. Qin X-Z, DeMacro J, Ip DP (1995) Simultaneous determination of enalapril, felodipine and their degradation products in the dosage formulation by reversed-phase high-performance liquid chromatography using a Spherisorb C8 column. J Chromatogr 707:245–254

    Article  CAS  Google Scholar 

  27. Tanaka N, Goodell H, Karger BL (1978) The role of organic modifiers on polar group selectivity in reversed-phase liquid chromatography. J Chromatogr 158:233–248

    Article  CAS  Google Scholar 

  28. Klaas B, Horvath C, Melander WR, Nahum A (1981) Surface silanols in silica-bonded hydrocarbonaceous stationary phases. J Chromatogr 203:65–84

    Article  Google Scholar 

  29. Kalman A, Thunecke F, Schmidt R, Schiller PW, Horvath C (1996) Isolation and identification of peptide conformers by reversed-phase high-performance liquid chromatography and NMR at low temperature. J Chromatogr 729:155–171

    Article  CAS  Google Scholar 

  30. Salamoun J, Slais K (1991) Elimination of peak splitting in the liquid chromatography of the proline-containing drug enalapril maleate. J Chromatogr 537:249–3067

    Article  CAS  Google Scholar 

  31. Kroeff EP, Pietrzyk DT (1978) Investigation of the retention and separation of amino acids, peptides, and derivatives on porous copolymers by high performance liquid chromatography. Anal Chem 50:502–511

    Article  CAS  Google Scholar 

  32. Friebe S, Krauss GJ, Nitsche H (1992) High-performance liquid chromatographic separation of cis-trans isomers of proline-containing peptides: I separation on cyclodextrin-bonded silica. J Chromatogr 598:139–142

    Article  CAS  Google Scholar 

  33. Friebe S, Hartrodt B, Neubert K, Krauss GJ (1994) High-performance liquid chromatographic separation of cistrans isomers of proline-containing peptides: II fractionation in different cyclodextrin. J Chromatogr A 661:7–12

    Article  CAS  Google Scholar 

  34. Bonazzi D, Gotti R, Andrisano V, Carvini V (1997) Analysis of ACE inhibitors in pharmaceutical dosage forms by derivative UV spectroscopy and liquid chromatography (HPLC). J Pharm Biomed Anal 16:431

    Article  CAS  Google Scholar 

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Bouabdallah, S., Trabelsi, H., Dhia, M.T.B. et al. Kinetic Study on the Isomerization of Perindopril by HPLC. Chromatographia 75, 1247–1255 (2012). https://doi.org/10.1007/s10337-012-2311-8

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