Study of the cis–trans isomerization of enalapril by reversed-phase liquid chromatography

Dynamic capillary electrophoresis (DCE) and computer simulation of the elution profiles with the stochastic model has been applied to determine the isomerization barriers of the angiotensin converting enzyme inhibitor enalaprilat. The separation of the rotational cis-trans isomeric drug has been performed in an aqueous 20 mM borate buffer at pH 9.3. Interconversion profiles featuring plateau formation and peak broadening were observed. To evaluate the rate constants k(cis-->trans) and k(trans-->cis) of the cis-trans isomerization from the experimental electropherograms obtained by dynamic capillary electrophoresis, elution profiles were analyzed by a simulation with iterative convergence to the experimental data using the ChromWin software which requires the total migration times of the individual isomers t(R), the electroosmotic break-through time t(0), the plateau height h(plateau), the peak widths at half height of the individual isomers w(h), as well as the peak ratio of the isomers as experimental data input. From temperature-dependent measurements between 0 degrees and 15 degrees C the thermodynamic parameters Delta G, Delta H and Delta S, the rate constants k(cis-->trans) and k(trans-->cis) and the kinetic activation parameters Delta G*, Delta H*, and Delta S* of the cis-trans isomerization of enalaprilat were obtained. From the activation parameters the isomerization barriers at 37 degrees C were calculated to be Delta G* (trans-->cis) = 87.2 kJ.mol(-1) and Delta G*(cis-->trans) = 91.9 kJ.mol(-1).

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“…Fig. 1) has been previously described by several authors using HPLC [20,21] and CE [22]. All authors describe the characteristic elution …”

mentioning

confidence: 81%

“…The thermodynamic parameters of the isomerization of enalaprilat (pH 9.3) were determined by a linear regression of the thermodynamic Gibbs free energies DG(T) vs. the corresponding temperatures T (correlation coefficient r = 0.9993) to be DH cis/trans = 3.4 kJ?mol 21 and DS cis/trans = 26 J? (K?mol) 21 .…”

Section: Isomerizationmentioning

confidence: 99%

Determination of the cis‐trans isomerization barrier of enalaprilat by dynamic capillary electrophoresis and computer simulation

Trapp

Schurig

2004

Electrophoresis

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“…These include spectrophotometric methods, [6][7][8][9] flow-injection spectrophotometric, 10 infrared method, 11 potentiometric selective membrane electrode methods, 12,13 NMR, 14 GC, 15 GCL/MS, 16 HPLC, [17][18][19][20][21][22][23][24][25][26][27] capillary electrophoresis, [28][29][30][31] radioenzymic 32 and radioimmunoassay. 33 Reviewing the literature revealed that up to the present time nothing has been published concerning the CL determination of enalapril maleate.…”

Section: Enalapril [(S)-1-(n-[1-(ethoxycarbonyl)-3-phenylpropyl]-lalamentioning

confidence: 99%

Flow-Injection Chemiluminescence Determination of Enalapril Maleate in Pharmaceuticals and Biological Fluids Using Tris(2,2′-bipyridyl)ruthenium(II)

Alarfaj

2003

ANAL. SCI.

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Enalapril maleate is a relatively new oral angiotensinconverting enzyme (ACE) inhibitor. Enalapril maleate, like its first-generation relative, captopril, has been shown to be effective in the treatment of hypertension and congestive heart failure. Enalapril [(S)-1-(N-[1-(ethoxycarbonyl)-3-phenylpropyl]-Lalanyl)-L-proline] is a prodrug which is de-esterified in the hepatic system to an active diacid form. 2 The drug is official in the USP 24. 3 The methods of analysis of the bulk drug and its tablets are high-performance liquid chromatography (HPLC) methods. It is also official in the European Pharmacopoeia 4 by a potentiometric titration method using sodium hydroxide.Other than the published analytical profile, 5 several methods have been reported for the analysis of enalapril maleate either in pure form, in pharmaceutical preparations, in biological fluids, or in mixture with other drugs. These include spectrophotometric methods, 33 Reviewing the literature revealed that up to the present time nothing has been published concerning the CL determination of enalapril maleate.Ru(bipy) 3 2+ is an extremely versatile base reactant for a variety of CL processes, and has also recently become a useful CL reagent. The process involves the oxidation of Ru(bipy)3 2+to Ru(bipy) 3 3+ , which is then followed by reduction with an analyte species to produce the emission of light. 34 There have been a variety of methods employed to obtain the active oxidized reagent Ru(bipy) 3 3+ .These include chemical, photochemical, electrochemical oxidation and in situ electrochemiluminescence.An analytical evaluation of commercially significant pharmaceutical drugs using Ru(bipy) 3 3+-CL detection has attracted considerable attention. A comprehensive review of the analytical applications of Ru(bipy) 3 3+ as a chemiluminescent reagent from 1978 to mid 1998 has been represented by Gerardi et al. 34The present paper describes the development of a simple flow-injection chemiluminometric method for the determination of enalapril maleate based on the chemical generation of Ru(bipy) 3 3+ by mixing two streams containing solutions of Ru(bipy) 3 2+ and acidic KMnO4. The experimental conditions for the reaction were optimized, and the final procedure allowed the successful determination of the studied drug in pharmaceuticals and biological fluids. Experimental Apparatus and manifoldThe flow system used for the determination and CL detection of enalapril maleate is shown schematically in Fig. 1. It consisted of a Gilson Minipuls 3MP4 peristaltic pump (two channels, variable speed) which was used to drive the carrier and the reagent streams through the flow system. Each stream was pumped at a constant flow rate using PTFE tubing (0.8 mm i.d.). The drug solution (250 µl) was injected through the sample injection valve, which allowed mixing of the sample with an acidified 1 × 10 -3 mol/l KMnO4 solution, and then combination with a 1 × 10 -2 mol/l Ru(bipy) 3 2+ solution in a Tshaped piece before entering the flow cell. The flow cell was a coil made of ...

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“…This chemical interconversion can occur during sample preparation or on-column and may be influenced by the mobile phase or the stationary phase. The types of reactions that may occur include acid or base catalyzed reactions and isomerization [20][21][22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Kinetic study on the epimerization of trityloxymethyl butyrolactol by liquid chromatography

Thompson

Sowa

et al. 2004

Journal of Chromatography A

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Study of the cis–trans isomerization of enalapril by reversed-phase liquid chromatography

Cited by 50 publications

References 20 publications

Determination of the cis‐trans isomerization barrier of enalaprilat by dynamic capillary electrophoresis and computer simulation

Determination of the cis‐trans isomerization barrier of enalaprilat by dynamic capillary electrophoresis and computer simulation

Flow-Injection Chemiluminescence Determination of Enalapril Maleate in Pharmaceuticals and Biological Fluids Using Tris(2,2′-bipyridyl)ruthenium(II)

Kinetic study on the epimerization of trityloxymethyl butyrolactol by liquid chromatography

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