Effect of column temperature on the behaviour of some angiotensin converting enzyme inhibitors during high-performance liquid chromatographic analysis

The chromatographic behaviour of the ACE inhibitors lisinopril, enalapril a nd its two degradation products, enalaprilat (hydrolytic degradation produc t) and diketopiperazine (DKP) (cyclization degradation product) was studied as a function of column temperature and pH of the mobile phase. The rate o f isomerization (which influences the peak shape or even peak splitting dur ing chromatographic analysis) increases with temperature. The shape of the chromatographic peak for enalapril, enalaprilat and lisinopril is also pH d ependent. At high temperature (80 degreesC) and low pH (pH=2) all studied c ompounds appear on the chromatogram as a narrow chromatographic peak. Chrom atographic peaks become broader or they split by lowering the colunm temper ature. Enalapril appears at 6 degreesC on the chromatogram in two peaks whi ch belong to its cis- and brans-rotation isomers, Separation of the rotamer s was confirmed by NMR spectroscopy. (C) 2001 Elsevier Science B.V. All rig hts reserved.