Determination of a novel ACE inhibitor in the presence of alkaline and oxidative degradation products using smart spectrophotometric and chemometric methods

Abstract

Simple, accurate, sensitive and validated UV spectrophotometric and chemometric methods were developed for the determination of imidapril hydrochloride (IMD) in the presence of both its alkaline (AKN) and oxidative (OXI) degradation products and in its pharmaceutical formulation. Method A is the fourth derivative spectra (D4) which allows the determination of IMD in the presence of both AKN and OXD, in pure form and in tablets by measuring the peak amplitude at 243.0 nm. Methods B, C and D, manipulating ratio spectra, were also developed. Method B is the double divisor-ratio difference spectrophotometric one (DD-RD) by computing the difference between the amplitudes of IMD ratio spectra at 232 and 256.3 nm. Method C is the double divisor-first derivative of ratio spectra method (DD-DR1) at 243.2 nm, while method D is the mean centering of ratio spectra (MCR) at 288.0 nm. Methods A, B, C and D could successfully determine IMD in a concentration range of 4.0-32.0 µg/mL. Methods E and F are principal component regression (PCR) and partial least-squares (PLS), respectively, for the simultaneous determination of IMD in the presence of both AKN and OXI, in pure form and in its tablets. The developed methods have the advantage of simultaneous determination of the cited components without any pre-treatment. The accuracy, precision and linearity ranges of the developed methods were determined. The results obtained were statistically compared with those of a reported HPLC method, and there was no significant difference between the proposed methods and the reported method regarding both accuracy and precision.

Keywords: Chemometry; Double divisor–ratio derivative; Double divisor–ratio difference; Imidapril hydrochloride; Mean centering of ratio spectra.

Fig. 1

Chemical structure of IMD.

Fig. 2

HPTLC chromatograms of IMD (A), AKN (B) and OXI (C), using chloroform:ethanol:acetic acid (3:0.5:0.1, by volume) at 220 nm.

Fig. 3

IR spectra of IMD, AKN and OXI.

Fig. 4

MS spectra of IMD, AKN and OXI.

Fig. 5

Schemes of IMD degradation under alkaline (A) and oxidative (B) conditions.

Fig. 6

Zero order absorption spectra of IMD (12 µg/mL) and of its degradates, AKN and OXI (3 µg/mL each) using 0.1 M HCl as a solvent.

Fig. 7

The fourth derivative (D4) spectra of IMD (12 µg/mL) and of its degradates, AKN and OXI (3 µg/mL, each) using 0.1 M HCl as a solvent.

Fig. 8

Ratio spectra of IMD (12 µg/mL) and of its degradates, AKN and OXI (3µg/mL each) using DD as double divisor of AKN and OXI (3 µg/mL each) and 0.1 M HCl as a blank.

Fig. 9

The first derivative of the ratio spectra of IMD (12 µg/mL) and of its degradates, AKN and OXI (3 µg/mL each) using DD as double divisor of AKN and OXI (3 µg/mL each) and 0.1 M HCl as a blank.

Fig. 10

Mean centering of ratio spectra of IMD, 4–32 μg/mL in 0.1 M HCl using the spectra of its degradation products as divisor of AKN and OXI (3 µg/mL each).

Fig. 11

Root mean square error of calibration (RMSEC) plot of the cross validation results of the training set as a function of the number of principal components used to construct the PCR calibration.

Fig. 12

Root mean square error of calibration (RMSEC) plot of the cross validation results of the training set as a function of the number of principal components used to construct the PLS calibration.