Determination of three metabolites of a new angiotensin-converting enzyme inhibitor, imidapril, in plasma and urine by gas chromatography—mass spectrometry using multiple ion detection

doi:10.1016/0378-4347(92)80448-Y

Journal of Chromatography B: Biomedical Sciences and Applications

Volume 581, Issue 1, 2 October 1992, Pages 65-73

https://doi.org/10.1016/0378-4347(92)80448-Y Get rights and content

Abstract

A specific and sensitive gas chromatographic—mass spectrometric method for the determination of three metabolites of the angiotensin-converting enzyme inhibitor, imidapril, in plasma and urine was developed. The metabolites were isolated from plasma and urine using a Bond Elut C₁₈ solid-phase extraction cartridge. The isolated metabolites were converted to sensitive derivatives by pentafluorobenzyl bromide and heptafluoro-n-butyric acid anhydride. Following derivatization, the sample solutions were analysed by wide-bore column gas chromatography—mass spectrometry with multiple ion detection. The detection limits of the three metabolites were each 1 ng/ml in plasma and 5 ng/ml in urine. Analysis of the spiked plasma and urine samples demonstrated the good accuracy and precision of the method. This method was very useful for use in pharmacokinetic and bioavailability studies of the three metabolites of imidapril in humans.

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Determination of a novel ACE inhibitor in the presence of alkaline and oxidative degradation products using smart spectrophotometric and chemometric methods
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Citation Excerpt :
Imidaprilat shows about a 500 times higher activity than the ester form, IMD [2]. From the literature survey on the subject, many methods have already been tested including HPLC and GC methods with the use of MS detector [3–7], chiral LC method [2], other HPLC methods [8,9], densitometry [1] and spectrophotometric determinations [8,10]. With the intent of improving the quality of the active pharmaceutical ingredient (API) and its formulation, there is an increasing need of separation, identification, quantification, and characterization of the most possible degradation products generated under the various ICH guidelines for forced degradation [11].
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.
Validated liquid chromatographic determination of a novel ACE inhibitor in the presence of its hydrolytic and oxidative degradation products as per ICH guidelines
2014, Talanta
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Imidaprilat plasma level increases gradually and slowly declines [2]. IMD is a non-official drug which has only few reported methods for its determination such as UV spectrophotometry [3,4], HPLC and GC [4–10], an enantioselective chiral LC method [11] and TLC-densitometric method [12]. While, no stability studies or stability indicating analytical methods have been reported.
Imidapril hydrochloride (IMD) is a recently developed prodrug-type angiotensin-converting enzyme (ACE) inhibitor. Due to its instability under both hydrolytic and oxidative conditions, development of rapid, simple and sensitive methods for its determination in the presence of its possible degradation products is essential. We proposed two simple liquid chromatographic methods associated with ultraviolet detection. The first method is an HPTLC-densitometric one in which separation of IMD from its degradation products was achieved followed by densitometric scanning at 220 nm using silica gel F₂₅₄ plates and chloroform:ethanol:acetic acid (3:0.5:0.1, v/v/v) as the developing system. The second method was based on RP-HPLC in which the separation was performed using C18 analytical column and isocratic elution system with acetonitrile: 0.15% triethylamine (pH=2.2) (40:60, v/v). The optimum flow rate was 1.5 mL min⁻¹ and the detection was at 220 nm. Validation was conducted in compliance with the ICH guidelines and the methods were successfully applied for IMD determination in its commercial tablets. The obtained results were statistically compared to those obtained by applying reported HPLC method where no significant difference was found in accordance with accuracy and precision.
An overview of chromatographic methods coupled with mass spectrometric detection for determination of angiotensin-converting enzyme inhibitors in biological material
2007, Journal of Pharmaceutical and Biomedical Analysis
Gas and liquid chromatography–mass spectrometry (GC–MS, LC–MS) methods for the determination of angiotensin-converting enzyme inhibitors (ACEIs) and their metabolites in biological material have been reviewed. Since 1980s those hyphenated techniques have been applied to quantitate ACE inhibitors and the dynamic increase in the number of relevant publications can be observed in recent years. Although most of the methods available in the literature were analyses of plasma or serum, assays of blood and urine were also included. Additionally, sample pretreatment methods, separation conditions and ionization modes were overviewed. Some information on chemical structures, cis–trans izomerization and stability of compounds in question was also included. Most of the reported methods were successfully applied to the pharmacokinetic studies in humans.
The analysis of drugs in biological fluids, second edition
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Determination of three metabolites of a new angiotensin-converting enzyme inhibitor, imidapril, in plasma and urine by gas chromatography—mass spectrometry using multiple ion detection

Abstract

J. Chromatogr.

J. Chromatogr.

Arzneim.-Forsch.

Drug Metab. Dispos.