Forced Degradation Study of Quinapril by UPLC-DAD and UPLC/ MS/MS: Identification of By-products and Development of Degradation Kinetics

Dendeni, M.; Cimetière, Nicolas; Huguet, Samuel; Amrane, Abdeltif; Hamida, Najib Ben

doi:10.2174/1573412911309030006

Cited by 2 publications

(1 citation statement)

References 42 publications

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“…Diclofenac, flupirtine and quinapril degrade to cyclized products, and formation of these products are reported to occur through formation of an amide bond between a carboxylic acid and an amino group in acidic medium ( Figure 18). 141,51,71 However, these routes seem improbable because the amino group is protonated in acidic medium destroying the nucleophilic character of amino nitrogen. Moreover, in diclofenac, presence of two chloro groups ortho to the -NH-group further intensifies the electron deficiency on the nitrogen.…”

Section: 105mentioning

confidence: 99%

Understanding unconventional routes to impurities from drugs in hydrolytic conditions

Kaur¹,

Bansal²,

Bansal³

2016

IJPER

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Introduction: Hydrolytic degradation is the most common cause of formation of impurities or degradation products in drugs during different stages of drug product development and/or shelf life of the drug/product. Degradation products formed by hydrolysis of ester, amide, urethane, sulfonamide, sulfonate and ether linkages, and of nitrile, hydroxyl and amino groups in drugs can be conveniently predicted and identified. Many drugs are known to degrade to such expected conventional hydrolytic degradation products, and the mechanisms of such degradations are also well known and reported. However, many drugs are reported to degrade under hydrolytic conditions to products, which cannot be justified by the conventional hydrolytic reactions. Objectives: Though structures of such unconventional hydrolytic products can be characterized through different spectral techniques, but there is a need to understand the mechanisms of such unconventional hydrolytic reactions in order to help in establishing intrinsic stability characteristics of a drug. Methodology: In the present review, we have studied and critically analysed all possible reports on hydrolytic degradation of various dugs to provide a thorough insight into unconventional routes of hydrolytic degradations of drugs. The various unconventional hydrolytic reactions found responsible for degradation of drugs are classified as oxidation, dehydrogenation, coupling/condensation, N-alkylation, C-C bond cleavage, C-N bond cleavage, dehalogenation, cyclization, decarboxylation and hydroxylation. Discussion: Varied types of reactions under hydrolytic conditions are triggered/controlled by the nature of substituent(s) across or around the susceptible bonds/groups. The mechanisms for such unconventional hydrolytic reactions have been discussed or proposed with support from the standard literature. The contents are expected to enable an analyst and a drug formulator to predict various possible as well as seemingly improbable hydrolytic degradation products of a drug well ahead of systematic forced degradation studies.

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Section: 105mentioning

confidence: 99%

Understanding unconventional routes to impurities from drugs in hydrolytic conditions

Kaur¹,

Bansal²,

Bansal³

2016

IJPER

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Investigation of the Rotational Isomerism of Quinapril and Quinaprilat by UPLC–DAD and Elucidation of the Conformational Equilibrium by NMR

Dendeni

Cimetière²,

Soutrel³

et al. 2015

Aust. J. Chem.

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Quinapril and quinaprilat are two angiotensin-converting enzyme inhibitors (ACEIs) characterized by a peak broadening and splitting when they were analyzed by ultra-performance liquid chromatography (UPLC). This phenomenon is due to the existence of the two isomers cis and trans around the amide band. In order to confirm the existence of the two conformers and allow identification of the predominant form, NMR studies of quinapril, involving 1H, 13C, 1H-1HCOSY, Impact-HMBC, JMOD, HSQC, and ROESY have been conducted in this work. The analyses allowed us to identify the predominant form of quinapril; the conformer trans is the predominant form (75 %). In addition, this study highlights the important benefits of UPLC to separate quinapril and quinaprilat isomers due to its high resolving power. The effect of various operating conditions on the retention peak, namely, splitting and band broadening of quinaprilat and quinapril, has been qualitatively examined in this study. Several practical experimental conditions have been tested, allowing both the elution of the two ACEIs as single peaks, while keeping at the same time an acceptable separation. The effect of various factors on the conformational s-cis–s-trans equilibrium of quinapril and quinaprilat, namely, the composition of the mobile phase, column temperature, flow rate, pH, and type and amount of organic modifier was investigated by UPLC–DAD (diode array detector) with a BEH C18 column (100 mm, 2.1 mm internal diameter × 1.7 µm particle diameter). Several deconvolution models were used to model overlapped peaks and to determine resolution. Results obtained showed that a mobile phase consisting of ammonium buffer (10 mM; pH 8) and acetonitrile allows the separation of the quinapril and quinaprilat conformers. Maximum resolution was obtained for a composition of mobile phase (55/45) and (65/35) (ammonium buffer/acetonitrile, v/v) for quinapril and quinaprilat, respectively at 45°C and flow rates of 0.4 and 0.5 mL min–1.

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Forced Degradation Study of Quinapril by UPLC-DAD and UPLC/ MS/MS: Identification of By-products and Development of Degradation Kinetics

Cited by 2 publications

References 42 publications

Understanding unconventional routes to impurities from drugs in hydrolytic conditions

Understanding unconventional routes to impurities from drugs in hydrolytic conditions

Investigation of the Rotational Isomerism of Quinapril and Quinaprilat by UPLC–DAD and Elucidation of the Conformational Equilibrium by NMR

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