Quantification of trandolapril and its metabolite trandolaprilat in human plasma by liquid chromatography/tandem mass spectrometry using solid‐phase extraction

Nirogi, Ramakrishna; Kandikere, Vishwottam; Shrivastava, Wishu; Mudigonda, Koteshwara

doi:10.1002/rcm.2794

Cited by 12 publications

(7 citation statements)

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“…An HPLC-MS/MS assay was developed to determine concentrations of the trandolapril active metabolite, trandolaprilat, based on a previously published method with some modifications [11]. The HPLC-MS/MS analytical system consisted of a Shimadzu Prominence HPLC system and an Applied Biosystems API 4000 QTRAP ® mass spectrometer.…”

Section: Methodsmentioning

confidence: 99%

CES1P1 variant −816A>C is not associated with hepatic carboxylesterase 1 expression and activity or antihypertensive effect of trandolapril

Zhu

Langaee

Gong

et al. 2016

Eur J Clin Pharmacol

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Purpose The majority of angiotensin-converting enzyme inhibitors (ACEIs) are synthesized as ester prodrugs that must be converted to their active forms in vivo in order to exert therapeutic effects. Hepatic carboxylesterase 1 (CES1) is the primary enzyme responsible for the bioactivation of ACEI prodrugs in humans. The genetic variant −816A>C (rs3785161) is a common variant located in the promoter region of the CES1P1 gene. Previous studies report conflicting results with regard to the association of this variant and therapeutic outcomes of CES1 substrate drugs. The purpose of this study was to determine the effect of the variant −816A>C on the activation of the ACEI prodrug trandolapril and the blood pressure (BP) lowering effect of trandolapril in hypertensive patients. Methods The −816A>C genotypes and CES1 expression and activity on trandolapril activation were determined in 100 individual human liver samples. Furthermore, the association of the −816A>C variant and the BP lowering effect of trandolapril was evaluated in hypertensive patients who participated in the INternational VErapamil SR Trandolapril Study (INVEST). Results Our in vitro study demonstrated that hepatic CES1 expression and activity did not differ among different −816A>C genotypes. Moreover, we were unable to identify a clinical association between BP lowering effects of trandolapril and −816A>C genotypes. Conclusions We conclude that the −816A>C variant is not associated with interindividual variability in CES1 expression, activity or therapeutic response to ACEI prodrugs.

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Section: Methodsmentioning

confidence: 99%

CES1P1 variant −816A>C is not associated with hepatic carboxylesterase 1 expression and activity or antihypertensive effect of trandolapril

Zhu

Langaee

Gong

et al. 2016

Eur J Clin Pharmacol

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“…Le bilan biologique d'entrée révélait la présence d'une acidose (pH 7,17, valeurs normales (7,45)) lactique (lactate à 4,9 mmol/L (0,5-2)), d'une hyperkaliémie à 5,9 mmol/L (3,5) …”

Section: Observationunclassified

“…Après contact avec le laboratoire fabriquant, le dosage de ce médicament se fait par immuno-histochimie. Une méthode de dosage par CLHP-SM/SM a été initiée [3] mais son intérêt demeurait limité du fait d'un stockage important de ce médicament dans les tissus. Ainsi, la quantification sérique n'a pas été réalisée.…”

Section: Résultatsunclassified

Intoxication volontaire au vérapamil et au bisoprolol : à propos d’un cas

et al. 2012

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Résumé -Objectif : Le traitement de l'hypertension artérielle primaire fait appel à différents médicaments cardiotropes aux effets toxiques comparables. Notre travail relate, chez un patient traité pour hypertension, une double intoxication au vérapamil et au bisoprolol initialement étiquetée bisoprolol seul, lors d'un premier screening toxicologique large. Matériel et méthodes : Le diagnostic de cette intoxication a été obtenu par la répétition de recherches larges par une méthode CLHP/UV/BD. Résultats : La découverte de l'intoxication double au bisoprolol et au vérapamil a été permise grâce à deux screening toxicologiques successifs. Les concentrations toxiques de vérapamil sont apparues après la décroissance des concentrations toxiques de bisoprolol, expliquant la persistance, dans le temps, des symptômes cardiovasculaires. Cette intoxication a conduit le patient à séjourner en service de réanimation médicale pendant plusieurs jours. Les concentrations de vérapamil sont restées toxiques pendant 6 jours. Conclusion : Devant l'absence de modification des signes cliniques et la présence de forme galénique à libération prolongée, la répétition d'un screening toxicologique large plutôt qu'un dosage spécifique du toxique initialement suspecté, a permis le dépistage et le suivi d'une intoxication poly-médicamenteuse à molécules cardiotropes. Mots clés : Vérapamil, bisoprolol, intoxication, CLHPAbstract -Objective: Primary essential high blood pressure is treated by different cardiotropic drugs which have similar toxicological effects. Our study is about a verapamil and bisoprolol poisoning, which was at first labelled as bisoprolol only, after a comprehensive toxicological analysis. Materials and methods: This poisoning was diagnosed by repeated HPLC/UV/DAD screenings. Results: Two successive screenings showed both verapamil and bisoprolol poisoning. Verapamil toxic concentrations were revealed after the decrease in bisoprolol concentrations, explaining the persistence in time of cardiovascular symptoms. The patient stayed for several days in an intensive care unit. Verapamil concentrations remained at a toxic level for six days. Conclusion: Because of the presence of sustained-release forms and unchanged clinical signs, repeating a comprehensive toxicological screening, instead of monitoring the initially suspected drug, helped in the screening and the follow-up of this multiple cardiotopic drug poisoning.

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“…Also there is a method reported in the literature to measure trandolapril in human plasma by tandem mass spectrometry [18]. The method was successfully applied for quantification of trandolapril and its metabolite trandolaprilat in human plasma by liquid chromatography/tandem mass spectrometry using solid-phase extraction [19]. Mass spectral fragmentation reactions of ACE inhibitors [20] and a study on the stereochemical purity of trandolapril were also reported [21].…”

Section: Introductionmentioning

confidence: 98%

“…A number of high performance liquid chromatography (HPLC) [19][20][21] and mass spectrometry analysis methods have been reported for this drug. However, the study of degradation behavior of trandolapril by UPLC under various ICH prescribed stress conditions has been lacking.…”

Section: Introductionmentioning

confidence: 99%

A Validated UPLC Method Used for the Determination of Trandolapril and its Degradation Products as per ICH Guidelines

Sahu¹,

Karthikeyan²,

Moorthy³

et al. 2011

CPA

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In this present research work, a new stability indicating assay method was developed for the estimation of trandolapril and its degraded products by isocratic reversed phase chromatographic technique using ultra performance liquid chromatography. The Study involves a comprehensive stress testing of trandolapril which was carried out according to ICH guideline Q1A (R2). The drug was subjected to acid (0.1M HCl), neutral (water) and alkaline (0.1M NaOH) hydrolysis at 80ºC, as well as the drug was kept at room temperature with H 2 O 2 for oxidative decomposition. Photolysis was carried out by exposing this drug into sunlight (60,000-70,000 lux) for 2 days. Additionally, the solid drug was subjected to 50ºC for 60 days in a hot air oven for thermal degradation. The results reveal that the degradation products of this drug were found in alkaline medium, acidic conditions and also in neutral hydrolysis. Separation of this drug and its degradation products (from various stress conditions) was successfully achieved on a BEH (bridged ethylene hybrid) C18 column utilizing water-acetonitrile in the ratio of 20:80. The flow rate and the detection wavelength for the analysis were 0.2 mL/min and 215 nm, respectively. The method was validated and the response was found to be linear in this drug concentration range of 0.431-2.155 M/mL (10-50 g/mL). The mean values (± %RSD) of slope, intercept and correlation coefficient were 2674262 (±0.9), 14924 (±1.02) and 0.9999 (±0.08), respectively. The %RSD values for intra-and inter-day precision studies were <1% and <2%, respectively. The recovery of this drug ranged between 98.93-100.18% from a mixture of degradation products. The obtained results reveal that the developed method is specific to this drug and selective to the degradation products.

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Quantification of trandolapril and its metabolite trandolaprilat in human plasma by liquid chromatography/tandem mass spectrometry using solid‐phase extraction

Cited by 12 publications

References 12 publications

CES1P1 variant −816A>C is not associated with hepatic carboxylesterase 1 expression and activity or antihypertensive effect of trandolapril

CES1P1 variant −816A>C is not associated with hepatic carboxylesterase 1 expression and activity or antihypertensive effect of trandolapril

Intoxication volontaire au vérapamil et au bisoprolol : à propos d’un cas

A Validated UPLC Method Used for the Determination of Trandolapril and its Degradation Products as per ICH Guidelines

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