Simultaneous determination of clevidipine and its primary metabolite in dog plasma by liquid chromatography–tandem mass spectrometry: Application to pharmacokinetic study

Zhou, Ying; Li, Huqun; He, Xiaomeng; Jia, Mengmeng; Ni, Yang; Xu, Mingzhen; Chen, Hui; Li, Weiyong

doi:10.1016/j.jpba.2014.08.018

Cited by 5 publications

(12 citation statements)

References 18 publications

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“…The pharmacokinetic profiles in dog were closer to those in human so that the Beagle dogs were chosen as the experimental animals for pharmacokinetic study rather than rats. For example, following administration, clevidipine exhibits triphasic elimination with the initial phase accounting for the majority (approximately 85%-90%) of the area under the concentration-time curve irrespective of in human [11,15] or dogs. However, there are also some differences.…”

Section: Discussionmentioning

confidence: 99%

“…The supernatant (5 μL) was injected into the LC-MS/MS system using an autosampler. [15] An Agilent 1200 High Performance Liquid Chromatography System (Agilent, Germany) equipped with quaternary pump, degasser, autosampler and column oven was used in the study. The chromatographic separation was achieved on an Ultimate XB-C18 column (2.1×50 mm, 5 µm, Welch Materials Inc., China) under isocratic conditions with the mobile phase containing acetonitrile and 20 mmol/L ammonium acetate buffer (40:60, v/v) at the flow rate of 0.3 mL/min.…”

Section: Determination Of Clevidipine and H152/81 In Dog Plasma And Rmentioning

confidence: 99%

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Pharmacokinetics and tissue distribution of clevidipine and its metabolite in dogs and rats

Zhou

et al. 2014

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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The purpose of the current study was to examine the pharmacokinetic profiles and tissue distribution of clevidipine, an ultra-short-acting calcium antagonist in Beagle dogs and Sprague-Dawley rats, respectively. The pharmacokinetics and biodistribution of its primary metabolite H152/81 were also evaluated. Dogs received intravenous infusion of clevidipine at a dose rate of 17 μg/(kg·min), and rats were given intravenous administration of clevidipine at a dose of 5 mg/kg. Dog plasma and rat tissues were collected and assayed by HPLC-MS/MS. It was found that plasma clevidipine quickly reached the steady state concentration. The terminal half-life was short (16.8 min), pointing out a rapid elimination after the end of the infusion. The total clearance was 5 mL/(min·kg). In comparison, plasma concentration of H152/81 was increased more slowly and was significantly higher than that of clevidipine. After intravenous administration, clevidipine was distributed rapidly into all tissues examined, with the highest concentrations found in the brain, heart and liver. Maximal concentrations of clevidipine were found in most tissues at 10 min post-dosing. However, the proportion of clevidipine distributed in all tissues was quite small (0.042‰) compared to the total administration dose. It was suggested that clevidipine was mainly distributed in blood and it transformed to inactive metabolite rapidly.

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Section: Discussionmentioning

confidence: 99%

Section: Determination Of Clevidipine and H152/81 In Dog Plasma And Rmentioning

confidence: 99%

Pharmacokinetics and tissue distribution of clevidipine and its metabolite in dogs and rats

Zhou

et al. 2014

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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“…Due to the ultra-short elimination half-life, it is recommended to collect whole blood samples in tubes prefilled with esterase inhibitors to immediately stop the degradation of clevidipine to avoid underestimation of clevidipine and overestimation of its primary metabolite [13]. Thus, in this method, we determined the drug concentration in whole blood rather than plasma [14,15] using tubes prefilled with stabilizer cocktail.…”

Section: Stabilization Of Clevidipine In Dog Whole Bloodmentioning

confidence: 99%

“…Recently, two papers have been published to report PK study in beagle dogs. Zhou et al [14] reported a LC-MS/MS method for simultaneous determination of clevidipine and its major metabolite in dog plasma rather than whole blood using felodipine as internal standard. Nevertheless, the authors did not take extra measures to prevent clevidipine hydrolysis as well as its metabolite from further oxidation in blood except for lowering the temperature.…”

Section: Introductionmentioning

confidence: 99%

Screening of Stabilizers for LC–MS/MS Analysis of Clevidipine and its Primary Metabolite in Dog Whole Blood

et al. 2015

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“…Literature survey reveals determination of CLEVI and its metabolite by HPLC method [4]. LC-MS/MS methods are reported for determination of CLEVI [5][6][7]. Various methods are reported for determination of related substances of clevidipine butyrate by HPLC method [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Stability Indicating HPTLC Method for Determination of Clevidipine Butyrate in Synthetic Mixture

Pandya

Rajput

2018

Int J Pharm Pharm Sci

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Objective: To develop and validate stability indicating HPTLC method for determination of clevidipine butyrate in synthetic mixture. Methods:The present study deals with development and validation of stability indicating HPTLC method for estimation of clevidipine butryate. Chromatographic separation was performed on aluminum plate pre coated with Silica Gel 60 F254 using toluene: ethyl acetate (8:2) as mobile phase. TLC scanner was set at wavelength of 370 nm. Results: Retention factor RfConclusion: A new, Simple, Accurate, Precise, Sensitive and economic stability indicating HPTLC method has been developed and validated for the determination of clevidipine and can be employed for stability indicating analysis.of clevidipine was found to be 0.49. The method was validated as per ICH guidelines. Calibration curve was in the range of 1000-6000ng/band. The correlation coefficient was found to be 0.999. The precision expressed by RSD was less than 2%. The accuracy of method was confirmed by recovery studies using standard addition method and recovery was found to be 99.03-99.57%. The drug was subjected to ICH prescribed hydrolytic, oxidative, photolytic and thermal stress conditions. Clevidipine and its degradation products were well resolved under experimental conditions. The method was validated according to ICH guidelines. The drug showed significant degradation in alkaline and acidic condition and slight degradation in oxidative condition. The drug was stable in thermal condition.

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Simultaneous determination of clevidipine and its primary metabolite in dog plasma by liquid chromatography–tandem mass spectrometry: Application to pharmacokinetic study

Cited by 5 publications

References 18 publications

Pharmacokinetics and tissue distribution of clevidipine and its metabolite in dogs and rats

Pharmacokinetics and tissue distribution of clevidipine and its metabolite in dogs and rats

Screening of Stabilizers for LC–MS/MS Analysis of Clevidipine and its Primary Metabolite in Dog Whole Blood

Stability Indicating HPTLC Method for Determination of Clevidipine Butyrate in Synthetic Mixture

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