HPLC–MS/MS method for the simultaneous quantification of desmethylmebeverine acid, mebeverine acid and mebeverine alcohol in human plasma along with its application to a pharmacokinetics study

Moskaleva, Natalia E.; Baranov, Pavel A.; Mesonzhnik, Natalia V.; Appolonova, Svetlana A.

doi:10.1016/j.jpba.2017.02.006

Cited by 9 publications

(7 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Any new aspect of the knowledge of pharmacokinetics and metabolomics of SCs may serve for a better understanding of the clinical and toxicological findings attributable to drug poisoning and misuse cases [ 12 ]. Mass spectrometric approaches are commonly used in the study of endogenous compounds [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Properties of the Novel Synthetic Cannabinoid 5F-APINAC and Its Influence on Metabolites Associated with Neurotransmission in Rabbit Plasma

et al. 2021

Self Cite

View full text Add to dashboard Cite

The strong psychoactive effects of synthetic cannabinoids raise the need for the deeper studying of their neurometabolic effects. The pharmacokinetic properties of 5F-APINAC and its influence on metabolomics profiles associated with neurotransmission were investigated in rabbit plasma. Twelve rabbits divided into three groups received 1-mL 5F-APINAC at 0.1, 1 and 2 mg/kg. The intervention groups were compared with the controls. Sampling was performed at nine time points (0–24 h). Ultra-high-performance liquid chromatography–tandem mass spectrometry was used. The pharmacokinetics were dose-dependent (higher curve at a higher dose) with a rapid biotransformation, followed by gradual elimination within 24 h. The tryptophan concentrations abruptly decreased (p < 0.05) in all tested groups, returning to the basal levels after 6 h. 5-hydroxylindole acetic acid increased (p < 0.05) in the controls, but this trend was absent in the treated groups. The aspartic acid concentrations were elevated (p < 0.001) in the treated groups. L-kynurenine was elevated (p < 0.01) in the intervention groups receiving 1 mg/kg to 2 mg/kg. Dose-dependent elevations (p < 0.01) were found for kynurenic acid, xanthurenic acid and quinolinic acid (p < 0.01), whereas the anthranilic acid trends were decreased (p < 0.01). The indole-3-propionic acid and indole-3-carboxaldehyde trends were elevated (p < 0.05), whereas the indole-3-lactic acid trajectories were decreased (p < 0.01) in the intervention groups. 5F-APINAC administration had a rapid biotransformation and gradual elimination. The metabolites related to the kynurenine and serotonergic system/serotonin pathways, aspartic acid innervation system and microbial tryptophan catabolism were altered.

show abstract

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Properties of the Novel Synthetic Cannabinoid 5F-APINAC and Its Influence on Metabolites Associated with Neurotransmission in Rabbit Plasma

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…A variety of analytical methods have been reported to determine teriflunomide in different biological matrices (Dias et al, 1995;Moskaleva et al, 2017;Li et al, 2002;van Roon et al, 2004;Schmidt et al, 2003). Most sample preparation methods are based on liquid-liquid extraction of teriflunomide from the biological matrix with following evaporation of organic phase and its reconstitution in the mobile phase or suitable solvent.…”

Section: Figure 1 Chemical Structure Of Teriflunomide and Leflunomidementioning

confidence: 99%

Determination of Teriflunomide Across a Wide Dynamic Concentration Range in Human Plasma by Lc–ms/MS

Moskaleva¹,

Mesonzhnik²,

Kuznetsov³

et al. 2019

PTQ

Self Cite

View full text Add to dashboard Cite

Leflunomide is an antirheumatic drug with anti-inflammatory and antirheumatic properties, it is rapidly metabolized in the body to the active metabolite teriflunomide, which causes its pharmacological activity. At the usual 20-mg daily dosage of leflunomide, the expected teriflunomide plasma concentration is about 35 μg/ml. The pharmacokinetics of the drug is characterized by a large interindividual variability and a long half-life, which in combination with possible side effects creates the need to control the concentration of teriflunomide in the blood plasma. Teriflunomide may increase the risk of fetal death or teratogenic effects when administered to pregnant women. Teriflunomide plasma concentrations less than 0.02 μg/ml are preferred for patients anticipating pregnancy. In this study, a sensitive and high-performance method for analyzing teriflunomide in human blood plasma in a wide range of concentrations was developed and validated using a triple quadrupole liquid chromatography-mass spectrometer (HPLC-MS/MS). Sample preparation was performed by protein precipitation with acetonitrile, followed by chromatographic separation using an Acquity UPLC BEN C8 1.7 mm, 2.1 × 50 mm column (Waters, USA). D4-teriflunomide was used as an internal standard. The developed method was validated in the concentration range from 0.001 μg/ml to 200 μg/ml teriflunomide in plasma. Accuracy (%), defined as the difference between the nominal and measured concentration and reproducibility (coefficient of variation CV) ranged from -5.02% to 5.00% and from 0.47% to 9.30%, respectively, within the series and between series of samples. The developed method was successfully used to analyze volunteer blood plasma samples after taking 20 mg of leflunomide.

show abstract

“…After oral administration, MEB is rapidly and completely metabolized to mebeverine alcohol and veratric acid. Moreover, as a result of MEB hydrolysis and desmethylation steps, mebeverine acid and desmethylmebeverine acid are the major metabolites of MEB found in real human samples [20,21]. Due to its vital importance, MEB quantification in dosage forms and biological fluids at low concentrations is of great importance.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, most of these methods have been applied for the MEB quantification in dosage forms and spiked biological samples. The literature survey reveals several analytical methods for MEB quantification, such as chromatographic [21,22], GC-MS [23], spectrophotometric [24,25], spectrofluorometric [25,26] and electrochemical methods [27][28][29][30][31][32][33]. Carbon paste electrodes (CPEs) have been applied successfully for MEB quantification either using potentiometric [31] or voltametric techniques [32,33].…”

Section: Introductionmentioning

confidence: 99%

Graphite Studded with Facile-Synthesized Cu2O Nanoparticle-Based Cubes as a Novel Electrochemical Sensor for Highly Sensitive Voltametric Determination of Mebeverine Hydrochloride

et al. 2021

View full text Add to dashboard Cite

Herein, a feasible chemical reduction method followed by intensive mixing was applied for the preparation of an attractive material based on graphite studded with cuprous oxide nanoparticle-based cubes (Cu2ONPs–C@G). Transmission electron microscope (TEM), scanning electron microscope (SEM), X-ray diffraction (XRD) and cyclic voltammetry (CV) were utilized for characterization. Cuprous oxide nanoparticles (Cu2ONPs), with a diameter range mainly distributed from 4 to 20 nm, aggregate to form microcubes (Cu2ONPs–C) with an average diameter of about 367 nm. Paste electrode was prepared using Cu2ONPs–C@G (Cu2ONPs–C@G/PE) for voltametric quantification of the musculotropic antispasmodic drug: mebeverine hydrochloride (MEB). The electrochemical behavior of MEB was studied using CV, and the optimum analytical parameters were investigated using square wave adsorptive anodic stripping voltammetry (SWAdASV). Moreover, density functional theory (DFT) was used to emphasize the ability of MEB to form a complex with Cu2+, confirming the suggested electrochemical behavior of MEB at Cu2ONPs–C@G/PE. With good stability and high reproducibility, SWAdASV of Cu2ONPs–C@G/PE shows successful quantification of MEB over the concentration range of 5.00 × 10−11–1.10 × 10−9 M with lower limit of detection (LOD) and lower limit of quantification (LOQ) values of 2.41 × 10−11 M and 8.05 × 10−11 M, respectively. Finally, accurate quantification of MEB in dosage forms (tablets) and biological fluids (spiked human urine and plasma samples) was achieved using Cu2ONPs-C@G/PE.

show abstract

HPLC–MS/MS method for the simultaneous quantification of desmethylmebeverine acid, mebeverine acid and mebeverine alcohol in human plasma along with its application to a pharmacokinetics study

Cited by 9 publications

References 10 publications

Pharmacokinetic Properties of the Novel Synthetic Cannabinoid 5F-APINAC and Its Influence on Metabolites Associated with Neurotransmission in Rabbit Plasma

Pharmacokinetic Properties of the Novel Synthetic Cannabinoid 5F-APINAC and Its Influence on Metabolites Associated with Neurotransmission in Rabbit Plasma

Determination of Teriflunomide Across a Wide Dynamic Concentration Range in Human Plasma by Lc–ms/MS

Graphite Studded with Facile-Synthesized Cu2O Nanoparticle-Based Cubes as a Novel Electrochemical Sensor for Highly Sensitive Voltametric Determination of Mebeverine Hydrochloride

Contact Info

Product

Resources

About