scholarly journals Investigation of In Vivo and In Vitro Pharmacokinetic Characteristics of Kaji-ichigoside F1 in Rats

2020 ◽  
Vol 15 (3) ◽  
pp. 1934578X2091501
Author(s):  
Wenjuan Cui ◽  
Xiaoguang Fan ◽  
Naizhi Wang ◽  
Zhikun Zhang ◽  
Zhaolong Zhang ◽  
...  
Keyword(s):  
High Performance ◽  
Single Step ◽  
Selected Reaction Monitoring ◽  
Pharmacokinetic Studies ◽  
Triterpenoid Saponin ◽  
Pentacyclic Triterpenoid ◽  
Validation Parameters ◽  
Liquid Chromatography Tandem Mass

Kaji-ichigoside F1, a pentacyclic triterpenoid saponin, exhibits various beneficial pharmacological effects. In this study, a simple, rapid, and specific high-performance liquid chromatography-tandem mass spectrometry method for rapid quantification of kaji-ichigoside F1 in rat biological matrix was developed. Plasma was prepared by a single-step protein precipitation followed by separation of the analyte using an Inertsil ODS-3 column with a gradient mobile phase. Positive ion electrospray was used and selected reaction monitoring transitions were m/ z 673.27 → 511.15 for kaji-ichigoside F1 and m/ z 429.19 → 267.29 for morroniside, respectively. The developed method was validated with linear range of 20 to 10 000 ng/mL. All validation parameters were well within the acceptance limit based on the guidance of FDA. The validated method was successfully applied to analyze samples from the in vivo and in vitro pharmacokinetic studies in rats.

scholarly journals High-Performance Liquid Chromatography-Tandem Mass Spectrometry for Buprenorphine Evaluation in Plasma—Application to Pharmacokinetic Studies in Rabbits

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 437
Author(s):  
Marta Tikhomirov ◽  
Błażej Poźniak ◽  
Tomasz Śniegocki
Keyword(s):  
High Performance ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Studies ◽  
Limit Of Quantification ◽  
Reliable Determination ◽  
Main Challenge ◽  
Analytical Protocol ◽  
Liquid Chromatography Tandem Mass ◽  
Cost Efficient

The precise and reliable determination of buprenorphine concentration is fundamental in certain medical or research applications, particularly in pharmacokinetic studies of this opioid. The main challenge is, however, the development of an analytical method that is sensitive enough, as the detected in vivo concentrations often fall in very low ranges. Thus, in this study we aimed at developing a sensitive, repeatable, cost-efficient, and easy HPLC analytical protocol for buprenorphine in rabbit plasma. In order to obtain this, the HPLC-MS2 system was used to elaborate and validate the method for samples purified with liquid-liquid extraction. Fragment ions 468.6→396.2 and 468.6→414.2 were monitored, and the method resulted in a high repeatability and reproducibility and a limit of quantification of 0.25 µg/L with a recovery of 98.7–109.0%. The method was linear in a range of 0.25–2000 µg/L. The suitability of the analytical procedure was tested in rabbits in a pilot pharmacokinetic study, and it was revealed that the method was suitable for comprehensively describing the pharmacokinetic profile after buprenorphine intravenous administration at a dose of 300 µg/kg. Thus, the method suitability for pharmacokinetic application was confirmed by both the good validation results of the method and successful in vivo tests in rabbits.

Integrated UPLC-MS/MS and UHPLC-Q-Orbitrap HRMS Analysis to Reveal Pharmacokinetics and Metabolism of Five Terpenoids from Alpiniae Oxyphyllae Fructus in rats

2020 ◽  
Vol 21 ◽  
Author(s):  
Lihua Zuo ◽  
Jia Li ◽  
Lianping Xue ◽  
Qingquan Jia ◽  
Zhuolun Li ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Pharmacological Study ◽  
Pharmacokinetic Analysis ◽  
Validation Parameters ◽  
Liquid Chromatography Tandem Mass ◽  
Q Exactive

Background: Alpiniae oxyphyllae Fructus (AOF), as a traditional Chinese medicine (TCM), is widely used in the treatment of urinary, gastrointestinal and neurologic diseases in China. Although terpenoids are the main active ingredients of AOF, there are few researches on their pharmacokinetics and metabolism. Methods: In this study, a sensitive, rapid, accurate and novel ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to evaluate the pharmacokinetic behavior of five terpenoids (oxyphyllenodiol B, (4S*,5E,10R*)-7-oxo-tri-nor-eudesm-5-en-4β-ol, 7-epi-teucrenone, (+)-(4R,5S,7R)-13- hydroxynootkatone, (E)-labda-12,14-dien-15(16)-olide-17-oic acid) in rats after oral administration of AOF extracts. And 27 metabolic metabolites of the five terpenoids were identified by ultra high performance liquid chromatography -Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) based on precise mass and fragment ions. Results: The established pharmacokinetic analysis method showed good linearity over a wide concentration range, and the lower quantitative limit (LLOQ) were ranged from 0.97 to 4.25 ng/mL. And other validation parameters were within the acceptable range. In addition, 27 metabolites were identified in plasma, urine and feces samples, and the metabolic pathways of five terpenoids were mainly focus on glucoside conjugation, dehydration, desaturation and glycine conjugation. Conclusion: This is the first study on the pharmacokinetics and metabolism of five terpenoids in AOF at the same time, illuminating the disposal process of terpenoids in vivo. It was expected that the results of this study would provide some references for the apprehension of the action mechanism and the further pharmacological study of five terpenoids in AOF.

scholarly journals Implication of Opioid Receptors in the Antihypertensive Effect of a Novel Chicken Foot-Derived Peptide

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 992
Author(s):  
Anna Mas-Capdevila ◽  
Lisard Iglesias-Carres ◽  
Anna Arola-Arnal ◽  
Gerard Aragonès ◽  
Begoña Muguerza ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Opioid Receptors ◽  
High Performance ◽  
Antihypertensive Effect ◽  
High Resolution Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

The peptide AVFQHNCQE demonstrated to produce nitric oxide-mediated antihypertensive effect. This study investigates the bioavailability and the opioid-like activity of this peptide after its oral administration. For this purpose, in silico and in vitro approaches were used to study the peptide susceptibility to GI digestion. In addition, AVFQHNCQE absorption was studied both in vitro by using Caco-2 cell monolayers and in vivo evaluating peptide presence in plasma from Wistar rats by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and by ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Both in vivo and in vitro experiments demonstrated that peptide AVFQHNCQE was not absorbed. Thus, the potential involvement of opioid receptors in the BP-lowering effect of AVFQHNCQE was studied in the presence of opioid receptors-antagonist Naloxone. No changes in blood pressure were recorded in rats administered Naloxone, demonstrating that AVFQHNCQE antihypertensive effect is mediated through its interaction with opioid receptors. AVFQHNCQE opioid-like activity would clarify the antihypertensive properties of AVFQHNCQE despite its lack of absorption.

scholarly journals Metabolite identification, tissue distribution, excretion and preclinical pharmacokinetic studies of ET-26-HCl, a new analogue of etomidate

2020 ◽  
Vol 7 (2) ◽  
pp. 191666
Author(s):  
Lu Yu ◽  
Xu Chen ◽  
Wen Sheng Zhang ◽  
Liang Zheng ◽  
Wen Wen Xu ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Intravenous Administration ◽  
High Performance ◽  
Anaesthetic Agent ◽  
Parent Compound ◽  
Liver Microsomes ◽  
Metabolite Identification ◽  
Pharmacokinetic Studies

ET-26-HCl, a novel anaesthetic agent with promising pharmacological properties, lacks extensive studies on pharmacokinetics and disposition in vitro and in vivo . In this study, we investigated the metabolic stability, metabolite production and plasma protein binding (PPB) of ET-26-HCl along with its tissue distribution, excretion and pharmacokinetics in animals after intravenous administration. Ultra-high performance liquid chromatography–tandem quadrupole time-of-flight mass spectrometry identified a total of eight new metabolites after ET-26-HCl biotransformation in liver microsomes from different species. A hypothetical cytochrome P450-metabolic pathway including dehydrogenation, hydroxylation and demethylation was proposed. The PPB rate was highest in mouse and lowest in human. After intravenous administration, ET-26-HCl distributed rapidly to all tissues in rats and beagle dogs, with the highest concentrations in fat and liver. High concentrations of ET-26-acid, a major hydroxylation metabolite of ET-26-HCl, were found in liver, plasma and kidney. Almost complete clearance of ET-26-HCl from plasma occurred within 4 h after administration. Only a small fraction of the parent compound and its acid form were excreted via the urine and faeces. Taken together, the results added to a better understanding of the metabolic and pharmacokinetic properties of ET-26-HCl, which may contribute to the further development of this drug.

scholarly journals Comparative Studies on Multi-Component Pharmacokinetics of Polygonum multiflorum Thunb Extract After Oral Administration in Different Rat Models

2021 ◽  
Vol 12 ◽  
Author(s):  
Ninghui Ma ◽  
Yong Zhang ◽  
Liyan Sun ◽  
Yuan Zhao ◽  
Yue Ding ◽  
...  
Keyword(s):  
Phase Ii ◽  
High Performance ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Polygonum Multiflorum ◽  
Liquid Chromatography Tandem Mass ◽  
Aloe Emodin ◽  
Main Basis ◽  
Phase Ii Metabolites

The clinical use of Polygonum multiflorum Thunb (PM) has been restricted or banned in many countries, due to its hepatotoxic adverse effects. Its toxicity research has become a hot topic. So far, the pharmacokinetic studies of PM, focusing on prototype compounds such as 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), emodin, and physcion, have been considered the main basis of pharmacodynamic material or of toxic effect. However, pharmacokinetic studies of its phase II metabolites have not yet been reported, mainly because the quantifications of such metabolites are difficult to do without the reference substance. In addition, pharmacokinetic studies on different pathological models treated with PM have also not been reported. On the other hand, toxic effects of PM have been reported in patients diagnosed with different liver pathologies. In the present work, a simultaneous quantitation method for eight prototypes components of PM and their five phase II metabolites has been performed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and used for the pharmacokinetic study of PM in two different liver pathological models in rats (normal, alpha-naphthylisothiocyanate (ANIT), and carbon tetrachloride (CCl4)). The results showed that the main blood-entering components of PM are TSG, emodin, physcion, emodin-8-O-β⁃D⁃glucoside (E-Glu), physcion-8-O-β⁃D⁃glucoside (P-Glu), aloe-emodin, gallic acid, resveratrol and catechin, among which TSG, emodin, and catechin were primary metabolized in phase II, while resveratrol was converted to all phase II metabolites, and the others were metabolized as drug prototypes. Meanwhile, their pharmacokinetic parameters in the different models also exhibited significant differences. For instance, the AUC (0-∞) values of the TSG prototype and its phase II metabolites were higher in the ANIT group, followed by CCl4 group and the normal group, while the AUC (0-∞) values of the emodin prototype and its phase II metabolites were higher in the CCl4 group. To further illustrate the reasons for the pharmacokinetic differences, bilirubin metabolizing enzymes and transporters in the liver were measured, and the correlations with the AUC of the main compounds were analyzed. TSG and aloe-emodin have significant negative correlations with UGT1A1, BSEP, OATP1A4, OCT1, NTCP, MRP2 and MDR1 (p < 0.01). These data suggest that when the expression of metabolic enzymes and transporters in the liver is inhibited, the exposure levels of some components of PM might be promoted in vivo.

scholarly journals Biodistribution and Anticancer Characteristics of Les-3833, A Novel 4-thiazolidinone-Based Lead Compound

2020 ◽  
Vol 88 (2) ◽  
pp. 18 ◽  
Author(s):  
Lesya Kobylinska ◽  
Andrii Lozynskii ◽  
Roman Lesyk ◽  
Rostyslav Stoika ◽  
Sandor G. Vari
Keyword(s):  
Maximum Concentration ◽  
High Performance ◽  
Maximum Level ◽  
Lead Compound ◽  
Short Period ◽  
Liquid Chromatography Tandem Mass ◽  
Liver And Kidney ◽  
The Brain

Recently, we identified the promising anticancer potential of the synthetic 4-thiazolidinone-based anticancer lead compound Les-3833 which demonstrated tumor-suppressing action in vitro and in vivo. Based on the results of previous studies, the aim of this research was to investigate the cytotoxicity in vitro and the biodistribution in laboratory mice to support the biotherapeutic drug development of Les-3833. Les-3833 (2.5 mg/kg) was intravenously injected into male Balb/c mice. Measurements were performed at 5 min, 15 min, 1 h, 4 h, and 24 h time points in blood plasma, brain, liver, and kidney using high-performance liquid chromatography/tandem mass spectrometry. After the administration of Les-3833, the maximum level of this compound was observed in plasma at 2.08 min. In the brain, the mean maximum concentration of Les-3833 was 7.17 ng/mL at 5 min, while after 15 min, it was not found. In the liver, at 5 min, the maximum concentration was 1190 ng/g. At 15 min, concentration of Les-3833 in the liver decreased by 14.3%; at 6 h by 22.8%; and after 24 h by 64.7%. Its maximum concentration in kidney was 404 ng/g within 5–15 min, at 1 h it decreased by 36.1%, and after 24 h by 49.3%. Thus, Les-3833 was rapidly taken up by different organs from the bloodstream, partially metabolized in the liver, and excreted mainly through the kidneys, while in the brain, a very low concentration could be observed for only a short period of time.

scholarly journals CREATING A PROLONGED FORM OF ACETYLSALICYLIC ACID: AN EXPERIMENTAL APPROACH

2016 ◽  
Vol 18 (1) ◽  
pp. 22-31
Author(s):  
V. I. Sevastianov ◽  
V. K. Popov ◽  
V. Yu. Belov ◽  
S. V. Kursakov ◽  
E. N. Antonov ◽  
...  
Keyword(s):  
Acetylsalicylic Acid ◽  
Blood Plasma ◽  
High Performance ◽  
Release Kinetics ◽  
High Performance Liquid Chromatographic ◽  
Model Solution ◽  
Pharmacokinetic Studies ◽  
Highly Porous

Aim.The development of a prolonged form of acetylsalicylic acid (ASA) encapsulated into polymeric highly porous microcarriers using supercritical carbon dioxide and the subsequent study of ASA release kinetics in vitro and in vivo using high-performance liquid chromatographic (HPLC).Materials and methods.As polymeric carriers for ASA encapsulation amorphous D,L-polylactides (PLA) and polylactoglycolides (PLGA) of PURASORB PDL02 and PDLG7502 series (PURAC Biochem BV, Netherlands) were selected. The ASA encapsulation was performed using the PGSS (Particles from Gas Saturated Solutions) method of supercritical fl uid formation of microfi ne (20–50 μm) bioresorbable powders of aliphatic polyethers containing 10 wt.% ASA. The release kinetics of ASA from polymeric microparticles into saline solution as well as pharmacokinetic studies in vivo (rabbits) were registered by HPLC.Results.A method of quantitative determination of ASA and its main metabolite salicylic acid (SA) in model solution and blood plasma by HPLC-UV detection with enhanced sample preparation and selectivity was developed. The method’s analytical range without accounting for dilution was 0.05–5.0 μg/ml for model solution and 0.2–10.0 μg/ml for blood plasma; the degree of extraction of ASA SA from blood plasma – 95.8 and 98.1%, respectively. It was demonstrated that the amount of ASA released from PLA during the fi rst 4 h exceeds the mass of ASA released from PLGA by approximately 25% which may serve as a justifi cation for the selection of PLGA as a carrier for the creation of a prolonged form of ASA. Pharmacokinetic studies (rabbits, n = 3) demonstrated a gradual release of ASA from PLGA microparticles during 24 h after intramuscular implantation of encapsulated form of ASA at the dose of 10 mg/kg.Conclusion.Test samples of highly porous microfi ne powders of PLGA obtained by PGSS containing up to 10 wt.% ASA may serve as source prototypes for the development and creation on their basis of a prolonged form of ASA.

scholarly journals Simultaneous determination of calycosin, prim-O-glucosylcimifugin, and paeoniflorin in rat plasma by HPLC-MS/MS: application in the pharmacokinetic analysis of HQCF

2020 ◽  
Vol 48 (11) ◽  
pp. 030006052097290
Author(s):  
Yulong Gu ◽  
Xianglan Piao ◽  
Dan Zhu
Keyword(s):  
Formic Acid ◽  
High Performance ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Selected Reaction Monitoring ◽  
Pharmacokinetic Analysis ◽  
Ionization Source ◽  
Liquid Chromatography Tandem Mass

Objective This study aimed to develop and validate a high-performance liquid chromatography–tandem mass spectrometry method to simultaneously determine three bioactive components of the Huangqi Chifeng decoction (HQCF) in rat plasma. Methods Taxol was used as an internal standard in the developed method. Chromatographic separation was performed on a C18 column using a gradient elution with 0.1% formic acid in acetonitrile (v/v) and 0.1% formic acid in water (v/v) as the mobile phases at a flow rate of 0.4 mL·minute−1. All compounds were monitored via selected reaction monitoring with an electrospray ionization source. Results The lower limits of quantification of paeoniflorin, calycosin, and prim- O-glucosylcimifugin were 15.0, 0.75, and 0.75 ng·mL−1, respectively. The calibration curves indicated optimal linearity ( r > 0.99) across the concentration ranges. The specificity, precision, accuracy, recovery, matrix effect, and stability of the method were validated. This method was successfully applied in a pharmacokinetics study of the three compounds in rat plasma. Conclusion The pharmacokinetics results provide insights into the mechanisms of HQCF in vivo and its future clinical application.

PTCA (1-H-Pyrrole-2,3,5-Tricarboxylic Acid) as a Marker for Oxidative Hair Treatment: Distribution, Gender Aspects, Correlation with EtG and Self-Reports

2020 ◽  
Author(s):  
Sara Casati ◽  
Alessandro Ravelli ◽  
Ilaria Angeli ◽  
Roberta F Bergamaschi ◽  
Giorgio Binelli ◽  
...  
Keyword(s):  
High Performance ◽  
Hair Analysis ◽  
False Negative ◽  
Tricarboxylic Acid ◽  
Single Step ◽  
Ethyl Glucuronide ◽  
Hair Samples

Abstract Hair analysis is an important and reliable resource for the assessment of alcohol or drug abstinence in both clinical and forensic toxicology. Recently, it has been demonstrated that hair oxidative cosmetic treatments lead to the reduction in incorporated xenobiotics in hair, such as ethyl glucuronide (EtG), a marker of alcohol abuse, and the formation of 1-H-pyrrole-2,3,5-tricarboxylic acid (PTCA), a degradation product of melanin. The aim of the present study was to investigate PTCA trends in a large number of samples in order to evaluate the reliability of this biomarker in recognizing previous cosmetic treatment in forensic analyses. Therefore, a single-step extraction followed by an high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) method was established and validated for the simultaneous determination of EtG and PTCA. This method was applied to 1,219 scalp hair samples from two groups, namely self-reported untreated and in vivo treated hair, exhibiting a concentration range of 6.7 to 440.0 pg/mg for EtG (mean 26.8 pg/mg, median 14.6 pg/mg) and 0.009 to 49.8 ng/mg for PTCA (mean 0.66 ng/mg, median 0.02 ng/mg). The PTCA content was significantly different among the two experimental groups, with the in vivo treated group showing significantly higher levels of PTCA than the untreated group. Finally, an in vitro bleaching was performed and the results confirmed that a strong hair oxidative treatment may negatively affect EtG test results (false negative), whereas the mean PTCA content increased showing statistically significant differences between untreated and in vitro oxidative treated samples. The present study suggests that the determination of PTCA in routine hair analysis procedure could be useful in order to discover previous cosmetic treatment including oxidation.

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