scholarly journals Stereo-Selective Pharmacokinetics of Ilimaquinone Epimers Extracted from a Marine Sponge in Rats

Marine Drugs ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 171 ◽  
Author(s):  
Heebin Son ◽  
Keumhan Noh ◽  
InWha Park ◽  
MinKyun Na ◽  
Sangtaek Oh ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Elimination Rate ◽  
Systemic Exposure ◽  
Rat Plasma ◽  
Absolute Bioavailability ◽  
Anti Cancer ◽  
The Stability ◽  
The Individual ◽  
Intravenous And Oral Administration

An ilimquinone (IQ) mixture isolated from Hippiospongia metachromia, consisting of IQ and epi-ilimaquinone (epi-IQ), exerts anti-HIV, anti-microbial, anti-inflammatory, and anti-cancer effects. An HPLC-MS/MS method was developed for simultaneous determination of the two epimers in rat plasma, separating them using a biphenyl column. Ascorbic acid is added during the sample preparation to ensure the stability of both isomers. The plasma concentrations of the isomers were monitored following intravenous and oral administration of the IQ mixture in rats as well as the individual epimers that were separately orally administered. Compare to IQ, epi-IQ was much more stable in rat plasma, likely due to its configurations of decalin. Both substances decayed in more than bi-exponential pattern, with an elimination rate constant of 1.2 h−1 for IQ and 1.7 h−1 for epi-IQ. The epi-IQ was distributed more widely than IQ by about two-fold. Consequently, the clearance of epi-IQ was greater than that of IQ by about three-fold. The oral absolute bioavailability for IQ was 38%, and, that for epi-IQ, was 13%. Although the systemic exposure of IQ was greater than that of epi-IQ by ~8.7-fold, the clearance of each isomer was similar when administered either orally or intravenously, when normalized for bioavailability. The stereo-specific behavior of the isomers appears to originate from differences in both their tissue distribution and gastrointestinal permeability.

Study on pharmacokinetics of nimodipine nano-controlled release agent modified by host-guest reaction of β-cyclodextrin in rats

2021 ◽  
Vol 11 (6) ◽  
pp. 839-845
Author(s):  
Xiaoxiu Fu ◽  
Lin Ma ◽  
Yang Cao ◽  
Hengzhong Xu ◽  
Yan Guo
Keyword(s):  
Controlled Release ◽  
The Elderly ◽  
Rat Plasma ◽  
Cerebrovascular Diseases ◽  
Absolute Bioavailability ◽  
Release Agent ◽  
Dihydropyridine Calcium Channel Antagonist ◽  
Oral Preparation ◽  
Ischemic Cerebrovascular Diseases ◽  
The Stability

Nimodipine (NIMO) has been identified as a second-generation dihydropyridine calcium channel antagonist. NIMO’s specificity for the cerebrovascular smooth muscle contributes to its broad usage in treating ischemic cerebrovascular diseases in the elderly. Therefore, enhancing NIMO’s therapeutic effect and reducing its adverse reactions caused by short-term repeated use have become a focus of research. As a result, a new controlled-release preparation of NIMO, the carboxymethyl chitosan/nimodipine-hydroxypropyl-β-cyclodextrin nanoparticle (Nano-NIMO), was constructed based on hydroxypropyl-β-cyclodextrin. The novel composite Nano-NIMO preparation could significantly improve the stability of NIMO in rat plasma, achieving an absolute bioavailability as high as 62.3%, which is three times that of the traditional NIMO oral preparation. Therefore, Nano-NIMO is expected to provide a new direction for the preparation of modified controlled-release Nano- NIMO agents.

scholarly journals Physicochemical Effects of the Major Quassinoids in a Standardized Eurycoma longifolia Extract (Fr 2) on the Bioavailability and Pharmacokinetic Properties, and their Implications for Oral Antimalarial Activity

2011 ◽  
Vol 6 (3) ◽  
pp. 1934578X1100600 ◽  
Author(s):  
Bin-Seng Low ◽  
Chin-Hoe Teh ◽  
Kah-Hay Yuen ◽  
Kit-Lam Chan
Keyword(s):  
Oral Administration ◽  
Intravenous Administration ◽  
Antimalarial Activity ◽  
Elimination Rate ◽  
Rat Plasma ◽  
Chemical Degradation ◽  
Absolute Bioavailability ◽  
Phytochemical Analysis ◽  
Eurycoma Longifolia ◽  
Pharmacokinetic Properties

A simple validated LC-UV method for the phytochemical analysis of four bioactive quassinoids, 13α(21)-epoxyeurycomanone (EP), eurycomanone (EN), 13α,21-dihydroeurycomanone (ED) and eurycomanol (EL) in rat plasma following oral (200 mg/kg) and intravenous administration (10 mg/kg) of a standardized extract Fr 2 of Eurycoma longifolia Jack was developed for pharmacokinetic and bioavailability studies. The extract Fr 2 contained 4.0%, 18.5%, 0.7% and 9.5% of EP, EN, ED and EL, respectively. Following intravenous administration, EP displayed a relatively longer biological half-life (t½ = 0.75 ± 0.25 h) due primarily to its lower elimination rate constant (ke) of 0.84 ± 0.26 h−1) when compared with the t½ of 0.35 ± 0.04 h and ke of 2.14 ± 0.27 h−1, respectively of EN. Following oral administration, EP showed a higher Cmax of 1.61± 0.41 μg/mL over that of EN (Cmax = 0.53 ± 0.10 μg/mL). The absolute bioavailability of EP was 9.5-fold higher than that of EN, not because of chemical degradation since both quassinoids were stable at the simulated gastric pH of 1. Instead, the higher log Kow value of EP (-0.43) contributed to greater membrane permeability over that of EN (log Kow = −1.46) at pH 1. In contrast, EL, being in higher concentration in the extract than EP, was not detected in the plasma after oral administration because of substantial degradation by the gastric juices after 2 h. Similarly, ED, being unstable at the acidic pH and together with its low concentration in Fr 2, was not detectable in the rat plasma. In conclusion, upon oral administration of the bioactive standardized extract Fr 2, EP and EN may be the only quassinoids contributing to the overall antimalarial activity; this is worthy of further investigation.

scholarly journals Pharmacokinetic UPLC–MS/MS studies on byakangelicol after oral and intravenous administration to rats

2020 ◽  
Vol 32 (1) ◽  
pp. 49-52
Author(s):  
Xi Bao ◽  
Bingge Huang ◽  
Yiting Mao ◽  
Zhiguang Zhang ◽  
Yunfang Zhou ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Multiple Reaction Monitoring ◽  
A549 Cells ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Absolute Bioavailability ◽  
Dependent Manner ◽  
Limit Of Quantitation ◽  
Intravenous And Oral Administration

Byakangelicol is one of coumarins from Baizhi and has been shown to inhibit the release of PGE2 from human lung epithelial A549 cells in a dose-dependent manner. A sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and full validated for the quantification of byakangelicol in rat plasma. The pharmacokinetics of byakangelicol after both intravenous (5 mg/kg) and oral (15 mg/kg) administrations were studied. Chromatographic separation was performed on an ultra-performance liquid chromatography ethylene bridged hybrid (UPLC BEH) C18 column with acetonitrile and 0.1% formic acid as the mobile phase at a flow rate of 0.4 mL/min; fargesin was used as the internal standard (IS). The following quantitative analysis of byakangelicol was utilized in the multiple reaction monitoring mode. The samples were extracted from rat plasma via protein precipitation using acetonitrile. In the concentration range of 1–2000 ng/mL, the method correlated linearity (r > 0.995) with a lower limit of quantitation (LLOQ) of 1 ng/mL. Intra-day precision was less than 11%, and inter-day precision was less than 12%. The accuracy was between 92.0% and 108.7%, the recovery was better than 89.6%, and the matrix effect was between 85.9% and 98.6%. The method was successfully applied to a pharmacokinetic study of byakangelicol after intravenous and oral administration, and the absolute bioavailability was 3.6%.

scholarly journals High Performance Liquid Chromatographic Assay for the Simultaneous Determination of Posaconazole and Vincristine in Rat Plasma

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Hadeel A. Khalil ◽  
Ahmed F. El-Yazbi ◽  
Tarek S. Belal ◽  
Dalia A. Hamdy
Keyword(s):  
Simultaneous Determination ◽  
High Performance ◽  
Sodium Hydroxide Solution ◽  
Plasma Concentrations ◽  
High Performance Liquid Chromatographic ◽  
Rat Plasma ◽  
Organic Layer ◽  
Sprague Dawley ◽  
Limit Of Quantitation

Purpose. Developing a validated HPLC-DAD method for simultaneous determination of posaconazole (PSZ) and vincristine (VCR) in rat plasma.Methods. PSZ, VCR, and itraconazole (ITZ) were extracted from 200 μL plasma using diethyl ether in the presence of 0.1 M sodium hydroxide solution. The organic layer was evaporated in vacuo and dried residue was reconstituted and injected through HC-C18 (4.6 × 250 mm, 5 μm) column. In the mobile phase, acetonitrile and 0.015 M potassium dihydrogen orthophosphate (30 : 70 to 80 : 20, linear gradient over 7 minutes) pumped at 1.5 mL/min. VCR and PSZ were measured at 220 and 262 nm, respectively. Two Sprague Dawley rats were orally dosed PSZ followed by iv dosing of VCR and serial blood sampling was performed.Results. VCR, PSZ, and ITZ were successfully separated within 11 min. Calibration curves were linear over the range of 50–5000 ng/mL for both drugs. The CV% and % error of the mean were ≤18% and limit of quantitation was 50 ng/mL for both drugs. Rat plasma concentrations of PSZ and VCR were simultaneously measured up to 72 h and their calculated pharmacokinetics parameters were comparable to the literature.Conclusion.The assay was validated as per ICH guidelines and is appropriate for pharmacokinetics drug-drug interaction studies.

scholarly journals Separacja prawna małżeństwa w kontekście nietrwałości małżeństwa ponowoczesnego

2016 ◽  
pp. 249-261
Author(s):  
Urszula Miernik
Keyword(s):  
The State ◽  
Marriage And Family ◽  
Social State ◽  
The Stability ◽  
The Individual

The changes in the postmod­ern world significantly influenced on the marriage and family. Impermanence of the marital bond is the characteristic for contemporary relations in marriage. „Society of risk” puts on the individual the duty of creating his/her own bibliog­raphy and marriage becomes not a con­struct but a process. The object of in­terest of the paper is separation of mar­riage. The name of the phenomena de­scribes the factual and the legal state of the spouses which appeared after the breakdown of the life together. Legal in­stitution of separation is a specific legal figure which, in the perspective of a so­ciety, places the individuals in the state of suspension. Uniqueness of the state reminds the liminal phase distinguished in the process of ceremonies of passage (Arnold van Gennep). Every significant event in the life of a man, it is a passage from one social state to another (which is strictly defined). Liminal stage is a pe­riod of exclusion – to be in the between. Legal separation can be depicted as a pe­riod of some kind of marginalization of an individual. It uniqueness is built on this that an individual can ultimately define himself/herself by restoration of marital life. In this case it will be recon­stitution function of separation. The per­son can take decision about termination of his/her marriage by divorce. There is also possibility of remaining in separa­tion without any determination of the period of its ending. The aim of the pa­per is the try to get the answer on following question: does the institution of sep­aration favour the stability of marriage?

scholarly journals UPLC-MS/MS Method for the Simultaneous Quantification of Eight Compounds in Rat Plasma and Its Application to a Pharmacokinetic Study after Oral Administration of Veratrum (Veratrum nigrum L.) Extract

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yuqi Fan ◽  
Lulu Zhao ◽  
Xuhua Huang ◽  
Jiayuan Shen ◽  
Wei Wang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Internal Standard ◽  
Rat Plasma ◽  
Negative Ion ◽  
Pharmacokinetic Parameters ◽  
Relative Standard ◽  
Antifungal Effects ◽  
The Matrix ◽  
The Stability

Veratrum nigrum L. is a well-known traditional Chinese medicine with a lot of pharmacological activities including antihypertensive, anticancer, and antifungal effects. In the current experiment, a rapid and sensitive UPLC-MS/MS method that takes only 7 min run time has been established and validated for simultaneous determination of eight bioactive compounds including cyclopamine, jervine, veratramine, polydatin, quercetin, apigenin, resveratrol, and veratrosine in rat plasma. The chromatographic separation of analytes and internal standard was performed on a Phenyl-Hexyl column ( 2.1 × 100   mm , 1.7 μm) with the mobile phase consisting of water (0.1% formic acid) and acetonitrile at a flow rate of 0.3 mL/min. An electrospray ionization (ESI) source was used to detect the samples in both positive and negative ion modes. The intra- and interday precisions of the compounds were less than 9.5% and the accuracy ranged from -10.8% to 10.4%. The extraction recoveries of the compounds were in the range of 85.1 ± 1.5 % to 102.6 ± 8.0 % , and the matrix effect ranged from 91.2 ± 4.5 % to 113.8 ± 1.5 % . According to the results of the stability test, the eight compounds have good stability under various conditions and the relative standard deviation (RSD) less than 13.2%. The pharmacokinetic parameters of the eight compounds in rat plasma after oral administration of Veratrum nigrum L. extract were successfully determined by the established UPLC-MS/MS method.

scholarly journals Determination and pharmacokinetics of calycanthine in rat plasma by UPLC-MS/MS

2020 ◽  
Author(s):  
Meifei Lu ◽  
Xiaojie Lu ◽  
Zheng Yu ◽  
Congcong Wen
Keyword(s):  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Precipitation Method ◽  
Absolute Bioavailability ◽  
Limit Of Quantification ◽  
The Matrix ◽  
Acid Aqueous Solution

AbstractCalycanthine is an important class of alkaloids extracted and isolated from the roots, leaves, flowers and fruits of Chimonanthus praecox. In this work, the UPLC-MS/MS method was used for determination of calycanthine in rat plasma, and the pharmacokinetics in rats were investigated. Midazolam was used as an internal standard (IS), and methanol precipitation method was used to pretreatment the rat plasma samples. Chromatographic separation was achieved on a UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column with the mobile phase of methanol- 0.1% formic acid aqueous solution with gradient elution. Multiple reaction monitoring (MRM) mode with positive ionization was applied for quantitative analysis, m/z 347.3 → 246.7 and 326.2 → 291.4 for calycanthine and IS, respectively. The results indicated that within the range of 1–200 ng/mL, linearity of calycanthine in rat plasma was good (r > 0.995), and the lower limit of quantification (LLOQ) was 1 ng/mL. Accuracy range was between 90.6 and 109.4%, precision (RSD) of calycanthine was less than 14%. The matrix effect was between 97.9% and 105.4%, the recovery was better than 85.6%. The developed UPLC-MS/MS method was successfully applied in the pharmacokinetics of calycanthine in rats after oral and intravenous administration. The absolute bioavailability of the calycanthine was 37.5% in rats.

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