An Application of Microdialysis to Drug Tissue Distribution Study: In Vivo Evidence for Free-Ligand Hypothesis and Tissue Binding of .BETA.-Lactam Antibiotics in Interstitial Fluids.

Abstract Background Tadehaginoside, an active ingredient isolated from Tadehagi triquetrum L., exhibited various biological activities. However, the pharmacokinetics and tissue-distribution which affects tadehaginoside’s therapeutic actions and application remain elusive.MethodsTo clarify the metabolism of tadehaginoside in vivo, a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established to detect the level of tadehaginoside in plasma and eleven tat tissues (brain, heart, liver, spleen, lungs, kidneys, stomach, small intestine, skeletal muscle, body fat, and testes). Besides, this validated method was also successfully applied to the quantitative determination of its metabolite, p-hydroxycinnamic acid (HYD) in plasma. The pharmacokinetic and tissue-distribution of tadehaginoside were investigated by this developed method. ResultsThe pharmacokinetic study indicated that tadehaginoside in plasma of rats with intragastric administration showed relatively low concentration may be due to the formation of its metabolite, and the quick absorption of tadehaginoside was detected following intravenous administration. Tissue-distribution study indicated that kidney and spleen were the major distribution organs for tadehaginoside in rats. ConclusionsThese results could provide clues for exploring the bioactivity of tadehaginoside based on its pharmacokinetic characteristics.

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Tissue Distribution Study of Poloxamer188 in Rats by Ultra-High-Performance Liquid Chromatography Quadrupole Time of Flight/Mass Spectrometry with MSALL-Based Approach

Molecules ◽

10.3390/molecules26185644 ◽

2021 ◽

Vol 26 (18) ◽

pp. 5644

Author(s):

Yixuan Feng ◽

Lele Li ◽

Yuxuan Li ◽

Xinxin Zhou ◽

Xiaoying Lin ◽

...

Keyword(s):

Mass Spectrometry ◽

Quantitative Analysis ◽

Tissue Distribution ◽

High Performance ◽

Time Of Flight ◽

Stomach Muscle ◽

Distribution Study ◽

Flight Mass Spectrometry ◽

Tissue Distribution Study

Poloxamer188 (PL188), as one of the most commonly used pharmaceutical excipients, has unique physicochemical properties and good biocompatibility, and so is playing an increasingly extensive role in the field of medicine. Currently, there are few studies on the tissue distribution of PL188 in vivo. In this study, the LC-MS method based on MSALL technique of quadrupole time of flight mass spectrometry for absolute quantitative analysis of poloxamer 188 in biological substrates was established for the first time. The tissue distribution of poloxamer188 in SD rats were studied using the established quantitative analysis method. To explore the distribution of PL188 in organs and tissues, PL188 was administered via rat tail vein at a dose of 5 mg/kg. Eight kinds of tissues including heart, liver, spleen, lung, kidney, stomach, muscle and brain of rats were collected at 0.25 h, 1 h and 4 h after administration. Tissue distributions showed the highest level was observed in kidney, then in stomach, which indicated PL188 mainly bioaccumulated in the kidney. This study can provide references for the further study of PL188.

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Pharmacokinetics and Tissue Distribution Study of Pinosylvin in Rats by Ultra-High-Performance Liquid Chromatography Coupled with Linear Trap Quadrupole Orbitrap Mass Spectrometry

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/4181084 ◽

2018 ◽

Vol 2018 ◽

pp. 1-14 ◽

Cited By ~ 4

Author(s):

Yuhang Fu ◽

Xiaoya Sun ◽

Lili Wang ◽

Suiqing Chen

Keyword(s):

Mass Spectrometry ◽

High Performance Liquid Chromatography ◽

Liquid Chromatography ◽

Tissue Distribution ◽

High Performance ◽

Gastric Ulcers ◽

Pharmacokinetic Parameters ◽

Distribution Study ◽

Tissue Distribution Study

Pinosylvin is a potential anti-inflammatory and antioxidant compound and the major effective medicinal ingredient in the root of Lindera reflexa Hemsl. However, few investigations have been conducted regarding the pharmacokinetics, excretion, characteristics of tissue distribution, and major metabolites of pinosylvin in rats after oral administration. To better understand the behavior and mechanisms of action underlying the activity of pinosylvin in vivo, we established a simple, sensitive, and reliable ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for quantifying pinosylvin in rat plasma, urine, feces, and various tissues (including heart, liver, spleen, lung, kidneys, large intestine, small intestine, and stomach). Noncompartmental pharmacokinetic parameters indicated that pinosylvin is rapidly distributed and taken up by tissues. The time to peak (maximum) concentration (Tmax) was 0.137 h, and the apparent elimination half-life (t1/2) was 1.347±0.01 h. The results of the tissue distribution study suggest that pinosylvin is widely distributed to various tissues; the highest concentration was observed after 10 min in the stomach, followed by the heart, lung, spleen, and kidneys. Results of the excretion study suggest that a small amount of pinosylvin is excreted from the urine and feces in the parent form; the 73 h accumulative excretion ratios of urine and feces were 0.82% and 0.11%, respectively. It is likely that pinosylvin is mostly metabolized in vivo. Nine metabolites were found, and the main metabolic pathways of pinosylvin in rats included glucuronidation, hydroxylation, and methylation. Four metabolites had higher concentrations in the stomach, suggesting that the stomach is a potential target organ of pinosylvin. In conclusion, the present study may provide a material basis for studying the pharmacological action of pinosylvin and provides meaningful information for the clinical treatment of chronic gastritis and gastric ulcers using Radix Linderae Reflexae.

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Pharmacokinetics and Tissue Distribution Study of Ferruginol in Wistar Rat by High-performance Liquid Chromatography

Current Pharmaceutical Analysis ◽

10.2174/1573412914666180508154147 ◽

2018 ◽

Vol 15 (1) ◽

pp. 67-73 ◽

Cited By ~ 1

Author(s):

Guiyun Cao ◽

Suqiao Han ◽

Keke Li ◽

Li Shen ◽

Xiaohong Wang ◽

...

Keyword(s):

Tissue Distribution ◽

Mobile Phase ◽

High Performance ◽

Wistar Rat ◽

Freezing And Thawing ◽

Promising Candidate ◽

Distribution Study ◽

Substance Loss ◽

Tissue Distribution Study ◽

The Brain

Background: Ferruginol (FRGN) exhibits a broad range of pharmacological properties which make it a promising candidate for chemoprevention. However, little is known about its absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Methods: A rapid, sensitive and specific HPLC-DAD method was established to quantify FRGN in the plasma and tissues of Wistar rats. After extraction of FRGN with ethyl acetate (EtOAc), chromatographic separation was performed on a YMC ODS C18 column (250 × 4.6 mm I.D., 5 µm) with a mobile phase consisting of methanol-water (92:8, v/v) at a flow rate of 0.9 mL/min. Detection was conducted with a wavelength of 273 nm at 25 °C. Results: The calibration curves for FRGN were linear in the concentration range of 0.5-20 µg/mL for plasma, 0.5-10 µg/mL for heart, liver, spleen, lung, kidney, stomach, intestine, brain and muscle. After three cycles of freezing and thawing, the concentration variations were within ± 7% of nominal concentrations, indicating no significant substance loss during repeated thawing and freezing. The assay was applied to pharmacokinetic and tissue distribution study in rats. Results suggested that lung, heart, liver, spleen and kidney were the major distribution tissues of FRGN in rats, and FRGN could permeate the blood-brain barrier to distribute in the brain of rats. Conclusion: The information provided by this research is very useful for gaining knowledge of the pharmacokinetic process and tissue distribution of FRGN.

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