scholarly journals Pharmacokinetics and Tissue Distribution of a Novel Bis-Chelated Gold(I) Diphosphine Compound, Bis(2,3-bis(tert-butylmethylphosphino)Quinoxaline)Aurate(I), in Rats

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2082
Author(s):  
Ying Peng ◽  
Huanhuan Qi ◽  
Qingqing Chang ◽  
Yu Zhang ◽  
Weiyi Liu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tissue Distribution ◽  
Intravenous Administration ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Tissue Homogenate ◽  
Ionization Source ◽  
Pharmacokinetic Properties ◽  
Rat Tissue

GC20, a novel soluble bis-chelated gold(I)−diphosphine compound, has been reported as a promising anticancer candidate. Assessing the pharmacokinetic properties of GC20 is critical for its medicinal evaluation. First, a sensitive and specific liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed and well validated to determine GC20 in rat plasma and rat tissue homogenate after one step protein precipitation. Chromatographic separation was achieved on an Angilent ZORBAX-C18 column (3.5 μm, 2.1 × 50 mm) with gradient elution and mass spectrometry was performed on a triple quadrupole in positive ion mode using an electrospray ionization source. This method was then applied to investigate the pharmacokinetics and tissue distribution of GC20 in rats after intravenous administration. The results showed that the plasma exposure of GC20 in vivo increased with increasing doses after a single dose. However, after multiple doses, a significant accumulation and a saturation at elimination were observed for GC20 in rats. Moreover, after intravenous administration, GC20 was widely distributed in various tissues, with the highest levels in the lung, spleen, liver, and pancreas, followed by the kidney and heart, while the lowest level was found in the brain. This is the first report on the pharmacokinetic properties of GC20.

scholarly journals Pharmacokinetics and Tissue Distribution of Alnustone in Rats after Intravenous Administration by Liquid Chromatography-Mass Spectrometry

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3183 ◽  
Author(s):  
Yang Song ◽  
Yu Zhou ◽  
Xiao-Ting Yan ◽  
Jing-Bo Bi ◽  
Xin Qiu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Formic Acid ◽  
Tissue Distribution ◽  
Intravenous Administration ◽  
Peak Plasma ◽  
Internal Standard ◽  
Pharmacokinetic Studies ◽  
The Mean

Alnustone, a nonphenolic diarylheptanoid, first isolated from Alnus pendula (Betulaceae), has recently received a great deal of attention due to its various beneficial pharmacological effects. However, its pharmacokinetic profile in vivo remains unclear. The purpose of this study is to establish a fast and sensitive quantification method of alnustone using liquid chromatography tandem mass spectrometry (LC-MS/MS) and evaluate the pharmacokinetic and tissue distribution profiles of alnustone in rats. The sample was precipitated with acetonitrile with 0.5% formic acid and separated on BEH C18 Column. The mobile phase was composed of 0.1% formic acid in water and methanol at a flow rate of 0.3 mL/min. Alnustone and the internal standard (caffeine) were quantitatively monitored with precursor-to-product ion transitions of m/z 262.9→105.2 and m/z 195.2→138.0, respectively. The calibration curve for alnustone was linear from 1 to 2000 ng/mL. The intra- and inter-day assay precision (RSD) ranged from 1.1–9.0 % to 3.3–8.6%, respectively and the intra- and inter-day assay accuracy (RE) was between −8.2–9.7% and −10.3–9.9%, respectively. The validated method was successfully applied to the pharmacokinetic studies of alnustone in rats. After single-dose intravenous administration of alnustone (5 mg/kg), the mean peak plasma concentration (Cmax) value was 7066.36 ± 820.62 ng/mL, and the mean area under the concentration-time curve (AUC0–t) value was 6009.79 ± 567.30 ng/mL∙h. Our results demonstrated that the residence time of alnustone in vivo was not long and it eliminated quickly from the rat plasma. Meanwhile, the drug is mainly distributed in tissues with large blood flow, and the lung and liver might be the target organs for alnustone efficacy. The study will provide information for further application of alnustone.

scholarly journals Pharmacokinetics and Tissue Distribution Study of Chlorogenic Acid from Lonicerae Japonicae Flos Following Oral Administrations in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Yulu Zhou ◽  
Ting Zhou ◽  
Qi Pei ◽  
Shikun Liu ◽  
Hong Yuan
Keyword(s):  
Mass Spectrometry ◽  
Oral Administration ◽  
Chlorogenic Acid ◽  
Tissue Distribution ◽  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Tissue Homogenate ◽  
Ionization Mass

Chlorogenic acid (ChA) is proposed as the major bioactive compounds of Lonicerae Japonicae Flos (LJF). Forty-two Wistar rats were randomly divided into seven groups to investigate the pharmacokinetics and tissue distribution of ChA, via oral administration of LJF extract, using ibuprofen as internal standard, employing a high performance liquid chromatography in conjunction with tandem mass spectrometry. Analytes were extracted from plasma samples and tissue homogenate by liquid–liquid extraction with acetonitrile, separated on a C18 column by linear gradient elution, and detected by electrospray ionization mass spectrometry in negative selected multiple reaction monitoring mode. Our results successfully demonstrate that the method has satisfactory selectivity, linearity, extraction recovery, matrix effect, precision, accuracy, and stability. Using noncompartment model to study pharmacokinetics, profile revealed that ChA was rapidly absorbed and eliminated. Tissue study indicated that the highest level was observed in liver, followed by kidney, lung, heart, and spleen. In conclusion, this method was suitable for the study on pharmacokinetics and tissue distribution of ChA after oral administration.

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.

scholarly journals Pharmacokinetics of isocorynoxeine in rat plasma after intraperitoneal administration by UPLC–MS/MS

2020 ◽  
Vol 32 (4) ◽  
pp. 260-263
Author(s):  
Haichao Zhan ◽  
Zhen Wei ◽  
Ke Ren ◽  
Shuhua Tong ◽  
Xianqin Wang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Multiple Reaction Monitoring ◽  
Intraperitoneal Administration ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Tandem Mass ◽  
Relative Standard ◽  
Liquid Chromatography Tandem Mass

Isocorynoxeine is one of the main alkaloids in Chinese medicinal herbs, and has pharmacological activities such as antihypertensive, sedative, anticonvulsant, and neuronal protection. It is an effective component of Uncaria for the treatment of hypertension. In this study, we used a fast and sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) to detect isocorynoxeine in rat plasma and investigated its pharmacokinetics in rats. Six rats were given isocorynoxeine (15 mg/kg) by intraperitoneal (i.p.) administration. Blood (100 μL) was withdrawn from the caudal vein at 5 and 30 min and 1, 2, 4, 6, 8, 12, and 24 h after administration. Chromatographic separation was achieved using a UPLC BEH C18 column using a mobile phase of acetonitrile–0.1% formic acid with gradient elution. Electrospray ionization (ESI) tandem mass spectrometry in the multiple reaction monitoring (MRM) mode with positive ionization was applied. Intra-day and inter-day precisions (relative standard deviation, %RSD) of isocorynoxeine in rat plasma were lower than 12%. The method was successfully applied in the pharmacokinetics of isocorynoxeine in rats after intraperitoneal administration. The t1/2 of isocorynoxeine is 4.9 ± 2.1 h, which indicates quick elimination.

scholarly journals Simultaneous Quantification of Four Phenylethanoid Glycosides in Rat Plasma by UPLC-MS/MS and Its Application to a Pharmacokinetic Study of Acanthus Ilicifolius Herb

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3117 ◽  
Author(s):  
Mengqi Zhang ◽  
Xia Ren ◽  
Shijun Yue ◽  
Qing Zhao ◽  
Changlun Shao ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Multiple Reaction Monitoring ◽  
Folk Medicine ◽  
Ethanol Extract ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Molecular Structures ◽  
Intragastric Administration ◽  
Phenylethanoid Glycosides ◽  
Acanthus Ilicifolius

Acanthus ilicifolius herb (AIH), the dry plant of Acanthus ilicifolius L., has long been used as a folk medicine for treating acute and chronic hepatitis. Phenylethanoid glycosides (PhGs) are one family of the main components in AIH with hepatoprotective, antioxidant, and anti-inflammatory activities. In this study, the pharmacokinetics of AIH was investigated preliminarily by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS). A simultaneously quantitative determination method for four PhGs (acteoside, isoacteoside, martynoside, and crenatoside) in rat plasma was first established by UPLC-MS/MS. These four PhGs were separated with an ACQUITY UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm) by gradient elution (mobile phase: MeCN and 0.1% formic acid in water, 0.4 mL/min). The mass spectrometry detection was performed using negative electrospray ionization (ESI−) in multiple reaction monitoring (MRM) mode. By the established method, the preliminary pharmacokinetics of AIH was elucidated using the kinetic parameters of the four PhGs in rat plasma after intragastric administration of AIH ethanol extract. All four PhGs showed double peaks on concentration-time curves, approximately at 0.5 h and 6 h, respectively. Their elimination half-lives (t1/2) were different, ranging from 3.42 h to 8.99 h, although they shared similar molecular structures. This work may provide a basis for the elucidation of the pharmacokinetic characteristics of bioactive components from AIH.

scholarly journals Development and Validation of a Sensitive UHPLC-MS/MS Method for the Measurement of Gardneramine in Rat Plasma and Tissues and its Application to Pharmacokinetics and Tissue Distribution Study

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3953 ◽  
Author(s):  
Zhao ◽  
Tan ◽  
Chen ◽  
Sun ◽  
Wang ◽  
...  
Keyword(s):  
Multiple Reaction Monitoring ◽  
Indole Alkaloid ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Limit Of Quantification ◽  
Tissue Samples ◽  
Distribution Study

As a novel monoterpenoid indole alkaloid, gardneramine has been confirmed to possess excellent nervous depressive effects. However, there have been no reports about the measurement of gardneramine in vitro and in vivo. The motivation of this study was to establish and validate a specific, sensitive, and robust analytical method based on UHPLC-MS/MS for quantification of gardneramine in rat plasma and various tissues after intravenous administration. The analyte was extracted from plasma and tissue samples by protein precipitation with methanol using theophylline as an internal standard (I.S.). The analytes were separated on an Agilent ZORBAX Eclipse Plus C18 column using a gradient elution of acetonitrile and 0.1% formic acid in water at a flow rate of 0.3 mL/min. Gardneramine and I.S. were detected and quantified using positive electrospray ionization in multiple reaction monitoring (MRM) mode with transitions of m/z 413.1→217.9 for gardneramine and m/z 181.2→124.1 for I.S.. Perfect linearity range was 1–2000 ng/mL with a correlation coefficient (r2) of ≥0.990. The lower limit of quantification (LLOQ) of 1.0 ng/mL was adequate for application to different preclinical studies. The method was successfully applied for determination of gardneramine in bio-samples.

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 Development and Validation of a Bioanalytical Method for 3′- and 6′-Sialyllactose in Minipig Liver and Kidney Using Liquid Chromatography-Tandem Mass Spectrometry and Its Application to Analysis of Tissue Distribution

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5721
Author(s):  
Han Young Eom ◽  
Seok-In Jang ◽  
Jong-Hwa Lee
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Tissue Distribution ◽  
Gradient Elution ◽  
Tandem Mass ◽  
Bioanalytical Method ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Liver And Kidney

Breast milk contains human milk oligosaccharides (HMOs), including sialyllactose (SL). SL is composed of sialic acid and lactose, and is divided into 3′-SL and 6′-SL according to the binding position. SL has immunoprotective effects against bacteria and viruses, and acts as a probiotic in the gastrointestinal tract. In this study, we developed a bioanalytical method for simultaneous analysis of 3′-SL and 6′-SL in liver and kidney tissues of Yucatan minipigs using liquid chromatography–tandem mass spectrometry (LC-MS/MS) under conditions optimized in our previous study. LC-MS/MS was performed using a hydrophilic interaction liquid chromatography (HILIC) column (50 mm × 2.1 mm, 3 μm) with a mobile phase consisting of 10 mM ammonium acetate in water (pH 4.5) and acetonitrile with gradient elution at a flow rate of 0.3 mL/min. A surrogate matrix method using water was applied for analysis of endogenous SL. The developed method was validated with regard to selectivity, linearity, precision, accuracy, the matrix effect, recovery, parallelism, dilution integrity, carryover, and stability according to the US Food and Drug Administration guidelines. We performed a tissue distribution study of minipigs, and analyzed liver and kidney tissues using the developed method to determine the tissue distribution of 3′-SL and 6′-SL. The tissue concentrations of 3′-SL and 6′-SL were readily measurable, suggesting that the method would be useful for evaluating the tissue distributions of these compounds in minipigs.

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