scholarly journals Comparative Pharmacokinetic Study of Taxifolin after Oral Administration of Fructus Polygoni Orientalis Extract in Normal and Fibrotic Rats by UPLC-MS/MS

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Feili Wei ◽  
Li Guo ◽  
Yongsong Xu ◽  
Dexi Chen ◽  
Muxin Gong
Keyword(s):  
Liver Fibrosis ◽  
Oral Administration ◽  
Residence Time ◽  
Mean Residence Time ◽  
Internal Standard ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Porcine Serum ◽  
Validation Parameters ◽  
The Mean

Fructus polygoni orientalis (FPO) is widely used in clinical practice in China, especially in treatment of liver diseases including viral hepatitis, liver fibrosis, and liver cirrhosis. However, its pharmacokinetic (PK) alterations in liver fibrotic rats have rarely been reported. To study whether taxifolin, one of the main flavonoids in FPO can be absorbed into blood after oral administration of FPO extract and to compare the differences in pharmacokinetic parameters of taxifolin to normal and liver fibrotic rats induced by porcine serum (PS), a UPLC-MS/MS method was developed and validated for determination of taxifolin in rat plasma using puerarin as the internal standard (IS). All validation parameters met the acceptance criteria according to regulatory guidelines. The results indicated that after treatment of rats with PS alone for 12 weeks, the liver fibrotic model group was built successfully. The taxifolin can be absorbed into the blood after oral administration of the FPO extract. The Cmax of taxifolin was 1940 ± 502.2 ng/mL and 2648 ± 208.5 ng/mL (p<0.05), the AUC0∼t of taxifolin was 4949.7 ± 764.89 h·ng/mL and 6679.9 ± 734.26 h·ng/mL (p<0.05), the AUC0∼∞ of taxifolin was 5049.4 ± 760.7 and 7095.2 ± 962.3 h·ng/mL (p<0.05), and the mean residence time (MRT) of taxifolin was 2.46 ± 0.412 h and 3.17 ± 0.039 h (p<0.05) in the normal and fibrotic model groups, respectively. These results confirmed that the pharmacokinetic parameters of taxifolin are altered in liver fibrosis, manifested as Cmax, AUC0∼t, AUC0∼∞, and the mean residence time (MRT). It suggested that it is essential to consider the characteristics of pharmacokinetics after oral administration of FPO in liver disease patients.

scholarly journals Studies of the pharmacokinetics of morroniside and loganin in rat after oral administration of raw and wine-processed Corni fructus by UPLC-QqQ-MS/MS

2022 ◽  
Vol 20 (2) ◽  
pp. 411-418
Author(s):  
Wei Wang ◽  
Xuechun Wang ◽  
Qiang Zhang ◽  
Ru Jia ◽  
Chunjie Du ◽  
...  
Keyword(s):  
Oral Administration ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Negative Ion ◽  
Pharmacokinetic Parameters ◽  
Tissue Samples ◽  
Multiple Reaction Monitoring Mode ◽  
The Mean ◽  
Corni Fructus ◽  
Negative Ion Mode

Purpose: To study the pharmacokinetics of morroniside (MR) and loganin (LG) in rats after oral administration of raw and wine-processed Corni fructus by UPLC-QqQ-MS/MS. Methods: Arctiin (AT) was used as internal standard, and the plasma or tissue samples were extracted twice using ethyl acetate. Electrospray ionization (ESI) negative ion mode was used, and the multiple reaction monitoring mode (MRM) was set in acquisition mode. The extraction and detection method is supported by selectivity, sensitivity, precision, accuracy, stability, extraction, recovery and matrix effect. The non-atrioventricular model of das2.0 software was used to calculate the pharmacokinetic parameters. Results: The absorption rate of MR (PTmax=0.092) and LG (PTmax=0.092) in Corni Fructus after wine-processing was faster in rats. The mean residence time was longer, and distribution of MR (PMRT0~t = 0.294) and LG (PMRT0~t = 0.000) in wine-processed Corni Fructus group increased in liver and kidneys. Conclusion: The proposed method has been successfully validated and is suitable for studying the pharmacokinetics of the two analytes in rats.

scholarly journals Comparative pharmacokinetic study of five flavonoids in normal rats and rats with gastric ulcer following oral administration of Mongolian medicine, Shudage - 4 by UPLC – ESI – MS/MS

2020 ◽  
Vol 19 (3) ◽  
pp. 651-659
Author(s):  
Xin Jia ◽  
Yinfei Du ◽  
Jia Xu ◽  
Yu Dong
Keyword(s):  
Gastric Ulcer ◽  
Oral Administration ◽  
Internal Standard ◽  
Rat Plasma ◽  
Negative Ion ◽  
Selected Reaction Monitoring ◽  
Pharmacokinetic Parameters ◽  
Ionization Mass ◽  
Plasma Samples ◽  
Esi Ms

Purpose: To develop a simple, rapid and sensitive ultra-performance liquid chromatography - electrospray ionization-mass spectrometry (UPLC–ESI–MS/MS) method was developed and fully validated for the simultaneous determination of galangin, kaempferide, galangin-3-methylether, kaempferol and quercetin in rat plasma after oral administration of Mongolian Medicine, Shudage-4 extracts. Methods: The galangin, kaempferide, galangin-3-methylether, kaempferol and quercetin were separated on a C18 column using 0.1 % formic acid at a flow rate of 0.4 mL / min and detected by a mass spectrometer in negative-ion mode with selected reaction monitoring (SRM) mode. Plasma samples were processed with a simple deproteinization technique using ethyl acetate and acetonitrile. Following the protein precipitation, the plasma samples were evaporated under gentle stream of nitrogen and analyzed by above method. Naringin was used as an internal standard (IS). Method validation was performed according to the Chinese Food and Drug Administration guidelines. Results: A good linearity (r2 ≥ 0.9990) was showed by the UPLC – ESI – MS / MS method, the low limits of quantification for galangin, kaempferide, galangin-3-methylether, kaempferol and quercetin were 229.8, 78.8, 32.0, 123.7 and 137.8 ng / mL, respectively. The results of inter-day and intra-day precisions met the experimental requirement (< 7.8 %). The matrix effect and recovery efficiency of the five analytes were more than 72.9 and 88.7 % respectively. The stability of the analytes were satisfactory. The UPLC – ESI – MS / MS method has been used for the five analytes’ pharmacokinetics study successfully after gastrointestinal route of the Mongolian Medicine Shudage-4. The pharmacokinetic parameters showed significant differences (P < 0.05) between the normal and gastric ulcer groups. The metabolism and transport of the five analytes in gastric ulcer rates were faster than in normal rats after administration of Shudage - 4 extract. Double-peak phenomenon appeared in galangin, galangin – 3 - methylether and quercetin. Conclusion: The results suggest that the metabolism and transport of Mongolian Medicine Shudage-4 in gastric ulcer rats is faster than in normal rats and may be enriched and acted on at the lesion site. Keywords: UPLC – ESI – MS / MS; Mongolian medicine; Shudage - 4; pharmacokinetics; gastric ulcer

Simultaneous Determination of Four Bioactive Flavonoids in Rat Plasma by UPLC–MS/MS and Comparative Pharmacokinetic Study after Oral Administration of Danyikangtai Powder and Three Compatibilities

2020 ◽  
Vol 16 ◽  
Author(s):  
Yihe Huang ◽  
Yanhui Zhao ◽  
Yumeng Zhang ◽  
Lin Sun ◽  
Chunjie Zhao ◽  
...  
Keyword(s):  
Oral Administration ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Drug Candidate ◽  
Pharmacokinetic Parameters ◽  
Simultaneous Treatment ◽  
Scutellariae Radix

Background: Danyikangtai powder, a traditional Chinese medicine (TCM) formula, shows promise to become a novel drug candidate for the simultaneous treatment of chronic cholecystitis and chronic pancreatitis. However, the pharmacokinetic behavior of Danyikangtai powder remains unclear. Objective: We investigated the comparative pharmacokinetics of four flavonoids in rats after oral administration of Danyikangtai powder and three compatibilites. Materials and methods: The comparative pharmacokinetics was studied by ultra performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS). Chromatographic separation was performed on an Universil XB-C18 column with a gradient mobile phase containing 0.1% (v/v) aqueous formic acid and acetonitrile. All analytes and internal standard were quantitated in the multiple reaction monitoring mode with a positive electrospray ionization interface. Results and discussion: Danyikangtai powder and Scutellariae radix have similar pharmacokinetic behaviors in rats after oral administration. However, the elimination of four flavonoids in rats after oral administration of Danyikangtai powder was accelerated, which was possibly related to the reduction of the potential hepatotoxicity of Scutellariae radix. The varying degrees of change in pharmacokinetic parameters after oral administration of different herb combinations suggested that herb–herb interactions occurred in vivo. Conclusions: This study will be helpful to reveal the safety, rational and mechanism of Danyikangtai powder formula compatibility, thereby providing pre-clinical research data for its new drug development and guidance for its rational clinical application.

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 Simultaneous quantification of five bioactive 16-deoxybarringtogenol C triterpenoid saponins in rat plasma by HPLC-MS: Application to a pharmacokinetic study after oral administration of Xanthoceras sorbifolia Bunge husks extract

2020 ◽  
Author(s):  
Weiwei Rong ◽  
Zheng Sun ◽  
Yina Guan ◽  
Ran Liu ◽  
Qing Li ◽  
...  
Keyword(s):  
Oral Administration ◽  
Pharmacokinetic Study ◽  
Internal Standard ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Liquid Chromatography Mass Spectrometry ◽  
Established Method ◽  
Triterpenoid Saponins ◽  
Terminal Half Life ◽  
Insight Into

AbstractIn this study, a simple and rapid liquid chromatography-mass spectrometry method was developed to simultaneously determinate five 16-deoxybarringtogenol C triterpenoid saponins with the potential of neuroprotection in rat plasma following the oral administration of the Xanthoceras sorbifolia Bunge husks extract. With digoxin as the internal standard, the plasma samples were pre-treated by ethyl acetate-isopropanol (1:1, v/v). The chromatographic separation of the five analytes was performed using a Phenomenex C18 column (250 mm × 4.6 mm, 5.0 mm) with a mobile phase of 0.05% formic acid (A)-acetonitrile (B). The mass spectrometric detection was carried out in the selected ion mode in positive ionization. The extraction recoveries of the five analytes were all over 71.28%. The established method was fully validated in line with the ICH and Food and Drug Administration (FDA) guidelines and successfully applied to the pharmacokinetic study on the five analytes in rat plasma. The terminal half-life (t1/2) of the five analytes was 2.92 ± 0.57, 5.52 ± 1.75, 2.48 ± 0.62, 2.95 ± 0.94, and 2.34 ± 0.81, respectively. This study was purposed to investigate the oral pharmacokinetic parameters and gain an in-depth insight into the reasonable preclinical use of the husks extract derived from X. sorbifolia Bunge.

scholarly journals UPLC-MS/MS of Atractylenolide I, Atractylenolide II, Atractylenolide III, and Atractyloside A in Rat Plasma after Oral Administration of Raw and Wheat Bran-Processed Atractylodis Rhizoma

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3234 ◽  
Author(s):  
Shizhao Xu ◽  
Xiaojie Qi ◽  
Yuqiang Liu ◽  
Yuhan Liu ◽  
Xin Lv ◽  
...  
Keyword(s):  
Oral Administration ◽  
Wheat Bran ◽  
Multiple Reaction Monitoring ◽  
Area Under The Curve ◽  
Internal Standard ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Weighting Method ◽  
Relative Standard

Atractylodis Rhizoma is the dried rhizome of Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz and is often processed by stir-frying with wheat bran to reduce its dryness and increase its spleen tonifying activity. However, the mechanism by which the processing has this effect remains unknown. To explain the mechanism based on the pharmacokinetics of the active compounds, a rapid, sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was developed to analyze atractylenolides I, II, and III, and atractyloside A simultaneously in rat plasma after oral administration of raw and processed Atractylodis Rhizoma. Acetaminophen was used as the internal standard and the plasma samples were pretreated with methanol. Positive ionization mode coupled with multiple reaction monitoring mode was used to analyze the four compounds. The method validation revealed that all the calibration curves displayed good linear regression over the concentration ranges of 3.2–350, 4–500, 4–500, and 3.44–430 ng/mL for atractylenolides I, II, and III, and atractyloside A, respectively. The relative standard deviations of the intra- and inter-day precisions of the four compounds were less than 6% with accuracies (relative error) below 2.38%, and the extraction recoveries were more than 71.90 ± 4.97%. The main pharmacokinetic parameters of the four compounds were estimated with Drug and Statistics 3.0 and the integral pharmacokinetics were determined based on an area under the curve weighting method. The results showed that the integral maximum plasma concentration and area under the curve increased after oral administration of processed Atractylodis Rhizoma.

scholarly journals Determination and Pharmacokinetics of Okanin in Rat Plasma by UltraHigh Performance Liquid Chromatography Coupled with Triple-Quadrupole Tandem Mass Spectrometry

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yurui Shi ◽  
Rongda Chen ◽  
Jing Xie ◽  
Li Li ◽  
Guiming Liu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Oral Administration ◽  
Internal Standard ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Tandem Mass ◽  
Triple Quadrupole ◽  
Ultrahigh Performance Liquid Chromatography

Okanin is a major flavonoid found in Coreopsis tinctoria Nutt., arousing huge interest recently for its considerable biological characteristics including antioxidant, antineurotoxic, and antidiabetic activities. An ultrahigh performance liquid chromatography triple-quadrupole tandem mass spectrometry (UPLC-MS) was successfully used to determine okanin in rat plasma after oral administration of okanin. Bavachalcone acted as an internal standard (IS). By gradient elution, IS and analyte were separated on a C18 column for 7 min at a flow rate of 0.25 mL/min with acetonitrile-0.1% acetic acid mobile phase. The stability, matrix effect, extraction recovery, accuracy, precision, linearity, and selectivity of the method were firstly demonstrated. The major pharmacokinetic parameters of okanin in rat plasma were then measured using the developed UPLC-MS method. An UPLC-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was finally established to obtain the specific and accurate mass of okanin in rat plasma after oral administration, and its proposed fragmentation was further elaborated.

A Validated DBS Method for Quantitation of a Novel Mutant IDH1/2 Inhibitor, Vorasidenib Using 10 μL Mice Blood: Application to a Pharmacokinetic Study in Mice

2020 ◽  
Vol 16 (8) ◽  
pp. 1140-1147
Author(s):  
Sreekanth Dittakavi ◽  
Rakesh Kumar Jat ◽  
Ramesh Mullangi
Keyword(s):  
Oral Administration ◽  
Method Validation ◽  
Pharmacokinetic Study ◽  
Internal Standard ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Bioanalytical Method Validation ◽  
Extraction Solvent ◽  
Validation Parameters ◽  
Intravenous And Oral Administration

Background: Vorasidenib is a pan-IDH inhibitor, undergoing clinical trials for the treatment of acute myeloid leukemia. Methods: In this paper, we present the data of method validation to quantify vorasidenib in the mice blood mice using dried blood spot (DBS) method on LC-MS/MS as per FDA bioanalytical method validation guideline. Using methanol (enriched with internal standard) as an extraction solvent followed by sonication, vorasidenib was extracted from DBS quality control samples, calibration curve samples and pharmacokinetic study samples. Baseline separation of vorasidenib and the IS in a 2.0 μL injected sample was accomplished by delivering 0.2% formic acid and acetonitrile (25:75, v/v) at a constant flowrate (1.00 mL/min) on a C18 column. The total run time was 2.0 min. Using the transition pair of m/z 415.4→260.4 for vorasidenib and m/z 583.1→186.1 for the IS, the quantitation was performed. The method linearity range was 1.00-3008.00 ng/mL. Results: The recovery of vorasidenib ranged between 71.28%-78.14% across the tested concentrations. No matrix effect was seen. Intra- and inter-day precisions were ≤7.23% and intra- and inter-accuracies ranged between 97.1%-107%. Vorasidenib was stable for three freeze/thaw cycles, up to 7 days at room temperature and for one month at -80°C. Following intravenous and oral administration of vorasidenib to mice, it was quantifiable up to 72 h. The oral bioavailability was 51.6%. Conclusions: All the validation parameters met the acceptance criteria as specified in the FDA regulatory guideline. The results suggest that validated DBS method can be used for pharmacokinetic studies in mice to characterize the pharmacokinetic parameters of vorasidenib post intravenous and oral administration.

scholarly journals Simultaneous Determination of Columbianadin and Its Metabolite Columbianetin in Rat Plasma by LC-MS/MS: Application to Pharmacokinetics of Columbianadin after Oral Administration

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Jin Li ◽  
Zhen Li ◽  
Qian Luo ◽  
Chun-Peng Wang ◽  
Jun He ◽  
...  
Keyword(s):  
Oral Administration ◽  
Internal Standard ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Antitumor Activities ◽  
Limit Of Quantification ◽  
Potential Development ◽  
Liquid Chromatography Tandem Mass ◽  
Acetate Aqueous Solution

Columbianadin and its metabolite columbianetin exhibited the anti-inflammatory, analgesic, calcium channel blocking and antitumor activities. To compare the differences between pharmacokinetics of columbianadin and its metabolite columbianetin after oral administration of pure columbianadin and Angelicae Pubescentis Radix (APR) extract, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established and validated to simultaneously determine columbianadin and columbianetin in rat plasma. Two analytes and an internal standard (warfarin) were well separated and determined after liquid-liquid extraction with ethyl acetate. Ammonium acetate aqueous solution (1 mmol/L) and acetonitrile were used as the mobile phase and the flow rate was 0.3 mL/min. The lower limit of quantification (LLOQ) was 0.1 ng/mL for columbianetin and 0.5 ng/mL for columbianadin, respectively. There were significant differences between some pharmacokinetic parameters and bioavailability of columbianadin after oral administration of pure columbianadin and APR extract. The studies on comparative pharmacokinetics of columbianadin were of great use for facilitating the clinical application of columbianadin and were also highly meaningful for the potential development of APR.

scholarly journals Simultaneous Determination of Ten Bioactive Components from Shenling Baizhu San in Rat Plasma by UHPLC-MS/MS: Application to a Comparative Pharmacokinetic Study in Normal and Two Models of Ulcerative Colitis Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Xia Xu ◽  
Weiwei Wang ◽  
Yaxi Chen ◽  
Qiyun Zhang ◽  
Bingtao Li ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Simultaneous Determination ◽  
Internal Standard ◽  
Rat Plasma ◽  
Scientific Basis ◽  
Precipitation Method ◽  
Pharmacokinetic Parameters ◽  
Spleen Deficiency ◽  
Validation Parameters

Shenling Baizhu San, a traditional formula, has a long history of treating spleen asthenic diarrhea by invigorating the spleen and dispelling dampness in China. A rapid and accurate UHPLC-MS/MS method was developed and fully validated for the simultaneous determination of ten active constituents in rat plasma: panaxadiol, ginsenoside Rg1, atractylenolide I, atractylenolide III, pachymic acid, neferine, nuciferine, diosgenin, platycodin D, and isoliquiritigenin. The plasma samples were pretreated by the protein precipitation method with acetonitrile. The analytes and puerarin (internal standard) were determined with high selectivity and sensitivity (LLOQ, 0.31–0.68 ng·mL−1) within 10 minutes. The validation parameters, including intra-/interday precisions, accuracy, recovery, matrix effect, and stability, were within acceptable ranges. The validated method was successfully applied to the pharmacokinetics study of ten components in normal and two rat models of ulcerative colitis (i.e., spleen deficiency with dampness retention-ulcerative colitis (SDDR-UC) rats and pure-ulcerative colitis (P-UC) rats). The pharmacokinetic parameters were significantly different among the three groups of rats. Overall, the absorption of the components was shown as follows: normal group > SDDR-UC group > P-UC group. The study could provide a scientific basis for further studies on pharmacokinetics and clinical differential application of SDDR-UC and P-UC patients.

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