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.

Simultaneous Determination of Kirenol, Rosmarinic Acid and Caffeic Acid in Rat Plasma and Pharmacokinetic Study After Oral Administration of the Extract of Manxingshizhen Preparation by UPLC-MS/MS

2018 ◽  
Vol 15 (1) ◽  
pp. 74-81 ◽  
Author(s):  
Shuo Sun ◽  
Xue Zhang ◽  
Linda Luo ◽  
Ping Wang ◽  
Mengxuan Bai ◽  
...  
Keyword(s):  
Oral Administration ◽  
Electrospray Ionization ◽  
Simultaneous Determination ◽  
Caffeic Acid ◽  
Pharmacokinetic Study ◽  
Rosmarinic Acid ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Tandem Mass Spectrometric

Introduction: A rapid, sensitive and convenient ultra-performance liquid chromatography with tandem mass spectrometric detection (UPLC-MS/MS) method has been validated and applied to the simultaneous determination of kirenol, rosmarinic acid and caffeic acid after oral administration of the extract of Manxingshizhen preparation in rat plasma. Materials and Methods: Puerarin was selected as the internal standard (IS). The plasma sample preparation was pretreated by liquid-liquid extraction of the mixture with ethyl acetate. All analytes were simultaneously detected in multiple reaction monitoring (MRM) mode via both the positive electrospray ionization (ESI+) and negative electrospray ionization (ESI). In the experiment, all calibration curves revealed good linearity (r > 0.999). The LLOQ were between 0.80-2.00 ng/mL, respectively. Besides, the intra-day and inter-day precision ranged from 6.4 to 13.8%, respectively. Moreover, the accuracy was within - 11.4% and 12.8% for all the QC levels of all analytes. The extraction recoveries of the analytes and IS in plasma at three concentration levels ranged from 88.5 to 103.2%, moreover, the matrix effects of all the analytes and the IS were found to be satisfied with the acceptable range of 89.8%-101.7%. Meanwhile, the RSD values of stability met the requirement of not more than 15%. Furthermore, the pharmacokinetic parameters of three compounds were analyzed using concentrationtime profiles. Conclusion and Results: Plasma concentrations of the three compounds were determined up to 24 h after oral administration, and their pharmacokinetic parameters were in agreement with previous studies. The validated method was successfully applied in a pharmacokinetic study in rat plasma after oral administration of Manxingshizhen preparation.

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 Development of an UPLC–MS/MS assay to determine psoralidin in rat plasma and its application in a pharmacokinetic study after intragastric administration

2020 ◽  
Vol 32 (4) ◽  
pp. 215-218
Author(s):  
Feng Feng ◽  
Xiunan Jiang ◽  
Jieying Qiu ◽  
Hongyu Wu ◽  
Xiaojun Cai ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Internal Standard ◽  
Apparent Volume ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Intragastric Administration ◽  
Rat Tissues ◽  
Pharmacokinetic Characteristic

Psoralidin has a variety of pharmacological activities, such as anti-tumor, anti-depressant, and anti-inflammatory activities. This study aims at developing a rapid ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method to determine psoralidin in rat plasma and studying the pharmacokinetic characteristic of psoralidin after intragastric administration of 20 and 40 mg/kg. Alpinetin was used as an internal standard (IS), and the plasma samples were precipitated with acetonitrile. The calibration curves were linear over the range of 0.2–250 ng/mL (R2 = 0.993). The pharmacokinetic parameters were calculated by DAS 3.0. Half-life (t1/2) was 7.2 ± 0.97 h and 7.1 ± 0.27 h for different dosages, respectively. Tmax was 4.2 ± 1.1 h and 4.0 ± 1.1 h for different dosages, respectively. Apparent volume of distribution (Vd) for different dosages was 630.1 ± 168.8 and 600.1 ± 138.8 L/kg, respectively. Clearance (CL) was 105.6 ± 29.2 and 100.6 ± 22.2 L/h/kg for different dosages, indicating that psoralidin was mainly distributed in rat tissues. The pharmacokinetic study provided important information for further clinical application in the treatment of cancer and osteoporosis.

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 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 Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS method

2021 ◽  
Vol 71 (3) ◽  
pp. 415-428
Author(s):  
Sai-Jie Zuo ◽  
Xiao-Liang Cheng ◽  
Dong-Zheng Liu ◽  
Wei-Yi Feng ◽  
Yong-Xiao Cao ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Growth Factor Receptor ◽  
Internal Standard ◽  
Gradient Elution ◽  
Storage Conditions ◽  
Rat Plasma ◽  
Selected Reaction Monitoring ◽  
Pharmacokinetic Parameters ◽  
Egfr Inhibitor ◽  
Reliable Quantification

Abstract1-(4-(Pyrrolidin-1-yl-methyl)phenyl)-3-(4-((3-(trifluoromethyl) phenyl)amino)quinazolin-6-yl)urea (ZCJ14), a novel epidermal growth factor receptor (EGFR) inhibitor, with diarylurea moiety, displays anticancer effect. In the present study, an LCMS/MS method was established to determine the concentration of ZCJ14 in rat plasma. Furthermore, the method was applied to investigate the pharmacokinetic characteristics of ZCJ14. Chromatographic separation of ZCJ14 and internal standard (IS) [1-phenyl-3-(4-((3-(trifluoromethyl)phenyl)amino) quinazolin-6-yl)urea] was accomplished by gradient elution using the Kromasil C18 column. The selected reaction monitoring transitions were performed at m/z 507.24→436.18 and 424.13→330.96 for ZCJ14 and IS, resp. The established method was linear over the concentration range of 10–1000 ng mL−1. The intra- and inter-day precisions were < 11.0 % (except for LLOQ which was up to 14.3 %) and the respective accuracies were within the range of 87.5–99.0 %. The extraction recovery and matrix effect were within the range of 88.4–104.5 % and 87.3–109.9 %, resp. ZCJ14 was stable under all storage conditions. The validated method was successfully applied to the pharmacokinetic study of ZCJ14 in rats, and the pharmacokinetic parameters have been determined. The oral bioavailability of ZCJ14 was found to be 46.1 %. Overall, this accurate and reliable quantification method might be useful for other diarylurea moiety-containing drugs.

scholarly journals Pharmacokinetic Study of Safrole and Methyl Eugenol after Oral Administration of the Essential Oil Extracts of Asarum in Rats by GC-MS

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yuqi Fan ◽  
Dongyue Yang ◽  
Xuhua Huang ◽  
Guangzhe Yao ◽  
Wei Wang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Pharmacokinetic Study ◽  
Inflammatory Diseases ◽  
Rat Plasma ◽  
Clinical Applications ◽  
Methyl Eugenol ◽  
Pharmacokinetic Parameters ◽  
Selected Ion Monitoring ◽  
Processed Products ◽  
Gas Chromatography Mass Spectroscopy

Asarum is a traditional medicine and has been widely used as remedies for inflammatory diseases, toothache, headache, local anesthesia, and aphthous stomatitis in China, Japan, and Korea. Our previous research found that safrole and methyl eugenol were vital compounds that contribute to distinguish the different species and raw Asarum and its processed products apart. The pharmacokinetics of safrole and methyl eugenol after oral administration of Asarum extract has not been reported yet. In this study, a rapid and simple gas chromatography–mass spectroscopy (GC–MS) method that has a complete run time of only 4.5 min was developed and validated for the simultaneous determination and pharmacokinetic study of safrole and methyl eugenol in rat plasma after administration of Asarum extracts. The chromatographic separation was realized on a DB-17 column ( 30   m × 0.25   mm × 0.25   μ m ). And detection was carried out under selected ion monitoring (SIM) mode. Plasma samples were pretreated by n -hexane. The pharmacokinetic parameters provided by this study will be beneficial for further developments and clinical applications of Asarum.

Sign in / Sign up

Export Citation Format

Share Document