scholarly journals Simultaneous determination and pharmacokinetics studies of five isoflavones in rat plasma by UHPLC-MS/MS after oral administration of Radix Astragali extract

Author(s):  
Jianwei Han ◽  
Wenbo Zhu ◽  
Ling Yu ◽  
Yajun Chen ◽  
Gaosong Wu ◽  
...  

AbstractA rapid, sensitive and convenient method based on ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was developed and validated for the simultaneous quantification of calycosin-7-O-β-d-glucoside (CCSG), ononin, calycosin, (6aR,11aR)-9,10-dimethoxypterocarpan-3-O-β-d-glucopyanoside (DPPG), and 7,2′-dihydroxy-3′,4′-dimethoxyisoflavan-7-O-β-d-glucopyanoside (DIFG) in rat plasma after oral administration of the methanol extraction from Radix Astragali. Theophylline played the role of internal standard (IS). Preparation of plasma samples by liquid-liquid extraction method with ethyl acetate after precipitation of protein with methanol. The analytes were detected with a triple quadrupole tandem mass spectrometery (MS) in multiple reaction monitoring (MRM) mode and a positive ion electrospray ionization (ESI). The method was validated with the concentration ranges of 1.96–62.69 ng/mL for CCSG, 1.70–54.5 ng/mL for ononin, 1.85–59.06 ng/mL for calycosin, 2.14–137.24 ng/mL for DPPG and1.96–125.25 ng/mL for DIFG, respectively. The method had the lower limit of quantification (LLOQ) with 0.49, 0.21, 0.92, 1.07, and 0.98 ng/mL for CCSG, ononin, calycosin, DPPG and DIFG respectively, and the precision less than 10%. The RSD of the accuracy was in the range of −4.35–8.91%. The results may be helpful to provide more accurate references to clinical application of this herb.

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2980 ◽  
Author(s):  
Chengcui Wu ◽  
Meicun Yao ◽  
Wa Li ◽  
Binbin Cui ◽  
Hongrui Dong ◽  
...  

A selective and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of ziyuglycoside I (I), 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester (II), 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester (III), rosamultin (IV), 1β-hydroxyeuscaphic acid (V) and alpinoside (VI) in rats after oral administration of Sanguisorba officinalis L. (S. officinalis) extract. The 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester, rosamultin, 1β-hydroxyeuscaphic acid and alpinoside in rat plasma were the first report in the pharmacokinetics study in the present study. The analytes were quantified using the multiple reaction monitoring (MRM) mode with the electrospray ion source in positive electrospray ionization. Plasma was extracted with ethyl acetate via liquid–liquid extraction. Bifendate was used as internal standard (IS). The current method was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery, matrix effect and stability. The lower limits of quantification of ziyuglycoside I, 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester, rosamultin, 1β-hydroxyeuscaphic acid and alpinoside were 6.1, 4.9, 1.3, 3.8, 1.5 and 5.7 ng/mL, respectively. Intra-day and inter-day precision and the accuracy of the assay were in range from −9.48 to 12.74%. The extraction recoveries of analytes and bifendate (IS) from rat plasma ranged from 77.17% to 92.48%. Six compounds could be rapidly absorbed into blood (Tmax, 0.58–1.58 h), and then eliminated relatively slowly (t1/2, 6.86–11.63 h). The pharmacokinetic results might contribute to further guide the clinical application of S. officinalis.


2020 ◽  
Vol 58 (10) ◽  
pp. 922-928
Author(s):  
Jing Zhang ◽  
Quan Wen ◽  
Meng-ying Zhou ◽  
Chen-cong Zhong ◽  
Yulin Feng ◽  
...  

Abstract Chimonanthi Radix (CR) is widely used in the treatment of influenza in China. Extensive studies revealed that the major bioactive constituents of CR were coumarins. However, pharmacokinetic study of coumarins in CR has not been fully studied. The purpose of this study was to establish a convenient and effective high-performance liquid chromatography–tandem mass spectrometry method that was used to simultaneously determine scopoletin, scopolin and isofraxidin in rat plasma after oral administration of CR extract using xanthotoxin as the internal standard. The chromatographic separation was carried out on a COSMOCORE C18 column (100 × 2 mm, 2.6 μm), using gradient elution with the mobile phase consisting of 0.1% formic acid (A) and acetonitrile (B). Three coumarins and IS were quantified by positive ion electrospray ionization in multiple reaction monitoring mode. The method was fully validated in terms of specificity, accuracy, precision (intra- and inter-day), matrix effect, recovery as well as the stability of the analytes under various conditions. The results could provide further research foundation for anti-influenza mechanism of three coumarins in CR.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Zhen Li ◽  
Yang Li ◽  
Jin Li ◽  
Rui Liu ◽  
Jia Hao ◽  
...  

A sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the toxic and other active components including isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract to rats. Plasma samples were prepared by protein precipitation with methanol. All compounds were separated on a C18 column with gradient elution using acetonitrile and formic acid aqueous solution (0.1%, v/v) as the mobile phase at a flow rate of 0.3 mL/min. The detection of all compounds was accomplished by multiple-reaction monitoring (MRM) in the positive electrospray ionization mode. The LC-MS/MS method exhibited good linearity for five analytes. The lower limit of quantification (LLOQ) was 0.48 ng/mL for scopoletin, periplogenin, and periplocymarin; 2.4 ng/mL for isovanillin and periplocin. The extraction recoveries of all compounds were more than 90% and the RSDs were below 10%. It was found that the absorption of scopoletin and periplocin was rapid in vivo after oral administration of cortex periplocae extract. Furthermore, periplocymarin possessed abundant plasma exposure. The results demonstrated that the validated method was efficiently applied for the pharmacokinetic studies of isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract.


2019 ◽  
Vol 15 (4) ◽  
pp. 371-378
Author(s):  
Jin Wang ◽  
Yang Chu ◽  
Xiao Li ◽  
Navaneethakrishnan Polachi ◽  
Xue-ying Yan ◽  
...  

Background: The Rumex nepalensis Spreng (RNS) is a traditional Chinese medicine containing rich anthraquinones. However, through proper investigation we have found that there were no reports on the pharmacokinetics of RNS extract in rats. </P><P> Objective: We study on the pharmacokinetic behaviors of emodin, chrysophanol and physcion after oral administration of RNS extract in rat to achieve a better understanding of further clinical application and conduct the preparation development of the herb. Methods: In the present study, a sensitive and rapid ultra-fast liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine the three anthraquinones such as chrysophanol, emodin and physcion in rat plasma along with danthron as the internal standard (IS). The analytes and IS were separated on an Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 µm) by using the mobile phase of water with 3 mM ammonium acetate and acetonitrile as gradient elution at a flow rate of 0.4 mL min -1. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by multiple reactions monitoring (MRM) of the transitions at m/z 253.1 → 225.0 for chrysophanol, 269.0 → 224.9 for emodin, 282.7→ 240.0 for physcion and m/z 239.0 → 211.0 for IS. The limit of detection and lower limit of quantification were both 2 ng mL -1 in rat plasma. Results: Good linearity of this method was obtained in the range of 2-1000 ng mL -1 , and the correlation coefficient was greater than 0.990. According to regulatory guidelines, the established method was fully validated, and the results were within acceptable limits. Conclusion: The validated method was successfully applied into a pharmacokinetic study of orally administered RNS extract in rats.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Lian-yun Du ◽  
Tao Jiang ◽  
Kun Wei ◽  
Shuang Zhu ◽  
Yan-long Shen ◽  
...  

A sensitive method has been developed for simultaneous determination of ginsenoside Rh1 (G-Rh1), ginsenoside Rb1 (G-Rb1), ginsenoside Rc (G-Rc), and ginsenoside Rd (G-Rd) in rat plasma of normal and depression model group after oral administration of their solutions by using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-QQQ-MS). The biological samples were prepared by protein precipitation. Ginsenoside Rg3 (G-Rg3) was used as an internal standard (IS). MS analysis was performed under the multiple reaction monitoring (MRM) with electron spray ionization (ESI) operated in the negative mode. The method showed good linearity over a wide concentration range (R2 > 0.999) and obtained lower limits of quantification (LLOQ) of 5 ng/mL. The whole analysis procedure could be completed in as short as 16.5 min. The intraday precisions, interday precisions, and stabilities were less than 10%. The extraction recoveries from rat plasma were exceeded 86.0%. The results indicated that there were significant differences between the two groups on pharmacokinetics parameters; the absorptions of four analytes in the depression group were higher than those in the normal group because the liver metabolism and internal environment of the model rats had been affected.


Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2514 ◽  
Author(s):  
Mingyue Xu ◽  
Zhanling Xu ◽  
Qingxuan Xu ◽  
Hongyue Zhang ◽  
Mingyang Liu ◽  
...  

Xiaoyao Powder (XYP), a common Chinese medicine, comprises eight traditional Chinese herbs and has been widely used clinically to treat liver damage and mental disorders. An ultra-performance liquid chromatography–tandem mass spectrometry method was developed to investigate the pharmacokinetics of 14 compounds (albiflorin, paeoniflorin, ferulic acid, senkyunolide I, quercetin, isoliquiritigenin, atractylenolide III, ligustilide, atractylenolide II, liquiritin, liquiritigenin, saikosaponin c, glycyrrhizic acid, and saikosaponin a) in XYP. Naringenin was used as the internal standard. The compounds were separated using an ACQUITY UPLCTM BEH C18 column (1.7 μm, 50 × 2.1 mm) with a mobile phase consisting of acetonitrile and 0.1% formic acid in water at a flow rate of 0.3 mL/min. Detection was performed on a triple-quadrupole tandem mass spectrometer using multiple reaction monitoring and an electrospray ionization source in both positive and negative ionization modes. All calibration curves exhibited good linearity (r2 > 0.9974) over the measured ranges. The intra- and inter-day precisions were within 12%, and the accuracy ranged from 89.93% to 106.64%. Extraction recovery and matrix effect results were satisfactory. The method was successfully applied in a pharmacokinetic study of the 14 compounds in rat plasma after the oral administration of XYP.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yan Du ◽  
Hongliang Su ◽  
Jie Cao ◽  
Zhiwen Wei ◽  
Yujin Wang ◽  
...  

Male Sprague-Dawley rats (n=18) were randomly divided into three groups: a saline group (20 mL/kg by gavage), a ketamine (KET) group (100 mg/kg by gavage), and a KET (the same routes and doses) combined with levo-tetrahydropalmatine (l-THP; 40 mg/kg by gavage) group (n=6). Blood samples were acquired at different time points after drug administration. A simple and sensitive ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to determine the concentrations of KET and its metabolite, norketamine (NK), in rat plasma. Chromatographic separation was achieved using a BEH C18 column (2.1 mm×50 mm, 1.7 μm) with chlorpheniramine maleate (Chlor-Trimeton) as an internal standard (IS). The initial mobile phase consisted of acetonitrile–water with 0.1% methanoic acid (80 : 20, v/v). The multiple reaction monitoring (MRM) modes of m/z 238.1→m/z 179.1 for KET, m/z 224.1→m/z 207.1 for NK, and m/z 275→m/z 230 for Chlor-Trimeton (IS) were utilized to conduct a quantitative analysis. Calibration curves of KET and NK in rat plasma demonstrated good linearity in the range of 2.5–500 ng/mL (r>0.9994), and the lower limit of quantification (LLOQ) was 2.5 ng/mL for both. Moreover, the intra- and interday precision relative standard deviation (RSD) of KET and NK were less than 4.31% and 6.53%, respectively. The accuracies (relative error) of KET and NK were below -1.41% and -6.07%, respectively. The extraction recoveries of KET and NK were more than 81.23±3.45% and 80.42±4.57%, respectively. This sensitive, rapid, and selective UPLC-MS/MS method was successfully applied to study the pharmacokinetic effects of l-THP on KET after gastric gavage. The results demonstrated that l-THP could increase the bioavailability of KET and promote the metabolism of KET. The results showed that l-THP has pharmacokinetics effects on KET in rat plasma.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Jin Li ◽  
Zhen Li ◽  
Qian Luo ◽  
Chun-Peng Wang ◽  
Jun He ◽  
...  

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.


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