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 Simultaneous determination of two galangin metabolites from Alpinia Officinarum Hance in rat plasma by UF LC-MS/MS and its application in pharmacokinetics study

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11041
Author(s):  
Rangru Liu ◽  
Hailong Li ◽  
Na Wei ◽  
Yinfeng Tan
Keyword(s):  
Analytical Method ◽  
Glucuronic Acid ◽  
Multiple Reaction Monitoring ◽  
Ion Pairs ◽  
Internal Standard ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Alpinia Officinarum ◽  
Negative Electrospray Ionization

Galangin has multiple pharmacological efficacies, such as anti-cancer, anti-inflammation and anti-oxidation. Galangin can be rapidly converted into glucuronidated metabolites in vivo. This study aimed to establish an UFLC-MS/MS analytical method to simultaneously determine the concentrations of two glucuronidated metabolites of galangin, galangin-3-O-β-D-glucuronic acid (GG-1) and galangin-7-O-β-D-glucuronic acid (GG-2) in rat plasma. After oral administration of galangal extract (0.3 g/kg), blood samples were collected from the orbital sinus, then treated by methanol precipitation and further gradient-eluted with Phenomenex Kinetex 2.6 µm XB-C18 column. The mass spectrometer was manipulated in the negative electrospray ionization (ESI) and selected multiple reaction monitoring (MRM) mode for the analytes. The precursor-to-product ion pairs applied for GG-1, GG-2 and chrysin (as the internal standard, IS) were m/z 445.2→269.0, 445.2→268.9 and 253.0→142.9, respectively. The results showed that the linear ranges for both GG-1 and GG-2 were 2.0–2000.0 ng/mL (r2 > 0.995). The inter- and intra-day precision were 89.3%–109.2%, RSD was less than 15%, and the repeatability was good. The recoveries of both metabolites and IS were over 89%, and matrix effect was within 15%. The validated analytical method was further applied to study the pharmacokinetic profiles of GG-1 and GG-2 in vivo. The pharmacokinetic parameters suggested that Tmax of GG-1 was equivalent to that of GG-2, and MRT0-t, t1/2 of GG-2 were a little higher than those of GG-1. Importantly, AUC0-t and Cmax of GG-2 were almost twice as those of GG-1. In short, the validated UFLCMS/MS analytical method was feasible to simultaneously determine two galangin metabolites GG-1 and GG-2 in rat plasma and further analyze in vivo metabolism of galangin.

Determination of JW5473 in Rat Plasma by UPLC-MS/MS and its Application to Pharmacokinetic Study of JW5473

Drug Research ◽  
2019 ◽  
Vol 69 (11) ◽  
pp. 606-611
Author(s):  
Tae Kon Kim
Keyword(s):  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Reversed Phase ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Esi Ms ◽  
Quantitation Limit ◽  
Fraction Absorbed

AbstractA sensitive method for quantitation of JW5473 in rat plasma has been established using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI/MS/MS). Tramadol was used as an internal standard. JW5473 and internal standard in plasma sample was extracted using acetonitrile (protein precipitation). A centrifuged upper layer was then evaporated and reconstituted with the mobile phase of 0.5% formic acid-acetonitrile (40:60, v/v). The reconstituted samples were injected into a C18 reversed-phase column. Using MS/MS in the multiple reaction monitoring (MRM) mode, JW5473 and tramadol were detected without severe interference from rat plasma matrix. JW5473 produced a protonated precursor ion ([M+H]+) at m/z 432.3 and a corresponding product ion at m/z 114.4. And the internal standard produced a protonated precursor ion ([M+H]+) at m/z 264.4 and a corresponding product ion at m/z 58.1. Detection of JW5473 in human plasma by the UPLC-ESI/MS/MS method was accurate and precise with a quantitation limit of 1.0 ng/mL. The validation, reproducibility, stability, and recovery of the method were evaluated. The method has been successfully applied to pharmacokinetic studies of JW5473 in rat plasma. Pharmacokinetic parameters of JW5473 was evaluated after intravenous (i. v.; at doses of 15 mg/kg) and oral (p.o.; at doses of 30 mg/kg) administration of JW5473 in rats. After p.o. administration (30 mg/kg) of JW5473, F (Fraction absorbed) value was approximately 70.5%.

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.

Simultaneous Determination of Three Alkaloids in Wutou Decoction in Rat Plasma Via the UPLC–MS/MS Method and its Application in Pharmacokinetic Study

2020 ◽  
Vol 16 (5) ◽  
pp. 558-563
Author(s):  
WU Jian ◽  
JI Yu-bin ◽  
Liu Ying-jie ◽  
XU Ying ◽  
Zheng Wei ◽  
...  
Keyword(s):  
Electrospray Ionization ◽  
Pharmacokinetic Study ◽  
Multiple Reaction Monitoring ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Intragastric Administration ◽  
Highly Sensitive ◽  
Pharmacokinetic Properties

Introduction: Wutou decoction has been wildly applied for the treatment of RA in China for several thousand years. Methods: This study aims to develop a highly sensitive and specific ultra performance liquid chromatography coupled with tandem mass spectrometry and electrospray ionization (UPLC-ESI-MS/MS) method to explore the pharmacokinetic properties of three representative bioactive alkaloids after intragastric administration of Wutou decoction in rats. Chromatographic separation was performed on a C18 column under the Multiple Reaction Monitoring (MRM) in the positive electrospray ionization (ESI) mode. The pharmacokinetic parameters were evaluated by software DAS 3. 0. Results: The validation of the method was achieved in accordance with the FDA guidelines. The results of pharmacokinetic study showed that the in vivo concentrations of benzoylmesaconine and benzoylhypaconine were significantly higher than benzoylaconine. Our PK results showed that these three compounds were quickly absorbed after the administration of Wutou decoction, and Tmax ranged from 30 min to 45 min. Conclusion: The results of pharmacokinetic study showed that the in vivo concentrations of benzoylmesaconine and benzoylhypaconine were significantly higher than benzoylaconine. There were also similar pharmacokinetic behaviors observed among BAC, BHA, and BMA after oral administration of WTD.

scholarly journals Effect of Citrus suavissima Hort. ex Tanaka on pharmacokinetics of erlotinib in rat plasma by UPLC-MS/MS

2020 ◽  
Author(s):  
Jinzhao Yang ◽  
Huamin Liu ◽  
Yuan Cai ◽  
Yazhen Wu ◽  
Xiaoxin Xu ◽  
...  
Keyword(s):  
Oral Administration ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Physiological Saline ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Control Group ◽  
Sprague Dawley ◽  
Physiological Saline Solution

AbstractTwelve Sprague-Dawley rats were randomly divided into two groups: Citrus suavissima Hort. ex Tanaka group and control group (n = 6). The rats in Citrus suavissima Hort. ex Tanaka group were given Citrus suavissima Hort. ex Tanaka juices (1 mL/100 g) by oral administration each day, continued for 14 days; the rats in control group were given Stroke-physiological saline solution (1 mL/100 g) by oral administration each day, continued for 14 days. The rats of these two groups were given a single oral administration of erlotinib (20 mg/kg) on the 15th day. After blood sampling at different time points and processing, the concentrations of erlotinib in rat plasma were determined by the established ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. Chromatographic separation was achieved using a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with erlotinib-d6 as an internal standard (IS). The initial mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) with gradient elution. Multiple reaction monitoring (MRM) modes were utilized to conduct quantitative analysis. The sensitive, rapid and selective UPLC-MS/MS method was successfully applied to analyse the effect of Citrus suavissima Hort. ex Tanaka on pharmacokinetics of erlotinib in rat plasma. There were no significant differences in AUC(0−t), t1/2, Tmax, CL, Cmax between the two groups (P > 0.05). While MRT(0−t) was decreased (P < 0.05) in Citrus suavissima Hort. ex Tanaka group, compared to the control group. It showed that Citrus suavissima Hort. ex Tanaka could not affect the metabolism of erlotinib.

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 An LC-MS/MS Method for Simultaneous Determination of the Toxic and Active Components of Cortex Periplocae in Rat Plasma and Application to a Pharmacokinetic Study

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Zhen Li ◽  
Yang Li ◽  
Jin Li ◽  
Rui Liu ◽  
Jia Hao ◽  
...  
Keyword(s):  
Oral Administration ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Simple Liquid ◽  
Active Components ◽  
Limit Of Quantification ◽  
Liquid Chromatography Tandem Mass

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.

scholarly journals Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir following Intravenous and Oral Administrations in Rats: A study Involving in vivo corneal Uptake of Acyclovir following Oral Dosing

2009 ◽  
Vol 1 ◽  
pp. OED.S2857 ◽  
Author(s):  
Ravi S. Talluri ◽  
Ripal Gaudana ◽  
Sudharshan Hariharan ◽  
Ashim K. Mitra
Keyword(s):  
Oral Administration ◽  
Oral Absorption ◽  
Area Under The Curve ◽  
Systemic Circulation ◽  
Precipitation Method ◽  
Drug Candidate ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Uptake Studies

Objective To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV) in rats. Methods Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV), L-valine-D-valine-acyclovir (LDACV) and D-valine-L-valine acyclovir (DLACV) prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results Following i.v. administration, the area under the curve (AUC) in μM*min of generated ACV was in the order of LACV > LDACV > DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 μM*min, respectively. DLACV exhibited poor oral absorption. Cmax (μM) and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.

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

2021 ◽  
Author(s):  
Jianwei Han ◽  
Wenbo Zhu ◽  
Ling Yu ◽  
Yajun Chen ◽  
Gaosong Wu ◽  
...  
Keyword(s):  
Oral Administration ◽  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
Tandem Mass ◽  
Radix Astragali ◽  
Limit Of Quantification ◽  
Liquid Chromatography Tandem Mass ◽  
Mass Spectrometery

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.

scholarly journals Pharmacokinetic UPLC–MS/MS studies on byakangelicol after oral and intravenous administration to rats

2020 ◽  
Vol 32 (1) ◽  
pp. 49-52
Author(s):  
Xi Bao ◽  
Bingge Huang ◽  
Yiting Mao ◽  
Zhiguang Zhang ◽  
Yunfang Zhou ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Multiple Reaction Monitoring ◽  
A549 Cells ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Absolute Bioavailability ◽  
Dependent Manner ◽  
Limit Of Quantitation ◽  
Intravenous And Oral Administration

Byakangelicol is one of coumarins from Baizhi and has been shown to inhibit the release of PGE2 from human lung epithelial A549 cells in a dose-dependent manner. A sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and full validated for the quantification of byakangelicol in rat plasma. The pharmacokinetics of byakangelicol after both intravenous (5 mg/kg) and oral (15 mg/kg) administrations were studied. Chromatographic separation was performed on an ultra-performance liquid chromatography ethylene bridged hybrid (UPLC BEH) C18 column with acetonitrile and 0.1% formic acid as the mobile phase at a flow rate of 0.4 mL/min; fargesin was used as the internal standard (IS). The following quantitative analysis of byakangelicol was utilized in the multiple reaction monitoring mode. The samples were extracted from rat plasma via protein precipitation using acetonitrile. In the concentration range of 1–2000 ng/mL, the method correlated linearity (r > 0.995) with a lower limit of quantitation (LLOQ) of 1 ng/mL. Intra-day precision was less than 11%, and inter-day precision was less than 12%. The accuracy was between 92.0% and 108.7%, the recovery was better than 89.6%, and the matrix effect was between 85.9% and 98.6%. The method was successfully applied to a pharmacokinetic study of byakangelicol after intravenous and oral administration, and the absolute bioavailability was 3.6%.

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